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H M Kwon

Publications and source records attributed to H M Kwon.

At least 19 recordsLinked to original sources
PubMed2006

Large discrepancies in cellular distribution of the tonicity-induced expression of osmoprotective genes and their regulatory transcription factor TonEBP in rat brain.

Osmoprotective genes are tonicity-activated genes involved in cellular osmoadaptation to hypertonicity and considered to be regulated by a specific transcription factor called tonicity-responsive enhancer-binding protein (TonEBP). In the brain we had previously established that TonEBP was expressed and tonicity-induced in neurons only. Here we have compared in various brain regions of rats subjected to systemic hypertonicity, the cellular expression of TonEBP through immunocytochemistry and the cellular expression of osmoprotective genes, namely aldose reductase (AR), sodium-dependent myo-inositol transporter (SMIT), betaine/GABA transporter (BGT1) and taurine transporter (TauT), by in situ hybridization using non-radioactive digoxigenin-labeled riboprobes. In neurons where TonEBP was strongly tonicity-induced, AR-mRNA labeling was strongly increased in some subsets (e.g. hippocampus pyramidal cells, cerebellar Purkinje cells and neurons of the hypothalamic magnocellular nuclei) but remained undetectable in some other subsets (e.g. neurons in cerebral cortex). Tonicity-induced AR-mRNA labeling was observed only several hours after the tonicity-induced expression of TonEBP. SMIT-mRNA labeling was tonicity-induced as densely and evenly distributed dots in neuron poor regions (e.g. cerebral cortex layer I and hippocampus stratum lacunosum-moleculare). The tonicity-induced expression of SMIT-mRNA may thus occur in non-neuronal cells, presumably astrocytes, where TonEBP is neither significantly expressed, nor tonicity-induced. In neurons showing a strong tonicity-induced expression of TonEBP, no SMIT-mRNA labeling was observed. BGT1-mRNA and TauT-mRNA labeling could not be detected, even after systemic hypertonicity. The present work reveals large discrepancies between the cellular distribution of the tonicity-induced expression of osmoprotective genes and that of their regulatory transactivator TonEBP. Depending on the cell subsets and the osmoprotective genes, TonEBP may appear insufficient or conversely unnecessary for the tonicity-induced activation of an osmoprotective gene. Altogether our results show that brain cells, even from the same class, activate distinct osmoprotective genes through distinct activation processes to adapt to hypertonicity.

Aldehyde Reductase↗
PubMed2005

Differential cellular distribution of tonicity-induced expression of transcription factor TonEBP in the rat brain following prolonged systemic hypertonicity.

In a previous work performed on cerebral cortex and hippocampus we reported that tonicity-responsive enhancer binding protein (TonEBP), originally identified as a transactivator of osmoprotective genes involved in osmoadaptation of renal cells, was induced in neurons only, but to varying levels, following acute systemic hypertonicity. Whether or not this cellular specificity reflected a unique ability of neurons or a differential time course among brain cells for tonicity-induction of TonEBP was investigated throughout the brain in this study by subjecting the animals to prolonged systemic hypertonicity. In normal rats, TonEBP immunolabeling and TonEBP-mRNA in situ hybridization labeling showed a widespread, uneven and parallel distribution. TonEBP was expressed primarily in the cell nuclei of neurons, where it was heterogeneously distributed in a nucleoplasmic and a granular pool. In rats subjected to prolonged systemic hypertonicity, TonEBP labeling increased in the cell nuclei of neurons only. The tonicity-induced expression of TonEBP for a given cell group of neurons was rather uniform but varied greatly among neuronal cell groups and was positively correlated with the average size of the cell nuclei, as determined by quantitative analysis of digitized images. The detailed distribution of tonicity-induced expression of TonEBP is reported throughout the brain. In normal rats, a very minor proportion of non-neuronal cells, identified as a subset of astrocytes and possibly oligodendrocytes, showed faint nuclear immunolabeling, which however did not increase in hypertonic animals. Ependymocytes, capillary endothelial cells, and microglial cells showed no TonEBP labeling, even in hypertonic animals. Altogether our data indicate that neurons, albeit possibly to a varying extent, are the only brain cells able to use TonEBP-mediated processes for adaptation to a systemic hyperosmotic unbalance.

Animals↗
PubMed2004

Transcription factor tonicity-responsive enhancer-binding protein (TonEBP) which transactivates osmoprotective genes is expressed and upregulated following acute systemic hypertonicity in neurons in brain.

Tonicity-responsive enhancer-binding protein (TonEBP) was initially identified as a transcription factor involved in adaptation of renal cells to hypertonicity by activation of osmoprotective genes encoding proteins for accumulation of compatible osmolytes. Since brain osmoadaptation is observed in relationship to neurological disorders resulting from pathological osmotic disbalances of blood plasma we have investigated through immunocytochemistry TonEBP expression in cerebral cortex and hippocampus of normal rat and rats submitted to an acute systemic hypertonicity or to a prolonged systemic hypotonicity. TonEBP-expressing cells were identified using double immunofluorescence and appropriate cell type markers. Their relative proportion was determined by quantitative image analysis. In normal rats TonEBP expressed primarily in neurons where it was strictly located in the cell nucleus but heterogeneously distributed into a nucleoplasmic pool and a granular pool. In animals made acutely hypertonic TonEBP labeling increased dramatically exclusively in the nuclei of neurons and reached a maximum within 1 h. In hypertonic animals TonEBP labeling covered the whole cell nucleus of virtually all neurons, appeared finely punctuated but was no more granular. Optical density of the labeling as determined by image analysis correlated linearly with the increased plasma osmolality. In animals made hypotonic for several days no conspicuous decrease of TonEBP labeling was observed. In normal animals a very minor proportion of non-neuronal cells showed a faint TonEBP nuclear labeling. This proportion increased slightly in hypertonic animals. Nevertheless these non-neuronal TonEBP-positive nuclei which belonged to oligodendrocytes and to a small subpopulation of astrocytes remained always very weakly labeled when compared with neuron nuclei. Brain capillary endothelial cells as well as microglial cells showed no TonEBP-labeling even in hypertonic animals. Our data demonstrate that in brain TonEBP is significantly expressed and tonicity-overexpressed in neurons and accordingly suggest that neurons only among brain cells accumulate compatible osmolytes through TonEBP-mediated activation of osmoprotective genes to adapt to acute systemic hypertonicity.

Animals↗
PubMed2003

S1 glycoprotein gene analysis of infectious bronchitis viruses isolated in Korea.

Fifteen isolates of Infectious bronchitis virus (IBV) were obtained from the kidney, trachea, and cecal tonsil of IB suspected chickens between 2001 and 2002 years in Korea. The S1 glycoprotein gene of IBV isolates were amplified by reverse transcriptase - polymerase chain reaction (RT-PCR) and analyzed by restriction fragment length polymorphism (RFLP) analysis. Fifteen Korean IBV isolates were classified into 4 groups by their RFLP patterns using restriction enzymes, HaeIII, BstYI, and XcmI. The RFLP patterns for 3, 1, and 1 of 15 isolates corresponded to the patterns of IBV Arkansas, Connecticut, and Massachusetts strains, respectively. Ten of 15 isolates generated unique KM91 RFLP pattern that was observed in the IBV KM 91 strain previously isolated in Korea. To confirm genetic diversity in the S1 genes of IBV isolates, viral RNAs of representative 9 of 15 IBV isolates were amplified, cloned, sequenced and compared with published sequences for non-Korean IBV strains. Korean IBV isolates showed amino acid sequence similarity between 61.8% (K446-01 and K161-02) and 96.1% (K281-01 and K210-02) with each other and they showed amino acid sequence similarity between 42.9% (K161-02 and GA980470) and 96.5% (K203-02 and KB8523) compared to non-Korean IBV strains. By phylogenetic tree analysis, Korean IBV field isolates were branched into five clusters in which 3 clusters were differentiated from non-Korean IBV strains. Especially, Korean IBV isolates K069-01, K507-01, K774-01 and K142-02 formed a separate cluster. It seems that IBVs continue to evolve and IBVs showing various genetic differences may cocirculate in Korea.

Amino Acid Sequence↗
PubMed2001

Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro.

Leptin, the product of ob gene, is an endocrine hormone that regulates adipose tissue mass. Recently, leptin has been found to generate a growth signal involving a tyrosine kinase-dependent intracellular pathway and promote angiogenic processes via activation of leptin receptor (Ob-R) in endothelial cells. However, it is not clear how leptin functions to promote multi-step processes involved in the neovascularization at the atherosclerotic plaque. We have examined the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and Ob-R in human atherosclerotic lesions, leptin-mediated angiogenesis in vivo and in vitro. Immunohistochemical analysis of human atherosclerotic aorta revealed an increased expression of Ob-R in the intima of neorevascularized regions and of both MMPs and TIMPs predominantly in the endothelial lining of intimal neovessels and macrophages/foam cells. In the rat corneal angiogenesis assay, leptin elicited a comparable sensitivity of angiogenic activity to those of vascular endothelial growth factor (VEGF). The immunohistological analysis of the leptin-treated rat cornea showed definitive rises in Ob-R, MMPs and TIMPs expression as well as those of VEGF receptor (VEGFR-1). Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) and elevation of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression in a dose-dependent manner. Leptin also induced increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery smooth muscle cells (HCASMCs). These findings suggest that leptin, a hormone with pluralistic properties including a mitogenic activity on vascular endothelial cells, plays a role in matrix remodeling by regulating the expression of MMPs and TIMPs. Taken together, our findings further provide evidences for leptin's role as an angiogenesis inducer in the normal organ (rat cornea) and in aberrant vasculature under duress like atherosclerosis.

Animals↗
PubMed2001

Line quadrisection errors in normal subjects.

Many studies have investigated line bisection behaviors in normal individuals and patients with hemispatial neglect. However, little is known about what happens when subjects attempt to fractionate line into more than two equal components (e.g., line quadrisection). Thirty right handed normal subjects were asked to place a mark either 25% (left quadrisection) or 75% (right quadrisection) of the distance along on a 240 mm line. On average, they placed the left quadrisection mark significantly to the left (- 4.2+/-6.7 mm) from the true quadrisection point but they were relatively accurate on the right quadrisection task (1.0+/-6.7 mm). However, comparison of actual quadrisection performances with those of expected performance based on subjective midpoint disclosed that both right and left quadrisection marks deviate toward each end of the line. Individual data analysis also support this trend because majority of subjects showed the lateral deviation in either or both quadrisection tasks. Therefore, in the left quadrisection task the pseudoneglect (leftward bias) in bisection and the lateral bias are additive, resulting in a robust left lateral deviation, whereas in the right quadrisection, these two biases nullify each other, resulting in accurate performance.

Adolescent↗
PubMed2001

Elective endovascular treatment of descending thoracic aortic aneurysms and chronic dissections with stent-grafts.

PURPOSE: To report our experience of endovascular stent-graft placement in patients with descending thoracic aortic dissections and aneurysms and to evaluate the feasibility, safety, and clinical outcomes of the treatment. MATERIALS AND METHODS: Stent-grafts were placed in the descending thoracic aortas of 23 patients with saccular aneurysms (n = 11) and Stanford type B chronic aortic dissections of the descending thoracic and abdominal aorta (n = 12). All stent-grafts were individually constructed of self-expandable stainless steel stents covered with polytetrafluoroethylene. Vascular access was achieved through the femoral artery in all patients. Clinical status of each patient was monitored and postoperative CT was performed within 1 month of the procedure and at 3-12-month intervals after the procedures. RESULTS: Successful exclusion of the primary entry tears of dissections and the inlets of saccular aneurysms was achieved in all but two patients with aortic dissection. The overall technical success rate was 91.3% (dissection: 10 of 12 = 83%; aneurysm: 11 of 11 = 100%). All patients in whom technical success was achieved showed complete thrombosis and significant decrease in diameter of the thoracic false lumen (preoperative: 5.3 cm +/- 0.9; postoperative: 4.3 cm +/- 0.9; P = .004) or aneurysm sac (preoperative: 5.3 cm +/- 1.7; postoperative: 2.8 cm +/- 2.5; P = .001). In addition, five patients demonstrated complete resolution of the dissected thoracic false lumen (n = 2) and aneurysm sac (n = 3). However, in all patients with aortic dissection, the abdominal aorta was not significantly changed in size (P = .302) and shape and their false lumen flows remained persistent. Immediate postoperative complications were detected in 12 patients (52%); 10 had fever, leukocytosis, and elevation of C-reactive protein, another had wound infection, and another had transient abdominal pain. Three patients died 2, 3, and 12 months after the procedure: one from septic shock, another from underlying mediastinitis, and the other from an unexplained cause. The remaining 20 patients were well after the procedure (1-9 days; mean, 3 days), without any stent-graft-related complications or discomfort (follow up period: 10-65 mo; mean: 25.1 mo +/- 15.6). The cumulative survival rate after the stent graft was 100% at 30 days and 91% at 12 months. CONCLUSIONS: For treatment of aortic dissection and saccular aneurysm of the descending thoracic aorta, endovascular stent-graft repair may be a technically feasible and effective treatment modality.

Adult↗
PubMed2001

Transcriptional regulation by changes in tonicity.

Most organisms respond to a hypertonic environment by accumulating small organic solutes. In contrast to high concentrations of electrolytes, the small organic solutes do not perturb the activity of enzymes and other macromolecules within the cell. When the renal medulla becomes hypertonic during antidiuresis, multiple signaling pathways are activated. Here, we review the role of tonicity responsive enhancers (TonE) binding protein (TonEBP), a transcription factor activated in hypertonic cells. The activation of TonEBP by hypertonicity results from its translocation to the nucleus as well as an increase in TonEBP mRNA and protein. TonEBP may have a role beyond the response to tonicity since it is highly expressed in activated lymphocytes and in developing tissues.

Animals↗
PubMed2001

A case of cutaneous bronchogenic cyst over the left scapula.

Bronchogenic cyst is noted shortly after birth or in early childhood and usually presents as a swelling or draining sinus in the presternal area. Its origin and pathogenesis can be explained as a developmental anomaly of the tracheobronchial buds from the primitive foregut. The patient was a 4-year-old boy with a child-fist-sized soft mass over his left scapula, which had been detected at birth and had been gradually growing. Grossly, it appeared to be a simple cyst with clear mucoid fluid. Histopathological study demonstrated a unilocular cyst composed of ciliated pseudostratified columnar epithelia, interspersed goblet cells, smooth muscles, and mucous glands on the cyst wall, which are features compatible with cutaneous bronchogenic cyst.

Bronchogenic Cyst↗
PubMed2001

Hypertonicity-induced phosphorylation and nuclear localization of the transcription factor TonEBP.

The accumulation of compatible osmolytes during osmotic stress is observed in virtually all organisms. In mammals, the hypertonicity-induced expression of osmolyte transporters and synthetic enzymes is conferred by the presence of upstream tonicity-responsive enhancer (TonE) sequences. Recently, we described the cloning and initial characterization of TonE-binding protein (TonEBP), a transcription factor that translocates to the nucleus and associates with TonE sequences in a tonicity-dependent manner. We now report that hypertonicity induces an increase in TonEBP phosphorylation that temporally correlates with increased nuclear localization of the molecule. TonEBP phosphorylation is not affected by a number of kinase inhibitors, including the p38 inhibitor SB-203580. In addition, in vitro binding assays show that the association of TonEBP with TonE sequences is not affected by phosphorylation. Thus TonEBP phosphorylation is an early step in the response of cells to hypertonicity and may be required for nuclear import or retention.

Animals↗
PubMed2001

Amino acid depletion activates TonEBP and sodium-coupled inositol transport.

The expression of the osmosensitive sodium/myo-inositol cotransporter (SMIT) is regulated by multiple tonicity-responsive enhancers (TonEs) in the 5'-flanking region of the gene. In response to hypertonicity, the nuclear abundance of the transcription factor TonE-binding protein (TonEBP) is increased, and the transcription of the SMIT gene is induced. Transport system A for neutral amino acids, another osmosensitive mechanism, is progressively stimulated if amino acid substrates are not present in the extracellular compartment. Under this condition, as in hypertonicity, cells shrink and mitogen-activated protein kinases are activated. We demonstrate here that a clear-cut nuclear redistribution of TonEBP, followed by SMIT expression increase and inositol transport activation, is observed after incubation of cultured human fibroblasts in Earle's balanced salts (EBSS), an isotonic, amino acid-free saline. EBSS-induced SMIT stimulation is prevented by substrates of system A, although these compounds do not compete with inositol for transport through SMIT. We conclude that the incubation in isotonic, amino acid-free saline triggers an osmotic stimulus and elicits TonEBP-dependent responses like hypertonic treatment.

Adolescent↗
PubMed2001

Cell and molecular biology of organic osmolyte accumulation in hypertonic renal cells.

When the renal medulla becomes hypertonic in association with the formation of concentrated urine, the cells of the medulla avoid the stress of high intracellular salts by accumulating small non-perturbing organic osmolytes. The response has been studied in most detail in cultured kidney-derived cells, and confirmed in studies of the intact kidney. The non-perturbing osmolytes, myo-inositol, betaine, and sorbitol, are accumulated because of stimulation of the transcription of the genes for the proteins that catalyze their accumulation by transport or synthesis. The genes involved have all been cloned and sequenced and contain tonicity responsive regulatory elements (TonEs) in their 5' region. During hypertonicity, the elements are occupied by TonE-binding protein, a transacting factor that has been cloned and characterized. Current efforts focus on identifying the mechanism by which cells sense hypertonicity and how that leads to activation of TonE-binding protein.

Animals↗
PubMed2001

Hemodynamic effects on atherosclerosis-prone coronary artery: wall shear stress/rate distribution and impedance phase angle in coronary and aortic circulation.

The objective of the present study was to evaluate the hemodynamic characteristics of an atherosclerosis-prone coronary artery compared to the aorta. We describe three- dimensional spatial patterns of wall shear stress (WSS) according to the impedance phase angle in pulsatile coronary and aorta models using in vivo hemodynamic parameters and computed numerical simulations both qualitatively and quantitatively. Angiography of coronary arteries and aortas were done to obtain a standard model of vascular geometry. Simultaneously to the physiologic studies, flow-velocity and pressure profiles from in vivo data of the intravascular Doppler and pressure wire studies allowed us to include in vitro numerical simulations. Hemodynamic variables, such as flow-velocity, pressure and WSS in the coronary and aorta models were calculated taking into account the effects of vessel compliance and phase angle between pressure and flow waveforms. We found that there were spatial fluctuations of WSS and in the recirculation areas at the curved outer wall surface of the coronary artery. The mean WSS of the calculated negative phase angle increased in the coronary artery model over that in the aorta model and the phase angle effect was most prominent on the calculated amplitude of WSS of the coronary artery. This study suggests that the rheologic property of coronary circulation, such as the fluctuation of WSS/WSR induces several hemodynamic characteristics. A separation of flow-velocity, a difference in phase between pressure conductance and blood flow and prominent temporal and/or spatial oscillatory fluctuations of the shear forces as a function of pulsatile flow might be important factors in atherogenesis and progression of atherosclerosis.

Adult↗
PubMed2001

Total occlusion of left main coronary artery by dilated main pulmonary artery in a patient with severe pulmonary hypertension.

A 34-year-old woman was admitted to the hospital because of recently aggravated right heart failure without angina for 5 months. When she was 25 years old, patch repair with Polytetrafluoroethylene (PTFE) was performed for the secondum type of atrial septal defect (ASD) with moderate pulmonary hypertension. The chest PA, echocardiography and cardiac catheterization at current admission revealed Eisenmenger syndrome without intracardiac shunt. Chest CT scan with contrast revealed markedly dilated pulmonary trunk, both pulmonary arteries and concave disfigurement of the left side of the ascending aorta suggesting extrinsic compression, as well as total occlusion of the ostium of the left main coronary artery that was retrogradly filled with collateral circulation from the right coronary artery. The coronary angiography showed normal right coronary artery and the collaterals that come out from the conus branch to the mid-left anterior descending artery (LAD) and that from distal right coronary artery to the left circumflex artery (LCX) and to the distal LAD, respectively. On aortography, the left main coronary artery was not visualized with no stump, suggestive of total occlusion of the ostium of the left main coronary artery. From our experience, it is possible to say that the occlusion of the ostium of the left main coronary can be induced by the dilated pulmonary artery trunk due to ASD with pulmonary hypertension and that, if the ASD closure was too late, the narrowing or obstruction of the left coronary artery could not be resolved even after operation owing to irreversible pulmonary hypertension.

Adult↗
PubMed2000

Nuclear redistribution of tonicity-responsive enhancer binding protein requires proteasome activity.

Tonicity-responsive enhancer binding protein (TonEBP) is the transcription factor that regulates tonicity-responsive expression of the genes for the sodium-myo-inositol cotransporter (SMIT) and the sodium-chloride-betaine cotransporter (BGT1). Hypertonicity stimulates the activity of TonEBP due to a combination of increased protein abundance and increased nuclear distribution (proportion of TonEBP that is in the nucleus). We found that inhibitors of proteasome activity markedly reduce the induction of SMIT and BGT1 mRNA in response to hypertonicity. These inhibitors also reduce hypertonicity-induced stimulation of expression of a reporter gene controlled by the tonicity-responsive enhancer. Western and immunohistochemical analyses revealed that the proteasome inhibitors reduce the hypertonicity-induced increase of TonEBP in the nucleus by inhibiting its nuclear redistribution without affecting its abundance. Although the nuclear distribution of TonEBP is sensitive to inhibition of proteasome activity as is that of nuclear factor (NF)-kappaB, the signaling pathways appear to be different in that hypertonicity does not affect the nuclear distribution of NF-kappaB. Conversely, treatment with tumor necrosis factor-alpha increases the nuclear distribution of NF-kappaB but not TonEBP.

Animals↗
PubMed2000

Bidirectional regulation of tonicity-responsive enhancer binding protein in response to changes in tonicity.

Tonicity-responsive enhancer binding protein (TonEBP) regulates transcription of tonicity responsive genes such as the sodium-myo-inositol cotransporter (SMIT), the sodium-chloride-betaine cotransporter (BGT1), and aldose reductase (AR). To characterize signals that activate TonEBP in Madin-Darby canine kidney (MDCK) cells, the abundance and nuclear distribution of TonEBP were studied after the osmolality of the culture medium was changed. Hypertonicity but not hyperosmolality is effective in activation of TonEBP as expected. Surprisingly, exposure to hypotonic medium leads to a dramatic downregulation of TonEBP both in abundance and nuclear distribution, indicating that under isotonic conditions, TonEBP is at a low-level activated state and can respond to both increase and decrease in tonicity. Additional experiments suggest that cellular ionic strength is the signal that initiates regulation of TonEBP. The increase in abundance of TonEBP is mediated by an increase in mRNA abundance and a parallel increase in synthesis of TonEBP. The stability of TonEBP mRNA is not affected by hypertonicity indicating that transcription plays a major role in the induction of TonEBP by hypertonicity.

Animals↗
PubMed2000

Expression of osteopontin in calcified coronary atherosclerotic plaques.

Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.

Aged↗