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Biomedical subjects

S Y Lee

Publications and source records attributed to S Y Lee.

At least 19 recordsLinked to original sources

Effect of beta-alanine administration on carbon tetrachloride-induced acute hepatotoxicity.

Mice were supplemented with beta-alanine (3%) in drinking water for one week. beta-Alanine intake reduced hepatic taurine levels, but elevated cysteine levels significantly. Hepatotoxicity of CCl4 in mice fed with beta-alanine was decreased as determined by changes in serum enzyme activities. Hepatic glutathione and taurine concentrations after CCl4 challenge were increased markedly by beta-alanine intake. The enhanced availability of cysteine for synthesis of glutathione and/or taurine appears to account for the hepatoprotective effects of beta-alanine against CCl4-induced liver injury.

Alanine Transaminase↗

Methods and evaluations of MRI content-adaptive finite element mesh generation for bioelectromagnetic problems.

In studying bioelectromagnetic problems, finite element analysis (FEA) offers several advantages over conventional methods such as the boundary element method. It allows truly volumetric analysis and incorporation of material properties such as anisotropic conductivity. For FEA, mesh generation is the first critical requirement and there exist many different approaches. However, conventional approaches offered by commercial packages and various algorithms do not generate content-adaptive meshes (cMeshes), resulting in numerous nodes and elements in modelling the conducting domain, and thereby increasing computational load and demand. In this work, we present efficient content-adaptive mesh generation schemes for complex biological volumes of MR images. The presented methodology is fully automatic and generates FE meshes that are adaptive to the geometrical contents of MR images, allowing optimal representation of conducting domain for FEA. We have also evaluated the effect of cMeshes on FEA in three dimensions by comparing the forward solutions from various cMesh head models to the solutions from the reference FE head model in which fine and equidistant FEs constitute the model. The results show that there is a significant gain in computation time with minor loss in numerical accuracy. We believe that cMeshes should be useful in the FEA of bioelectromagnetic problems.

Algorithms↗

Fundamental limit of nonscaling fixed-field alternating-gradient accelerators.

Systematic nonlinear space-charge resonances may cause substantial emittance growth in the nonscaling fixed-field alternating-gradient (FFAG) accelerators. To avoid systematic nonlinear space-charge resonances, the phase advance of each nonscaling FFAG cell must avoid pi/2 and pi/3. Using multiparticle numerical simulations, we empirically obtain a minimum tune ramp rate vs the systematic 4th order space-charge resonance strength. We also find that the emittance growth obeys a simple scaling property when the betatron tunes cross the linear half-integer and sum resonances.

Journal Article↗

[11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease.

BACKGROUND: Beta-amyloid (Abeta) plaques are the hallmark of Alzheimer disease (AD). A PET imaging tracer that binds to Abeta plaques in vivo, N-methyl-[(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [(11)C]PIB for "Pittsburgh Compound-B"), has significantly higher binding in subjects diagnosed with dementia of the Alzheimer type (DAT) compared to nondemented controls. The authors used this imaging technique to investigate whether abnormal binding occurs in clinically normal individuals, prior to the development of cognitive changes. METHODS: Forty-one nondemented subjects (age range 20 to 86 years) and 10 patients with DAT (age range 66 to 86 years) underwent [(11)C]PIB PET scanning. Regions of interest were drawn on the MRI over the cerebellar, prefrontal, lateral temporal, occipital, gyrus rectus, precuneus, and striatal cortex. Binding potential values (BPs), proportional to the density of [(11)C]PIB-Abeta binding sites, were calculated using the Logan graphical analysis and the cerebellar cortex for a reference tissue. RESULTS: Patients with DAT had elevated BP values vs nondemented subjects (p < 0.0001). Four of the 41 nondemented subjects had elevated cortical BP values and their BP values as a group were not significantly different from the DAT subjects' BP values. Two of these four nondemented subjects had [(11)C]PIB uptake, both visually and quantitatively, that was indistinguishable from the DAT subjects. CONCLUSIONS: Elevated [(11)C]PIB binding in nondemented subjects suggests that [(11)C]PIB amyloid imaging may be sensitive for detection of a preclinical Alzheimer disease state. Longitudinal studies will be required to determine the association of elevated [(11)C]PIB binding and risk of developing dementia of the Alzheimer type.

Adult↗

AtBAG6, a novel calmodulin-binding protein, induces programmed cell death in yeast and plants.

Calmodulin (CaM) influences many cellular processes by interacting with various proteins. Here, we isolated AtBAG6, an Arabidopsis CaM-binding protein that contains a central BCL-2-associated athanogene (BAG) domain. In yeast and plants, overexpression of AtBAG6 induced cell death phenotypes consistent with programmed cell death (PCD). Recombinant AtBAG6 had higher affinity for CaM in the absence of free Ca2 + than in its presence. An IQ motif (IQXXXRGXXXR, where X denotes any amino-acid) was required for Ca2 +-independent CaM complex formation and single amino-acid changes within this motif abrogated both AtBAG6-activated CaM-binding and cell death in yeast and plants. A 134-amino-acid stretch, encompassing both the IQ motif and BAG domain, was sufficient to induce cell death. Agents generating oxygen radicals, which are known to be involved in plant PCD, specifically induced the AtBAG6 transcript. Collectively, these results suggest that AtBAG6 is a stress-upregulated CaM-binding protein involved in plant PCD.

Amino Acid Motifs↗

New insight of amino acid-based dialysis solutions.

Malnutrition is a major complication of peritoneal dialysis (PD) and is associated with increased morbidity and mortality. Daily losses of proteins and amino acids (AAs) into dialysate contribute to this problem. Previous metabolic balance study demonstrated that treatment with 1.1% AA-based dialysis solution is safe and may improve protein malnutrition in continuous ambulatory peritoneal dialysis (CAPD) patients ingesting low protein intake. Other prospective studies also showed that AA solution can provide nutritional benefit for malnourished PD patients resulting in a significant improvement in some biochemical and/or anthropometric nutritional parameters. However, there are other studies showing no particular improvement in nutritional parameters after long-term use of AA solution. This may be related to the differences in the study design, sample size, methods used to assess nutritional status, and other factors such as dietary intake and comorbidities of study subjects. Published data will be reviewed to further emphasize the nutritional benefit of long-term use of AA solution in malnourished PD patients along with a brief discussion on the various reasons that may partly explain the different study results. We will also present the results of a longitudinal observational study evaluating changes in nutritional parameters following use of one exchange of 1.1% AA solution in malnourished Korean PD patients. A significant improvement of somatic protein status such as lean body mass (LBM) and hand grip strength was observed. No significant change in serum albumin level was noted. Patients with a positive estimated coefficient for LBM in the fitted regression model to the repeated observations over 1 year were classified as responders and patients with neutral or negative coefficient were considered as non-responders. Thirty-one out of 43 malnourished patients (72%) showed nutritional benefit based on the change of LBM. Hand grip strength and back lift strength were significantly higher in responders at baseline. Other baseline parameters did not differ between the two groups.

Amino Acids↗

Different radiological findings with the same pathologic diagnosis due to different age in primary osteosarcoma.

PURPOSE: To examine the imaging characteristics of osteoblastic osteosarcoma in older patients, we compared them with those in adolescents because the radiological features of osteosarcoma can be atypical in elderly patients. MATERIAL AND METHODS: 29 cases of adolescent patients and 12 patients older than 40 years of age were reviewed. All cases were pathologically confirmed as osteoblastic osteosarcoma. The comparative factors were tumor location, plain radiological features including periosteal reactions, and the degree of soft tissue mass with magnetic resonance (MR) imaging. RESULTS: Older patients demonstrated frequent osteolytic findings (83.3%), and none of the tumors showed a significant major periosteal reaction. Seven (58.3%) of the 12 tumors had no soft tissue mass (grade 0) and only three (25%) had a grade 3 mass. The differences in the two groups were statistically significant (P<0.001). CONCLUSION: In older patients, primary osteosarcoma should be considered when making a differential diagnosis of osteolytic lesions without any periosteal reactions and small soft-tissue extensions. In cases with atypical findings, the morphology of specimens (aspiration, core, or surgical biopsy) from the lesion should be recommended when making an accurate diagnosis.

Adolescent↗

Osteogenic potential of cells in vitro derived from haemarthrosis of the knee induced by injury to the anterior cruciate ligament.

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with beta-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH)(2)D(3), a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced. Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury.

Adolescent↗

The local prevalence of COPD by post-bronchodilator GOLD criteria in Korea.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a disease characterised by not fully reversible airflow limitation. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee decided to diagnose COPD using post-bronchodilator spirometry values. We aimed to examine the prevalence and risk factors of COPD in Ansan, an industrialised city of Korea, by using the post-bronchodilator GOLD criteria. We then investigated the implications of brenchodilation on the prevalence of COPD. DESIGN: A total of 3642 participants in the Korean Health and Genome Study were interviewed about age, income, smoking status and respiratory symptoms and completed pulmonary function tests, including postbronchodilator spirometry. RESULTS: COPD prevalence by post-bronchodilator spirometry was 3.7% (134/3642), which was significantly different from that estimated using pre-bronchodilator criteria (7.7%, 282/3642). Exclusion of subjects with significant bronchodilator response (BDR) significantly lowered the prevalence of COPD to 3.3% (117/3572), compared with including subjects with post-bronchodilatory residual obstruction with significant BDR. Prevalence was associated with old age, smoking history, male sex and respiratory symptoms. CONCLUSION: COPD prevalence by post-bronchodilator GOLD criteria was 3.7%, which was much lower than that of pre-bronchodilator criteria. The bronchodilator reversibility test substantially affects estimations of COPD prevalence.

Adult↗

JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila.

Although recent progresses have unveiled the diverse in vivo functions of LKB1, detailed molecular mechanisms governing these processes still remain enigmatic. Here, we showed that Drosophila LKB1 negatively regulates organ growth by caspase-dependent apoptosis, without affecting cell size and cell cycle progression. Through genetic screening for LKB1 modifiers, we discovered the JNK pathway as a novel component of LKB1 signaling; the JNK pathway was activated by LKB1 and mediated the LKB1-dependent apoptosis. Consistently, LKB1-null mutant was defective in embryonic apoptosis and displayed a drastic hyperplasia in the central nervous system; these phenotypes were fully rescued by ectopic JNK activation as well as wild-type LKB1 expression. Furthermore, inhibition of LKB1 resulted in epithelial morphogenesis failure, which was associated with a decrease in JNK activity. Collectively, our studies unprecedentedly elucidate JNK as the downstream mediator of the LKB1-dependent apoptosis, and provide a new paradigm for understanding the diverse LKB1 functions in vivo.

AMP-Activated Protein Kinase Kinases↗

Global physiological understanding and metabolic engineering of microorganisms based on omics studies.

Through metabolic engineering, scientists seek to modify the metabolic pathways of living organisms to facilitate optimized, efficient production of target biomolecules. During the past decade, we have seen notable improvements in biotechnology, many of which have been based on metabolically engineered microorganisms. Recent developments in the fields of functional genomics, transcriptomics, proteomics, and metabolomics have changed metabolic engineering strategies from the local pathway level to the whole system level. This article focuses on recent advances in the field of metabolic engineering, which have been powered by the combined approaches of the various "omics" that allow us to understand the microbial metabolism at a global scale and to develop more effectively redesigned metabolic pathways for the enhanced production of target bioproducts.

Biomedical Engineering↗

Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors.

This study sought to characterize the reduced glutathione (GSH)/oxidized GSSG ratio during osteoclast differentiation and determine whether changes in the intracellular redox status regulate its differentiation through a RANKL-dependent signaling pathway. A progressive decrease of the GSH/GSSG ratio was observed during osteoclast differentiation, and the phenomenon was dependent on a decrease in total glutathione via downregulation of expression of the gamma-glutamylcysteinyl synthetase modifier gene. Glutathione depletion by L-buthionine-(S,R)-sulfoximine (BSO) was found to inhibit osteoclastogenesis by blocking nuclear import of NF-kappaB and AP-1 in RANKL-propagated signaling and bone pit formation by increasing BSO concentrations in mature osteoclasts. Furthermore, intraperitoneal injection of BSO in mice resulted in an increase in bone density and a decrease of the number of osteoclasts in bone. Conversely, glutathione repletion with either N-acetylcysteine or GSH enhanced osteoclastogenesis. These findings indicate that redox status decreases during osteoclast differentiation and that this modification directly regulates RANKL-induced osteoclastogenesis.

Active Transport, Cell Nucleus↗

Awake nasotracheal intubation using fiberoptic bronchoscope in a pediatric patient with Freeman-Sheldon syndrome.

The Freeman-Sheldon syndrome is a congenital disease primarily affecting the facial, limb and respiratory muscles that give rise to classical clinical features including typical whistling face and short webbed neck associated with difficult intubation. We present successful awake nasotracheal intubation in a 6-year-old patient with typical clinical features of Freeman-Sheldon syndrome by using fiberoptic bronchoscope on two separate occasions.

Bronchoscopes↗

Thymidine phosphorylase expression in tumour cells and tumour response to capecitabine plus docetaxel chemotherapy in non-small cell lung cancer.

BACKGROUND: Thymidine phosphorylase (TP) is the key enzyme for capecitabine activation in tumour cells. AIMS: To examine whether TP expression in tumour cells and stroma is predictive of the tumour response to capecitabine plus docetaxel chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Tumour samples were available from 30 of 39 patients enrolled in a previous phase II study of capecitabine/docetaxel chemotherapy in patients with advanced NSCLC. Stromal and tumour cell TP expression was evaluated by immunohistochemistry using monoclonal antibody PD-ECGF. RESULTS: High tumour cell TP expression was found in 13 of 30 cases and was negatively associated with stromal TP expression (p = 0.000). High stromal TP expression was found in 16 of 28 cases and was strongly associated with intense macrophage infiltration (p = 0.002), suggesting that macrophages are the major component of TP expression in the stroma. Tumour response to capecitabine/docetaxel was significantly associated with high tumour cell TP expression (p = 0.004) and low stromal TP expression (p = 0.009). Moreover, high tumour cell TP expression was significantly associated with severe hand-foot syndrome, a toxic side effect of capecitabine (p = 0.01). Improved survival was seen for high tumour cell and low stromal TP expression, although results were not significant (p = 0.6 and 0.3, respectively). CONCLUSIONS: In advanced NSCLC, TP expression in tumour cells and stroma is associated with tumour response to capecitabine/docetaxel chemotherapy, and might be a useful predictor of tumour response to capecitabine based chemotherapy. A large scale prospective study is needed to confirm the prognostic significance of TP expression in NSCLC.

Adult↗

Design of a stability-detecting device for dental implants.

Resonance frequency (RF) analysis technology was used to design a dental implant stability detector. The device uses a miniature-sized electromagnetic triggering rod to elicit vibration in a dental implant. Vibrational signals were recorded via an acoustic receiver. To assess the in vivo performance of the test apparatus, animal models were used. Implants were placed in the left tibia of 12 rabbits using a conventional surgical procedure. Standard 3.2 mm x 8 mm implants were placed in each test tibia with pre-tapping cavities of 3.2 mm and 3.7 mm diameters to simulate either a 'well-fitting' or a 'loosely fitting' situation. The RF values of the test implants were detected by the newly developed device which was directly mounted on the healing abutments of the implants. The results showed that the RF values of the implants under well-fitting conditions significantly increased (p < 0.01) 3 weeks after surgery and reached a plateau at around 6-7 weeks. Meanwhile implants with higher initial RF values had shorter healing times and higher final RF values at the plateau. Based on these findings, it was concluded that the idea of using the current designed device for detecting the degree of bone healing during the osseointegration process seems feasible.

Animals↗

Angiopoietin-1 reduces iopromide-induced endothelial cell apoptosis through activation of phosphatidylinositol 3'-kinase/p70 S6 kinase.

Radiocontrast media can induce vascular endothelial cell apoptosis. Apoptotic damage to the vascular endothelium is an important mechanism in vascular disease. Several growth factors with anti-apoptotic effects may help protect the vascular endothelium from apoptosis. The present study evaluated whether the radiocontrast agent iopromide induces apoptosis in human umbilical vein endothelial cells and also whether angiopoietin-1 (Ang1) protects against iopromide-induced apoptosis through the p70 S6 kinase-dependent signaling pathway. Iopromide induced apoptosis in vascular endothelial cells in a dose-dependent manner. Ang1 reduced iopromide-induced apoptosis in a dose-dependent manner. Wortmannin and LY294002, phosphatidylinositol 3'-kinase inhibitors, decreased the Ang1-induced anti-apoptotic effect. Ang1 mediates the activation of mTOR/ribosomal protein p70 S6 kinase through phosphatidylinositol-3' kinase. Wortmannin and rapamycin, an inhibitor of mTOR, suppressed Ang1-induced p70 S6 kinase phosphorylation and partially inhibited the Ang1-induced anti-apoptotic effect. These results suggest that Ang1 may protect vascular endothelial cells from iopromide-induced apoptosis through phosphatidylinositol 3'-kinase and mTOR/S6 kinase. Pretreatment with Ang1 could help maintain normal vascular endothelial cell integrity before and during systemic radiocontrast administration.

Analysis of Variance↗

Modified cellular automaton model for the prediction of dendritic growth with melt convection.

A modified cellular automaton (MCA) coupled with a momentum and species transport model has been developed in order to predict the evolution of dendritic morphology during solidification of alloys in the presence of melt convection. In the present model, the cellular automaton algorithm for dendritic growth is incorporated with the transport model, for calculating fluid flow and mass transfer by both convention and diffusion. The MCA model takes into account the effects of the constitutional undercooling and the curvature undercooling on the equilibrium interface temperature. It also considers the preferred growth orientation of crystals and solute redistribution during solidification. In the transport model, which is coupled with cellular automaton approach, the SIMPLE scheme is employed to solve the governing equations of momentum and species transfers. The present model was applied to model solutal dendritic growth of an Al-3mass%Cu alloy in a forced flow. The simulations reproduced the typical asymmetric growth features of convective dendrites with various preferred orientations. The effects of inlet flow velocity on the solute redistribution and the growth velocity of a dendritic tip were quantitatively investigated.

Journal Article↗