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Biomedical subjects

Jong-Min Lee

Publications and source records attributed to Jong-Min Lee.

8 recordsLinked to original sources

NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons.

NF-E2-related factor-2 (Nrf2) regulates the gene expression of phase II detoxification enzymes and antioxidant proteins through an enhancer sequence referred to as the antioxidant-responsive element (ARE). In this study, we demonstrate that Nrf2 protects neurons in mixed primary neuronal cultures containing both astrocytes ( approximately 10%) and neurons ( approximately 90%) through coordinate up-regulation of ARE-driven genes. Nrf2-/- neurons in this mixed culture system were more sensitive to mitochondrial toxin (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine or rotenone)-induced apoptosis compared with Nrf2+/+ neurons. To understand the underlying mechanism of this observed differential sensitivity, we compared the gene expression profiles using oligonucleotide microarrays. Microarray data showed that Nrf2+/+neuronal cultures had higher expression levels of genes encoding detoxification enzymes, antioxidant proteins, calcium homeostasis proteins, growth factors, neuron-specific proteins, and signaling molecules compared with Nrf2-/- neuronal cultures. As predicted from the microarray data, Nrf2-/- neurons were indeed more vulnerable to the cytotoxic effects of ionomycin- and 2,5-di-(t-butyl)-1,4-hydroquinone-induced increases in intracellular calcium. Finally, adenoviral vector-mediated overexpression of Nrf2 recovered ARE-driven gene expression in Nrf2-/- neuronal cultures and rescued Nrf2-/- neurons from rotenone- or ionomycin-induced cell death. Taken together, these findings suggest that Nrf2 plays an important role in protecting neurons from toxic insult.

1-Methyl-4-phenylpyridinium↗

Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis.

The antioxidant responsive element (ARE) mediates transcriptional regulation of phase II detoxification enzymes and antioxidant proteins such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases, and glutamate-cysteine ligase. In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes and identify Nrf2-dependent genes by oligonucleotide microarray analysis using primary cortical astrocytes from Nrf2(+/+) and Nrf2(-/-) mice. Nrf2(-/-) astrocytes had decreased basal NQO1 activity and no induction by tert-butylhydroquinone compared with Nrf2(+/+) astrocytes. Similarly, both basal and induced levels of human NQO1-ARE-luciferase expression in Nrf2(-/-) astrocytes were significantly lower than in Nrf2(+/+) astrocytes. Furthermore, human NQO1-ARE-luciferase expression in Nrf2(-/-) astrocytes was restored by overexpression of Nrf2, whereas ARE activation in Nrf2(+/+) astrocytes was completely blocked by dominant-negative Nrf2. In addition, we observed that Nrf2-dependent genes protected primary astrocytes from H(2)O(2)- or platelet-activating factor-induced apoptosis. In support of these observations, we identified Nrf2-dependent genes encoding detoxification enzymes, glutathione-related proteins, antioxidant proteins, NADPH-producing enzymes, and anti-inflammatory genes using oligonucleotide microarrays. Proteins within these functional categories are vital to the maintenance and responsiveness of a cell defense system, suggesting that an orchestrated change in gene expression via Nrf2 and the ARE gives a synergistic protective effect against oxidative stress.

Animals↗

Evaluation of automated and semi-automated skull-stripping algorithms using similarity index and segmentation error.

The skull-stripping in the MR brain image appears to be a key issue in neuroimage analysis. In this paper, we evaluated the accuracy and efficiency of both automated and semi-automated skull-stripping methods. The evaluation was performed on both simulated and real data with the ground truth in skull-stripping. Although automated method showed better efficient results, it should require additional intervention. In contrast to that, semi-automated method showed better accurate results, but it was time consuming and prone to operator bias. Therefore, it might be practical that the semi-automated method was used as the post-processing of the automated one.

Algorithms↗

A PC-based high-quality and interactive virtual endoscopy navigating system using 3D texture based volume rendering.

As an alternative method to optical endoscopy, visual quality and interactivity are crucial for virtual endoscopy. One solution is to use the 3D texture map based volume rendering method that offers high rendering speed without reducing visual quality. However, it is difficult to apply the method to virtual endoscopy. First, 3D texture mapping requires a high-end graphic workstation. Second, texture memory limits reduce the frame-rate. Third, lack of shading reduces visual quality significantly. As 3D texture mapping has become available on personal computers recently, we developed an interactive navigation system using 3D texture mapping on a personal computer. We divided the volume data into small cubes and tested whether the cubes had meaningful data. Only the cubes that passed the test were loaded into the texture memory and rendered. With the amount of data to be rendered minimized, rendering speed increased remarkably. We also improved visual quality by implementing full Phong shading based on the iso-surface shading method without sacrificing interactivity. With the developed navigation system, 256 x 256 x 256 sized brain MRA data was interactively explored with good image quality.

Anatomy, Cross-Sectional↗

Modified magnetic resonance image based parcellation method for cerebral cortex using successive fuzzy clustering and boundary detection.

Development of the accurate and reproducible parcellation of the human brain can be used to resolve the complex structure-functional relationships in the brain. We propose a modified parcellation method that provides the reliable and reproducible regions of interest using successive fuzzy c-means (sFCM) and boundary-detection algorithm. This method displays simultaneously both original brain image for identifying the sulcal landmarks and its tissue-classified image for referring to patterns of sulci. The whole cerebral region is extracted by the semiautomated region growing method and then classified to gray matter, white matter, and cerebrospinal fluid by sFCM. Referred to the other previous researches, the volume ratio of gray matter to white matter was shown to find that the efficiency of classification was improved (conventional FCM: 0.80 +/- 0.12 vs. sFCM: 1.57 +/- 0.18). Inter-rater reliability, estimated by the regression analysis, demonstrated that the proposed method was more reliable and reproducible than conventional methods [ANALYZE: correlation coefficient (CC)=0.341, Sig.=0.335 vs. proposed method: CC=0.816, Sig.=0.004]. The volume ratio of the whole cerebrum to the parceled object can be used to investigate structural abnormalities for the pathological detection of the various mental diseases such as schizophrenia, obsessive-compulsive disorder.

Algorithms↗

Intensity based affine registration including feature similarity for spatial normalization.

This paper presents a new spatial normalization with affine transformation. The quantitative comparison of brain architecture across different subjects requires a common coordinate system. For the analysis of a specific brain area, it is required to normalize and compare a region of interest and global brain. Intensity based registration method matches the global brain well. But a region of interest may not be locally normalized compared to feature based method. The method of this paper uses feature similarities of local region as well as intensity similarities. The lateral ventricle and the central gray nuclei of brain including the corpus callosum, which is used for features in Schizophrenia detection, is appropriately normalized. In the results section, our method reduces the difference of feature area such as corpus callosum (7.7%, 2.4%) and lateral ventricle (8.2%, 13.5%) compared with mutual information and Talairach methods.

Algorithms↗

Microarray analysis reveals an antioxidant responsive element-driven gene set involved in conferring protection from an oxidative stress-induced apoptosis in IMR-32 cells.

The present study was designed to investigate how tert-butylhydroquinone (tBHQ) prevents hydrogen peroxide-induced apoptosis in IMR-32 cells. tBHQ pretreatment (10 microm) attenuated hydrogen peroxide-induced cell death and reduced the number of TUNEL (terminal deoxynucleotidyltransferase-mediated, dUTP-incorporated nick end labeling)-positive cells. We hypothesize that tBHQ-mediated activation of the antioxidant responsive element is critical for generating this protective response. Addition of LY294002, a selective inhibitor of phosphatidylinositol 3-kinase (PI3K), 30 min prior to tBHQ treatment completely reversed the protective effect of tBHQ. Oligonucleotide microarrays were used to analyze the gene expression profile associated with tBHQ treatment in the absence and presence of LY294002. Ranking analysis using Affymetrix's difference call indicated that the expression of 137 genes changed with tBHQ treatment. Further analysis using the coefficient of variation for -fold change or average difference change reduced the list to 63 increased and 0 decreased genes. Reverse transcription-PCR for selected genes also confirmed the gene expression pattern. Many of these genes function to combat oxidative stress and increase the detoxification potential of the cells. Inhibition of PI3K significantly blocked the enhanced expression of 49 of the 63 genes induced by tBHQ. These data are the first to show a set of programmed cell life genes involved in conferring protection from an oxidative stress-induced apoptosis.

Antioxidants↗

Agrobacterium-mediated transformation of herbicide resistance in creeping bentgrass and colonial bentgrass.

Embryogenic calli were induced from the seeds of creeping bentgrass (Agrostis palustris Huds.) cv. Regent and colonial bentgrass (Agrostis Tenuis Sibth. Fl. Oxen.) cv. Tiger. The embryogenic calli were precultured on fresh medium for 4-7 days and then co-cultivated with Agrobacterium tumefaciens, LBA4404, which contains plasmid vector-pSBGM harboring bar coding region, synthetic green fluorescent protein (sGFP) coding region and matrix attachment region (MAR). After 3 days of co-cultivation, the calli were washed thoroughly and transferred to MS medium containing 2 mg/L of 2, 4-D, 12-15 mg/L phosphinothricin (PPT) and 250 mg/L of cefotaxime. After 2-3 months of selection, the actively growing calli of 'Regent' and 'Tiger' were transferred to MS medium with 12-15 mg/L PPT and 250 mg/L cefotaxime for regeneration. The putative transformants were maintained on MS medium with 3 mg/L PPT for long period but control died within 1 month. After establishing in greenhouse, the transformants also showed strong resistance to 0.4% of herbicide Basta but control plants died within 2 weeks. Under confocal microscope, both young leaves and roots showed significant GFP expression. PCR analysis revealed the presence of a DNA fragment of GFP gene at the expected size (380 bp) in the transformants and its absence in a randomly selected control plant.

Agrostis↗