Biomedical subjects

H Kwon

Publications and source records attributed to H Kwon.

At least 19 recordsLinked to original sources

PubMed2006

A novel mutation in the mitochondrial tRNA(Ser(AGY)) gene associated with mitochondrial myopathy, encephalopathy, and complex I deficiency.

PURPOSE: To identify molecular defects in a girl with clinical features of MELAS (mitochondrial encephalomyopathy and lactic acidosis) and MERRF (ragged-red fibres) syndromes. METHODS: The enzyme complex activities of the mitochondrial respiratory chain were assayed. Temporal temperature gradient gel electrophoresis was used to scan the entire mitochondrial genome for unknown mitochondrial DNA (mtDNA) alterations, which were then identified by direct DNA sequencing. RESULTS: A novel heteroplasmic mtDNA mutation, G12207A, in the tRNA(Ser(AGY)) gene was identified in the patient who had a history of developmental delay, feeding difficulty, lesions within her basal ganglia, cerebral atrophy, proximal muscle weakness, increased blood lactate, liver dysfunction, and fatty infiltration of her muscle. Muscle biopsy revealed ragged red fibres and pleomorphic mitochondria. Study of skeletal muscle mitochondria revealed complex I deficiency associated with mitochondrial proliferation. Real time quantitative PCR analysis showed elevated mtDNA content, 2.5 times higher than normal. The tRNA(Ser(AGY)) mutation was found in heteroplasmic state (92%) in the patient's skeletal muscle. It was not present in her unaffected mother's blood or in 200 healthy controls. This mutation occurs at the first nucleotide of the 5' end of tRNA, which is involved in the formation of the stem region of the amino acid acceptor arm. Mutation at this position may affect processing of the precursor RNA, the stability and amino acid charging efficiency of the tRNA, and overall efficiency of protein translation. CONCLUSION: This case underscores the importance of comprehensive mutational analysis of the entire mitochondrial genome when a mtDNA defect is strongly suggested.

Base Sequence↗

PubMed2005

Estimation of daily exposure to 4-hydroxy-2-alkenals in Korean foods containing n-3 and n-6 polyunsaturated fatty acids.

4-Hydroxy-2-alkenals are cytotoxic aldehydes generated from the oxidation of n-3 and n-6 polyunsaturated fatty acids. The compounds have shown various biological effects via Schiff base adducts or Michael addition adducts at levels higher than physiological ones. To assess human exposure to 4-hydroxy-2-alkenals in the diet, 4-hydroxy-2-alkenals in vegetable oils, fish and shellfish were monitored using GC/MS/SIM. 2001 National Health and Nutrition Survey (2002) data were employed for the dietary intake pattern. The Korean daily exposure to 4-hydroxy-2-alkenals, excluding a possible one from fried food, was 4.3 microg day-1, constituted of 1.6 microg 4-hydroxy-2-hexenal (HHE) and 2.7 microg 4-hydroxy-2-nonenal (HNE). It was calculated that Koreans could be additionally exposed to more than 11.8 microg day-1 4-hydroxy-2-alkenal from fried foods. Thus, the combined exposure would be 16.1 microg day-1, which corresponds to 0.3 microg kg-1 body weight day-1 for a 60 kg Korean adult. In spite of the biological toxicity of 4-hydroxy-2-alkenals, the risk for human could not be quantified due to the lack of a virtually safe dose of the compounds. However, considering the basal level of 4-hydroxy-2-alkenals in many tissues, the present value from the diet may not pose a significant risk for human health.

Adult↗

PubMed2005

Removal of endocrine disruptors using homogeneous metal catalyst combined with nanofiltration membrane.

Chemicals that are known or suspected of being endocrine disrupting chemicals (EDCs) have received increased attention over the past decade for their potential presence in drinking water sources. This study focuses on the development of a hybrid system that combines the advantages of nanofiltration (NF) and homogeneous catalytic oxidation, which include compactness, operational facilitation, high treatment efficiency, and selective reaction capability. Iron(lll)-tetrasulfophthalocyanine (Fe-TsPc) was employed as a homogeneous metal catalyst to degrade bisphenol-A (BPA), a representative EDC. The treatment efficiency of BPA as well as operational characteristics of the hybrid system was investigated to examine the applicability of this technique to decrease the concentration of EDCs in drinking water. Fe-TsPc homogeneous catalyst revealed a remarkable activity in degrading BPA under acidic condition. The high rejection of Fe-TsPc catalyst in the feed stream by the membrane for its large molecular weight (976 Da) and functional group (SO3(-) X4) allowed the continuous use of the catalyst for BPA oxidation reaction. The NF with Fe-TsPc/H2O2 hybrid system turned out to have higher BPA treatment efficiency comparing with the NF-only system since the hybrid system reduced BPA concentration in the feed stream by catalytic destruction of BPA as well as it mitigated concentration polarization on the surface of the membrane.

Benzhydryl Compounds↗

PubMed2004

Optimal sensor distribution for measuring the tangential field components in MCG.

We discuss the optimal arrangement of detectors for a 52-channel magnetocardiogram (MCG) system measuring tangential components of the cardiac magnetic fields. Nowadays, most MCG instruments are designed to cover the whole heart area to maximize the information available from the myocardial magnetic field in a simultaneous measurement. In such a system, detectors should be spread over a sufficiently wide area. However, an increased diameter of the cooling dewar will result in more heat-loss and higher production and maintenance costs. Therefore, we reviewed the spatial sampling theory to determine the proper interval between detectors, and we decided on the number of channels to cover the whole heart area. In order to fit the detector array on the cylindrical dewar economically, we removed the detectors at the corners of the square array. Through simulations using the confidence region method, we verified that our design of the detector array is enough to obtain adequate information from the heart. Simulations also suggested that tangential-component MCG measurement can localize deep current dipoles better than normal-component measurement with the same confidence volume; therefore, we conclude that measurement of the tangential component is more suitable to an MCG system than the normal component.

Body Surface Potential Mapping↗

PubMed2004

Auditory evoked field responses in the left hemisphere to morphosyntactic violations in Korean sentence.

To investigate multiple cortical regions associated with syntactic processes at the sentence level, auditory evoked field responses to morphosyntactic violations were measured over the left hemisphere of seven subjects. Subjects were asked to judge the acceptability of the final verb in verb-ending Korean sentence. Measured field data were transformed to the fields that would be detected on a standard sensing plane and averaged across subjects in different violation conditions. In the grand average data, we found distinct features at latencies of 400 ms and 600 ms, which seem to be specific to morphosyntactic processes. Equivalent current dipoles (ECDs) plotted on a standard brain indicate the inferior frontal region and the superior temporal gyrus for 400 ms component, and the middle temporal gyrus for 600 ms component. Our MEG study localized the distinct cortical regions involved in syntactic processes, which may be reflected in LAN and P600 of ERP.

Acoustic Stimulation↗

PubMed2004

Averaging algorithm based on data statistics in magnetocardiography.

An algorithm for automatic averaging of a magnetocardiogram (MCG) is described. Due to the relatively low signal-to-noise ratio in the MCG, the measured MCG data are often averaged to be analyzed. Generally, R-peaks are used as trigger points, which become anchors for superposition and we can obtain an averaged epoch eventually. However, we have to determine several parameters, such as the threshold magnitude for recognizing R-peak, the time-period of the epoch window, and which channel has dominant R-peaks. In order to determine these parameters automatically, we utilize the magnitude histogram of the root-mean-square waveform of all the channels. We can determine the threshold magnitudes for recognizing R-peaks and T-peaks, respectively, by using the characteristic distribution of the MCG signal histogram. Peak detection procedure using these thresholds records all the locations of the R-peaks and T-peaks, thus we get the average latencies of the R-T intervals and the R-R intervals. From these latencies, we estimate the full width of the epoch window. By adding a routine for processing double R-peaks, our algorithm could conduct the MCG averaging sequence fully automatically. The algorithm has been tested on recordings of 40 normal subjects and 15 patients suffering from myocardial ischemia, and we conclude that this algorithm reliably performs the averaging sequence. The MCG recordings are measured by our 62-channel planar gradiometer system in a magnetically shielded room.

Algorithms↗

PubMed2003

Simultaneous determination of 4-hydroxy-2-alkenals, lipid peroxidation toxic products.

Lipid peroxidation has been associated with cell injury and possible carcinogenecity, for the products can damage cellular membrane and DNA. Among the products formed from lipid peroxidation, 4-hydroxy-2-alkenals are the major components and have been suggested to play a role in cellular toxicity. However, the difficulties of the quantification due to their strong reactivity during laboratory procedures hinder the exposure measurement of the compounds. A novel detection method based on the conversion of 4-hydroxy-2-alkenals to stable diols and to subsequent ortho-esters has been developed. Simultaneous detection in a sensitive single-ion monitoring mode by GC/MS was carried out, monitoring m/z 129, which was the common fragment ion for the ortho-esters derived from 4-hydroxy-2-alkenals. The proposed method was used to quantify 4-hydroxy-2-nonenal in oils and in oxidized arachidonic acid.

Aldehydes↗

PubMed2002

Localization accuracy of single current dipoles from tangential components of auditory evoked fields.

We investigated the localization accuracy of single current dipoles from the tangential components of auditory evoked fields. The tangential fields were measured using planar gradiometers arranged in a way so as to detect two orthogonal field components parallel to a flat plane. Field responses to 1 kHz pure tones were recorded and equivalent current dipoles (ECDs) of N1m peak were estimated based on a locally fitted spherical conductor model. As a measure of localization accuracy, the standard deviation of the coordinates of the ECDs of N1m was obtained from repeated measurements for one subject. The estimated ECDs had a standard deviation of 5.5 mm and their mean location was at the supratemporal plane in the sylvian fissure on the MR image of the subject. In order to investigate the contribution of various errors to the localization accuracy, simulations using a sphere model and experiments using a realistically shaped skull phantom were performed. It was found that the background noise, which consisted of instrumental noise and spontaneous brain fields, was the main source of the errors that could explain the observed standard deviation. Further, the amount of systematic error was much less than the standard deviation due to the background noise. These results suggest that the volume currents in a non-spherical conductor shape such as the temporal region do not produce substantial errors in the localization of current dipoles from tangential components of auditory evoked fields.

Acoustic Stimulation↗

PubMed2002

Neural basis of protracted developmental changes in visuo-spatial working memory.

Developmental studies have shown that visuo-spatial working memory (VSWM) performance improves throughout childhood and adolescence into young adulthood. The neural basis of this protracted development is poorly understood. In this study, we used functional MRI (fMRI) to examine VSWM function in children, adolescents, and young adults, ages 7-22. Subjects performed a 2-back VSWM experiment that required dynamic storage and manipulation of spatial information. Accuracy and response latency on the VSWM task improved gradually, extending into young adulthood. Age-related increases in brain activation were observed in focal regions of the left and right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex (including Broca's area), left premotor cortex, and left and right posterior parietal cortex. Multiple regression analysis was used to examine the relative contributions of age, accuracy, and response latency on activation. Our analysis showed that age was the most significant predictor of activation in these brain regions. These findings provide strong evidence for a process of protracted functional maturation of bilateral fronto-parietal neural networks involved in VSWM development. At least two neural systems involved in VSWM mature together: (i) a right hemisphere visuo-spatial attentional system, and (ii) a left hemisphere phonological storage and rehearsal system. These observations suggest that visually and verbally mediated mnemonic processes, and their neural representations, develop concurrently during childhood and adolescence and into young adulthood.

Adolescent↗

PubMed2001

Temporal and spatial expression of neurotrophins and their receptors during male germ cell development.

Spermatogenesis is a stepwise cellular differentiation process involving proliferation and commitment to differentiate in spermatogonia, meiosis in spermatocytes, and morphological changes in round spermatids. The whole process is regulated by intercellular communication between the germ cells and the supporting cells. In order to investigate whether neurotrophin family and their receptors contribute to the intercellular communication, we examined the expression of neurotrophins and their receptors in testis during spermatogenesis. One of neurotrophin family, NT-3 was expressed in spermatocytes and spermatogonia while its high affinity receptor, TrkC was found mainly in late spermatids and their low affinity receptor, TrkA in spermatocytes and round spermatids. On the other hand, BDNF immunoreactivity was found in Sertoli cells while its high affinity receptor, TrkB was found in spermatogonia. The temporally and spatially regulated expression of neurotrophins, NT-3 and BDNF, and their receptors, TrkC and TrkB, during male germ cell development suggests that neurotrophins play as the paracrine factors in the intercellular communication between the germ cells and the supporting somatic cells to control germ cell development.

Animals↗

PubMed2001

Generation of the dominant-negative mutant of hArpNbeta: a component of human SWI/SNF chromatin remodeling complex.

hArpNbeta, an actin-related protein located within the nucleus, is a subunit of the human SWI/SNF chromatin remodeling complex. hArpNbeta has been proposed to regulate the assembly and activity of the hSWI/SNF complex. Sequence comparisons of the potential ArpN homologs with beta-actin showed that the ArpNs have the divergent subdomains Ib and IIb in addition to the unique N-terminal short insert, MS(G/A)-(V/L)YGG. Since the proposed function of hArpNbeta requires more than two distinct but concurrently operating surfaces, we examined whether the disruption of one operating surface of hArpNbeta results in dominant-negative phenotype. When overexpressed in HeLa or 293T cells, the subdomain Ib or IIb hybrids, in which the subdomain Ib or IIb of hArpNbeta was replaced with that of beta-actin, respectively, showed no effect on cell survival. On the other hand, the overexpression of the N-terminal deletion mutant of hArpNbeta resulted in cell death probably through apoptotic process. These results indicate that the proper function of hArpNbeta is essential for cell survival in human cells. Furthermore, they suggests the possibility that the N-terminal short sequence is indispensable for the chromatin remodeling activity or the assembly of the hSWI/SNF complex after the binding of hArpNbeta with functionally essential partner proteins.

Actins↗

PubMed2001

Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF-related apoptosis-inducing ligand expression.

The NF-kappaB family of transcription factors functions broadly in the host control of immunoregulatory gene expression, inflammation, and apoptosis. Using Jurkat T cells engineered to inducibly express a transdominant repressor of IkappaBalpha, we examined the role of NF-kappaB in the regulation of cytokine and apoptotic gene expression. In this T cell model, as well as in primary T lymphocytes, expression of TNF-related apoptosis-inducing ligand (TRAIL) apoptotic signaling protein was dramatically down-regulated by inhibition of NF-kappaB binding activity. TRAIL acts through membrane death receptors to induce apoptosis of activated T lymphocytes and can be up-regulated by a variety of physiological and pharmacological inducers. However, regulation of TRAIL gene expression has not been defined. Treatment with TCR mimetics (PMA/ionomycin, PHA, and anti-CD3/CD28 Abs) resulted in a rapid increase in the expression of TRAIL mRNA and cell surface TRAIL protein. Induction of the transdominant repressor of IkappaBalpha dramatically down-regulated surface expression of TRAIL, indicating an essential role for NF-kappaB in the regulation of TRAIL. The induced expression of TRAIL was linked to a c-Rel binding site in the proximal TRAIL promoter at position -256 to -265; mutation of this site or an adjacent kappaB site resulted in a complete loss of the inducibility of the TRAIL promoter. The regulation of TRAIL expression by NF-kappaB may represent a general mechanism that contributes to the control of TRAIL-mediated apoptosis in T lymphocytes.

Amino Acid Substitution↗

PubMed2001

Induction of apoptosis in p53-deficient human hepatoma cell line by wild-type p53 gene transduction: inhibition by antioxidant.

We investigated the role of wild-type (wt)-p53 as an inducer of apoptotic cell death in human hepatoma cell lines. Following the retrovirus-mediated transduction of the wt-p53 gene, Hep3B cells lacking the endogenous p53 expression began to die through apoptosis in 4 h. They showed a maximal apoptotic death at 12 h, whereas HepG2 cells expressing endogenous p53 did not. However, the transduction of the wt-p53 gene elicited growth suppression of both Hep3B and HepG2 cells. P21(WAF1/CIP1), a p53-inducible cell cycle inhibitor, was induced, not only in Hep3B cells undergoing apoptosis, but also in HepG2 cells. The kinetics of the p21(WAF1/CIP1) induction, DNA fragmentation, and growth suppression of the Hep3B cells showed that DNA fragmentation and growth suppression progressed rapidly following p21(WAF1/CIP1) accumulation. N-acetyl-cysteine or glutathione, potent antioxidants, strongly inhibited the DNA fragmentation, but did not reduce the elevated level of p21(WAF1/CIP1). These findings suggested that p21(WAF1/CIP1) was not a critical mediator for the execution of p53-mediated apoptosis, although it contributed to the growth inhibition of cells undergoing apoptosis. Furthermore, p53-mediated apoptosis could be repressed by antioxidants.

Acetylcysteine↗

PubMed2001

Effect of endplate conditions and bone mineral density on the compressive strength of the graft-endplate interface in anterior cervical spine fusion.

STUDY DESIGN: Destructive compression tests and finite element analyses were conducted to investigate the biomechanical strength at the graft-endplate interface in anterior cervical fusion. OBJECTIVES: To investigate the effect of endplate thickness, endplate holes, and bone mineral density of the vertebral body on the biomechanical strength of the endplate-graft interface in an anterior interbody fusion of the cervical spine. SUMMARY OF BACKGROUND: Subsidence of the graft into the vertebral body is a well-known complication in anterior cervical fusion. However, there is no information in the literature regarding the compressive strength of the graft-endplate interface in relation to the endplate thickness, holes in the endplate, and bone mineral density of the vertebral body. METHODS: Biomechanical destructive compression tests and finite element analyses were performed in this study. Cervical vertebral bodies (C3-C7) isolated from seven cadaveric cervical spines (age at death 69-86 years, mean 79 years) were used for compression tests. Bone mineral density of each vertebral body was measured using a dual energy radiograph absorptiometry unit. Endplate thickness was measured using three coronal computed tomography images of the middle portion of the vertebral body obtained using a computer-assisted imaging analysis. Then each vertebral body was cut into halves through the horizontal plane. A total of 54 specimens, consisting of one endplate and half of the vertebral body, were obtained after excluding eight vertebrae with gross pathology on plain radiograph. Specimens were assigned to one of three groups with different endplate conditions (Group I, intact; Group II, partial removal; and Group III, complete removal) so that group mean bone mineral density became similar. Each endplate was slowly compressed until failure using an 8-mm-diameter metal indenter, and the load to failure was determined as a maximum force on a recorded force-displacement curve. The effect on the strength of the graft-endplate interface of various hole patterns in the endplate was studied using a finite element technique. The simulatedhole patterns included the following: one large central hole, two lateral holes, two holes in the anterior and posterior portion of the endplate, and four holes evenly distributed from the center of the endplate. Stress distribution in the endplate was predicted in response to an axial compressive force of 110 N, and the elements with von Mises stress greater than 4.0 MPa were determined as failed. RESULTS: The endplate thickness and bone mineral density were similar at all cervical levels, and the superior and inferior endplates had similar thickness at all cervical levels. There was no significant association between bone mineral density and endplate thickness. Load to failure was found to have a significant association with bone mineral density but not with endplate thickness. However, load to failure tends to decrease with incremental removal of the endplate, and load to failure of the specimens with an intact endplate was significantly greater than that of the specimens with no endplate. Finite element model predictions showed significant influence of the hole pattern on the fraction of the upper endplate exposed to fracture stress. A large hole was predicted to be more effective than the other patterns at distributing a compressive load across the remaining area and thus minimizing the potential fracture area. CONCLUSION: Results of this study suggest that it is important to preserve the endplate as much as possible to prevent graft subsidence into the vertebral body, particularly in patients with poor bone quality. It is preferable to make one central hole rather than multiple smaller holes in the endplate for vascularity of the bone graft because it reduces the surface area exposed to fracture stresses.

Aged↗

PubMed2001

Activation of the I kappa B alpha kinase (IKK) complex by double-stranded RNA-binding defective and catalytic inactive mutants of the interferon-inducible protein kinase PKR.

The interferon (IFN)-inducible double stranded (ds) RNA-activated protein kinase PKR plays an important role in protein synthesis by modulating the phosphorylation of the alpha-subunit of eukaryotic initiation fact 2 (eIF-2 alpha). In addition to translational control, PKR has been implicated in several signaling pathways leading to gene transcription. For example, PKR induces I kappa B alpha kinase (IKK) activity and I kappa B alpha phosphorylation leading to the induction of NF-kappa B-mediated gene transcription. Recent findings suggested that NF-kappa B activation by PKR does not require the catalytic activity of the kinase. Here, we provide novel evidence that induction of IKK and NF-kappa B activities proceeds independently of the dsRNA-binding properties of PKR and also verify the kinase-free role of PKR in this process. We also show that the effects of PKR mutants on IKK and NF-kappa B activation are independent of cell transformation but are dependent on the amount of the mutant PKR proteins expressed in cells. These data strongly support an indirect role of PKR in I kappa B alpha phosphorylation by modulating IKK activity through pathways that do not utilize the enzymatic and dsRNA-binding properties of PKR.

3T3 Cells↗

PubMed2001

Identification of a nuclear protein ArpN as a component of human SWI/SNF complex and its selective association with a subset of active genes.

The hSWI/SNF complex remodels the chromatin structure to modulate gene expression. The hSWI/SNF complex is a multiprotein complex with at least 10 different proteins in mammals. In this study, we identified the 45 kDa subunit of the hSWI/SNF complex as ArpN, an actin-related protein. ArpN has a 36% identity and 50% similarity with the human beta-actin, but cannot be classified into any known class of actin-related proteins. ArpN is exclusively localized within the nucleus and appears as the unbound, chromatin-associated, or nuclear matrix associated forms in the nucleus. In the chromatin immunoprecipitation (ChIP) assay, we found the associations of ArpN with the Ets-2 and c-mycP2 promoter regions in HeLa cells. The promoter regions of the hsp70, cyclophilin, beta-globin, TdT, and cd4 genes, however, were not associated with ArpN. The Ets-2 and c-mycP2 genes are expressed actively in HeLa cells, but beta-globin, TdT, and cd4 genes are inactive. The hsp70 and cyclophilin genes have a feature of stress-inducibility. These selective associations of ArpN with a subset of active genes support the proposition that the requirement of hSWI/SNF complex in gene activation is gene specific.

Actins↗

PubMed2001

Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum.

Reactive oxygen species (ROS), such as superoxide anions and hydroxyl radicals, are associated with carcinogenesis and other pathophysiological conditions. Therefore, elimination or inactivation of ROS or inhibition of their excess generation may be beneficial in terms of reducing the risk for cancer and other diseases. Ganoderma lucidum has been used in traditional oriental medicine and has potential antiinflammatory and antioxidant activities. In the present study, we tested the amino-polysaccharide fraction (designated as 'G009') from Ganoderma lucidum for the ability to protect against oxidative damage induced by ROS. G009 significantly inhibited iron-induced lipid peroxidation in rat brain homogenates and showed a dose-dependent inactivation of hydroxyl radicals and superoxide anions. It also reduced strand breakage in phiX174 supercoiled DNA caused by UV-induced photolysis of hydrogen peroxide and attenuated phorbol ester-induced generation of superoxide anions in differentiated human promyelocytic leukaemia (HL-60) cells. These findings suggest that G009 from Ganoderma lucidum possesses chemopreventive potential.

Animals↗

PubMed2001

Promoting sun safety among zoo visitors.

BACKGROUND: Each year, millions of children visit zoological parks, where they are exposed to long bouts of ultraviolet radiation (UVR). We conducted a study in the winter and replicated it in the summer to evaluate an intervention for reducing UVR exposure during the zoo visit. METHODS: Each study used a nonequivalent control group design: one zoological site received the intervention and a second received evaluation only. Key outcome measures consisted of observed prevalence of hat use by exiting children (N = 8,721 and 8,524, respectively, in winter and summer studies) and purchase rates of sunscreen and hats in zoo gift shops. Intervention consisted of tip sheets for parents, children's activities, prompts, and discounts off the price of sunscreen and sun-protective hats. RESULTS: In the summer study, sales of both sunscreen and target hats increased significantly at the intervention site relative to the control site, whereas in the winter study, only sunscreen sales at the intervention site had a significant (relative) increase. Children's hat use increased significantly at the intervention site, but only in the winter study. CONCLUSIONS: The multicomponent program was effective in promoting purchases of sun-safe items, but its impact on children's hat use was inconclusive.

California↗