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Biomedical subjects

H J Kwon

Publications and source records attributed to H J Kwon.

At least 19 recordsLinked to original sources

Methanolic extract of Pterocarpus santalinus induces apoptosis in HeLa cells.

Ptercarpus santalinus (Fabaceae) has been used as a folk remedy in Korea, and it has been shown to exhibit antiinflammations, antiulcers and anticancer effects. In this study, therefore, we report the cytotoxic activity and the mechanism of cell death exhibited by the methanol extract of Ptercarpus santalinus (MEPS) against human cervical adenocarcinoma cell line, HeLa. Treatment of HeLa cells with various concentrations of MEPS resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as determined by cell viability, chromatin condensation, DNA fragmentation and sub-G1 phase accumulation. In Western blot analysis, apoptosis in the HeLa cells was associated with the release of cytochrome C from mitochondria into the cytosol, activation of caspases-3, -8, -9 and proteolytic cleavage of PARP. These results suggest that MEPS exhibits antiproliferative effect on HeLa cells via apoptosis, and it may be a potential candidate in field of anticancer drug discovery.

Apoptosis↗

Trichostatin A attenuates airway inflammation in mouse asthma model.

BACKGROUND: Histone deacetylase (HDAC) inhibition has been demonstrated to change the expression of a restricted set of cellular genes. T cells are essential in the pathogenesis of allergen-induced airway inflammation. It was recently reported that treatment with HDAC inhibitors induces a T cell-suppressive effect. OBJECTIVE: The purpose of this study was to determine whether treatment with trichostatin A (TSA), a representative HDAC inhibitor, would reduce allergen-induced airway inflammation in a mouse asthma model. METHODS: BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and challenged with an aerosol of OVA. TSA (1 mg/kg body weight) was injected intraperitoneally every 2 days beginning on day 1. Mouse lungs were assayed immunohistochemically for HDAC1, a major HDAC subtype, and for infiltration of CD4+ cells. The effect of TSA on airway hyper-responsiveness (AHR) was determined, and the bronchoalveolar lavage fluid (BALF) of these mice was assayed for the number and types of inflammatory cells, and for the concentrations of IL-4, IL-5, and IgE. RESULTS: HDAC1 was localized within most airway cells and infiltrating inflammatory cells of asthmatic lungs. Treatment with TSA significantly attenuated AHR, as well as the numbers of eosinophils and lymphocytes in BALF. TSA also reduced infiltration of CD4+ and inflammatory cells and mucus occlusions in lung tissue, and decreased the concentrations of IL-4, IL-5, and IgE in BALF. CONCLUSION: TSA attenuated the development of allergic airway inflammation by decreasing expression of the Th2 cytokines, IL-4 and IL-5, and IgE, which resulted from reduced T cell infiltration. Our results suggest that HDAC inhibition may attenuate the development of asthma by a T cell suppressive effect.

Animals↗

Posterior mediastinal paraganglioma with bilateral adrenal pheochromocytoma.

Paraganglioma and adrenal pheochromocytoma are tumors of common origin arising from chromaffin cells. However, it is extremely rare to find mediastinal paraganglioma simultaneously with bilateral adrenal pheochromocytoma. We report a 53-year-old man who was diagnosed with posterior mediastinal paraganglioma and bilateral adrenal pheochromocytoma and who underwent successful excision of the posterior mediastinal mass and bilateral total adrenalectomy.

Adrenal Gland Neoplasms↗

Ca(2+)-induced folding of a family I.3 lipase with repetitive Ca(2+) binding motifs at the C-terminus.

In order to understand a role of the Ca(2+) ion on the structure and function of a Ca(2+)-dependent family I.3 lipase from Pseudomonas sp. MIS38, apo-PML, holo-PML, holo-PML*, and the N-terminal domain alone (N-fragment) were prepared and biochemically characterized. Apo-PML and holo-PML represent refolded proteins in the absence and presence of the Ca(2+) ion, respectively. Holo-PML* represents a holo-PML dialyzed against 20 mM Tris-HCl (pH 7.5). The results suggest that the C-terminal domain of PML is almost fully unfolded in the apo-form and its folding is induced by Ca(2+) binding. The folding of this C-terminal domain may be required to make a conformation of the N-terminal catalytic domain functional.

Amino Acid Motifs↗

Application of nucleotide sequence of RNA polymerase beta-subunit gene (rpoB) to molecular differentiation of serovars of Salmonella enterica subsp. enterica.

To establish a molecular differentiation method for Salmonella enterica subsp. enterica, a hyper-variable region of RNA polymerase beta-subunit (rpoB) of S. enterica subsp. enterica (I), serotype Typhimurium, and Escherichia coli were investigated through comparison of nucleotide sequence of the region. The hyper-variable region was identified at 612-937 of the gene. After PCR amplification of the region in the 17 serotypes and two biotypes of serotype Gallinarum of S. enterica subsp. enterica (I), the nucleotide sequences of the region were determined and compared. All serotypes were distantly related to E. coli with 82.8-84.7% identities in nucleotide sequence while showing 96.6-100% identities with each other. According to the phylogenetic analysis based on the sequenced region with the neighbor-joining method, relatedness of biotype Gallinarum to serotype Enteritidis and biotype Pullorum was determined. Biotype Gallinarum was more closely related to serotype Enteritidis than biotype Pullorum. These results suggested that the 612-937 variable region of rpoB might be useful for molecular evolutionary analysis of serotypes of S. enterica subsp. enterica (I).

Amino Acid Sequence↗

Observability of quantum phase fluctuations in cuprate superconductors.

We study the order parameter phase fluctuation effects in cuprate superconductors near T = 0, using a quasi-two-dimensional d-wave BCS model. An effective phason theory is obtained which is used to estimate the strength of the fluctuations, the fluctuation correction to the in-plane penetration depth, and the pair-field susceptibility. We find that, while the phase fluctuation effects are difficult to observe in the renormalization of the superfluid phase stiffness, they may be observed in a pair tunneling experiment which measures the pair-field susceptibility.

Journal Article↗

Expression of Th2 cytokines decreases the development of and improves Behçet's disease-like symptoms induced by herpes simplex virus in mice.

In the etiology of Behçet's disease (BD), viral infection has long been postulated as a contributing factor, and viral involvement has been demonstrated. However, viral infection alone is not sufficient to explain the pathogenesis of BD, and some evidence suggests that immunologic abnormalities are also important. To study the possible role of immune regulation in the development of BD-like symptoms induced by herpes simplex virus inoculation in ICR mice, macrophages were deleted by use of liposome-encapsulated clodronate (lip-Cl(2)MDP). Treatment with lip-Cl(2)MDP suppressed the development of BD-like symptoms, and this suppression was correlated with the induction of interleukin-4 expression in mouse spleens. When the Th2 adjuvant ovalbumin (OVA)-alum was injected into mice with BD-like symptoms, their cutaneous symptoms improved. Adoptive transfer with splenocytes from OVA-alum-injected mice also resulted in improvement. These findings suggest that up-regulated Th2 cytokine expression can attenuate the development of and improve some BD-like symptoms.

Animals↗

Edge electron states for quasi-one-dimensional organic conductors in the magnetic-field-induced spin-density-wave phases.

We develop a microscopic picture of the electron states localized at the edges perpendicular to the chains in the Bechgaard salts in the quantum Hall regime. In a magnetic-field-induced spin-density-wave state characterized by an integer N, there exist N branches of chiral gapless edge excitations. Localization length is much longer and velocity much lower for these states than for the edge states parallel to the chains. We calculate the contribution of these states to the specific heat and propose a time-of-flight experiment to probe the propagating edge modes directly.

Journal Article↗

Expression of the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1) in the Xenopus embryo.

We have isolated the Xenopus homologue of the receptor for activated C-kinase 1 (RACK1), whose amino acid sequence shows significant similarity with other vertebrate RACK1s. XRACK1 is a maternally expressed gene and its zygotic expression is detected in the antero-dorsal region and dorsal midline in the late neurula. At tailbud stage, rather diffuse staining is seen in the somite and head. Later, XRACK1 mRNA is expressed highly in ventrally migrating abdominal muscle anlagen, where it remains expressed during subsequent stages.

Amino Acid Sequence↗

Phosphorylation of purified recombinant hepatitis B virus-X protein by mitogen-activated protein kinase and protein kinase C in vitro.

The recombinant human hepatitis B virus-X protein (rhHBx) has been expressed as inclusion bodies in Escherichia coli and purified. By sequential dialysis of urea, rhHBx was folded into the native structure, which was demonstrated by both the efficacy of its transcriptional activation of the adenovirus major late promoter, fluorescence and circular dichroism (CD) analysis. The increase in CD values at 220 nm and a corresponding blue shift of the intrinsic fluorescence emission confirmed the ability of HBx to refold in lower concentrations of urea to produce the active protein. After purification and renaturation, the rhHBx protein was found to be phosphorylated by protein kinase C (PKC) and mitogen-activated protein kinase (MAPK). In vivo phosphorylation of HBx was also demonstrated. Although PKC and MAPK enhance the HBx phosphorylation in vitro, neither protein kinase A nor caseine kinase II (CKII) phosphorylate HBx protein, though there are possible substrate residues of both kinases in HBx protein. Phosphoamino acid analysis of the total acid hydrolyzed HBx showed that serine residues can be phosphorylated by PKC or MAPK.

Amino Acid Sequence↗

Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes.

Low oxygen tension influences tumor progression by enhancing angiogenesis; and histone deacetylases (HDAC) are implicated in alteration of chromatin assembly and tumorigenesis. Here we show induction of HDAC under hypoxia and elucidate a role for HDAC in the regulation of hypoxia-induced angiogenesis. Overexpressed wild-type HDAC1 downregulated expression of p53 and von Hippel-Lindau tumor suppressor genes and stimulated angiogenesis of human endothelial cells. A specific HDAC inhibitor, trichostatin A (TSA), upregulated p53 and von Hippel-Lindau expression and downregulated hypoxia-inducible factor-1alpha and vascular endothelial growth factor. TSA also blocked angiogenesis in vitro and in vivo. TSA specifically inhibited hypoxia-induced angiogenesis in the Lewis lung carcinoma model. These results indicate that hypoxia enhances HDAC function and that HDAC is closely involved in angiogenesis through suppression of hypoxia-responsive tumor suppressor genes.

Animals↗

Experimental studies on the antiviral agent famciclovir in Behçet's disease symptoms in ICR mice.

BACKGROUND: Chronic oral aphthae, recurrent genital ulcers and uveitis are the three main manifestations of Behçet's disease (BD). The aetiopathogenesis of BD is still obscure, but herpes simplex virus (HSV) is one of the possible causal factors. Various kinds of drugs, including immunosuppressants and aciclovir have been used in treatment, but effectiveness is variable. OBJECTIVES: To demonstrate the efficacy of famciclovir, an antiviral compound that acts against HSV, varicella-zoster virus and hepatitis B virus, in a murine model of BD. METHODS: Using the HSV-induced BD mouse model, famciclovir was administered variously before and after inoculation or from the day of lesion occurrence, with appropriate controls. Ulceration of the mouth and genital skin and eye involvement were monitored. In addition, spleen cytokine expression was measured by polymerase chain reaction. RESULTS: Pretreatment and concurrent treatment did not affect the occurrence of BD, but treatment from the appearance of lesions was effective in improving BD and preventing recurrence. After famciclovir, interleukin 2 expression correlated with the recurrence of BD symptoms. CONCLUSIONS: This model suggests the possible role of immune response to viral infection in the development and activation of BD. The study provides a rationale for clinical trials of famciclovir in the human form of BD.

2-Aminopurine↗

1,2-bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid induces caspase-mediated apoptosis and reactive oxygen species-mediated necrosis in cultured cortical neurons.

Sustained alteration in [Ca(2+)]i triggers neuronal death. We examined morphological and signaling events of Ca(2+)-deficiency-induced neuronal death. Cortical cell cultures exposed to 20 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, underwent neuronal apoptosis within 12 h that was evident by shriveled cell bodies, aggregated and condensed nuclear chromatin, and disrupted nuclear membrane. Thereafter, surviving neurons revealed typical necrosis, accompanied by swelling of cell body and mitochondria, over 24 h. Both apoptosis and necrosis were prevented by inclusion of 1 microg/mL cycloheximide, a protein synthesis inhibitor. Treatment with BAPTA-AM induced translocation of Bax into mitochondria within 4 h and release of cytochrome c from mitochondria over 4-12 h. An active fragment of caspase-3, a downstream mediator of cytochrome c, was observed within 8 h and cleaved PHF-1-positive tau. Administration of zVAD-fmk, a broad inhibitor of caspases, or DEVD-amc, a selective inhibitor of caspase-3, selectively prevented the apoptosis component of BAPTA-AM neurotoxicity. In contrast, BAPTA-AM-induced necrosis was propagated through sequential production of superoxide, mitochondrial and cytoplasmic reactive oxygen species. Combined treatment with caspase inhibitors and antioxidants blocked BAPTA-AM neurotoxicity. The present study suggests that neurons deficient in [Ca(2+)]i undergo caspase-3-mediated apoptosis and reactive oxygen species (ROS)-mediated necrosis.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Age-related increase of brain cyclooxygenase activity and dietary modulation of oxidative status.

Several studies have demonstrated that inhibitors of cyclooxygenase (COX) attenuate various neuronal injuries and age-dependent demented conditions. From these findings, we proposed to test the effect of age on COX activity and its possible suppression by the antiaging action of dietary restriction in the rat brain. The status of reactive oxygen species (ROS) was also assessed to correlate with COX activity to delineate the underlying mechanism of the altered COX activity during aging. These results showed that COX activity significantly increased in 24-month-old rats compared with 6-month-old rats in an ad libitum group. Interestingly, mRNA and protein levels of COX-2 showed little corresponding age-related change. The formation of ROS was found to increase gradually with age in ad libitum fed rats. However, dietary restriction suppressed the increase at the age of 24 months. To substantiate the relationship between ROS and COX activity when the rats were 24 months of age, we conducted in vitro experiments with a C6 glioma cell line. Together, it is concluded that increased COX activity with age is due to the activation of COX catalytic reaction by ROS without increased gene expression of COX-2 and that it is related to the increased pro-oxidant status in aged rats.

Age Factors↗

Effects of ambient air pollution on daily mortality in a cohort of patients with congestive heart failure.

This study was planned to test the hypothesis that patients with congestive heart failure are more susceptible to the harmful effects of ambient air pollution than the general population. We used both general additive Poisson regression and the case-crossover approach to test the hypothesis. The effect of air pollution on daily mortality of patients with congestive heart failure among residents of Seoul, South Korea, during the period 1994--1998 was compared with that of the general population in the same area and the same period. The odds ratios and 95% confidence intervals (95% CIs) estimated from general additive models in the general population for an interquartile range increase of particulate matter less than 10 microm in diameter (42.1 microg/m(3)), carbon monoxide (0.59 ppm), nitrogen dioxide (14.6 ppb), sulfur dioxide (9.9 ppb), and ozone (20.5 ppb) were 1.014 (95% CI = 1.006- 1.022), 1.022 (95% CI = 1.017- 1.029), 1.021 (95% CI = 1.014- 1.029), 1.020 (95% CI = 1.012--1.028), and 1.010 (95% CI = 1.002--1.017), respectively. The estimated effects appeared larger among the congestive heart failure patients than among the general population (2.5 approximately 4.1 times higher depending on the pollutants). The results from the case-crossover analysis were similar. The finding of a stronger association in the patients with congestive heart failure reinforces the evidence that a harmful effect of air pollution is mediated by cardiovascular mechanisms.

Adult↗

Expression profile of histone deacetylase 1 in gastric cancer tissues.

Although histone deacetylases (HDACs) appear to play a crucial role in carcinogenesis, the expression status of HDACs in primary human cancer tissues has not yet been reported. In this study, we investigated the expression level of HDAC1 in 25 paired primary human gastric cancer (GC) tissues and corresponding normal tissues through semi-quantitative RT-PCR and immunoblot analysis. The HDAC1 expression pattern was also topologically examined through immunohistochemistry. Overexpression of HDAC1 mRNA was detected in 68% of GC tissues (17 of 25), and the relative density of HDAC1 mRNA in GC tissue was increased 1.8-fold versus the normal counterpart (P < 0.01). Elevated expression of HDAC1 protein was also detected in 61% of GC samples (11 of 18), which also showed an increased mRNA level of HDAC. Immunohistochemically, overexpression of HDAC1 was predominantly localized in the nuclei of most neoplastic cells, including embolic tumor cells, whereas normal glandular epithelial cells revealed only weak HDAC1 expression that was focal in distribution. Thus, the present study clearly demonstrates that HDAC1 is overexpressed in GC and probably plays a significant role in gastric carcinogenesis.

Blotting, Western↗

Molecular authentication of Panax ginseng species by RAPD analysis and PCR-RFLP.

In order to develop convenient and reproducible methods for the identification of ginseng drugs at a DNA level, randomly amplified polymorphic DNA (RAPD) and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses were applied within Panax species. To authenticate Panax ginseng among ginseng populations, RAPD analysis was carried out using a 20 mer-random primer. The similarity coefficients among the DNA of ginseng plants analyzed were low, ranging from 0.197 to 0.491. In addition, by using PCR-RFLP analysis, very different fingerprints were obtained within Korean ginseng plants. These results suggest that these methods are able to authenticate the concerned Panax species. Broader application of this approach to authenticate other morphologically similar medicinal materials is rationalized.

DNA, Plant↗