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Biomedical subjects

Seung H Kim

Publications and source records attributed to Seung H Kim.

14 recordsLinked to original sources

Anti-CD3 single-chain Fv/interleukin-18 fusion DNA induces anti-mycobacterial resistance via efficient interferon-gamma production in BALB/c mice infected with Mycobacterium avium.

T helper type 1 (Th1) cell-mediated immune response performs a critical role in the induction of host defenses against a variety of intracellular pathogens. We recently demonstrated that the linkage between interleukin (IL)-18 and anti-CD3sFv genes confined the effect of IL-18 to the CD3+ T cells, resulting in the efficient induction of Thl immune responses. In this study, we attempted to determine whether the anti-CD3 single-chain Fv/IL-18 fusion DNA (pAnti-CD3sFv/IL-18) could stimulate resistance to Mycobacterium avium infection in genetically susceptible BALB/c mice. Immunization with pAnti-CD3sFv/IL-18 DNA during intranasal infection with M. avium resulted in a significant reduction in the bacterial load in the lung throughout the entire 10-week observation period. Immunization with pAnti-CD3sFv/IL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by the lung cells, as compared with the injection of pAnti-CD3sFv DNA, or of a simple mixture of pAnti-CD3sFv DNA and pIL-18 DNA. Furthermore, the lung cells of the mice injected with pAnti-CD3sFv/IL-18 DNA exhibited persistent production of IFN-gamma. Treatment with anti-IFN-gamma antibody resulted in an abrogation of anti-mycobacterial effects in mice injected with pAnti-CD3sFv/IL-18 DNA. These results indicate that vaccination with the pAnti-CD3sFv/IL-18 fusion DNA induces significant resistance to M. avium infection, via the production of IFN-gamma in CD4+ T cells.

Adjuvants, Immunologic↗

Induction of human leukemia HL-60 cell differentiation via a PKC/ERK pathway by helenalin, a pseudoguainolide sesquiterpene lactone.

Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits nuclear factor-kappa B (NF-kappa B) DNA binding activity. In this report, we investigated the effect of helenalin on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Helenalin by itself markedly induced HL-60 cell differentiation in a concentration-dependent manner. Cytofluorometric analysis and cell morphologic studies indicated that helenalin induced cell differentiation predominantly into granulocytes. Protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by helenalin, while p38 mitogen-activated protein kinase (MAPK) inhibitors did not. Moreover, helenalin enhanced PKC activity and protein level of PKC beta I and PKC beta II isoforms, and also increased the level of pERK in a concentration-dependent manner. In addition, the enhanced levels of cell differentiation closely correlated with the decreased levels of NF-kappa B binding activity by helenalin. These results indicate that PKC, ERK, and NF-kappa B may be involved in HL-60 cell differentiation induced by helenalin.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Open vs. closed hemorrhoidectomy.

PURPOSE: This prospective, randomized, clinical trial compared the outcome of surgical hemorrhoidectomy by open and closed techniques in terms of postoperative pain, wound healing, and morbidity. METHODS: All consecutive patients with Grade III internal hemorrhoids with prominent external components or Grade IV hemorrhoids were randomly allocated to one of two groups. The entire wound was left open in the open group and completely closed using 5-0 chromic sutures in the closed group. Postoperative pain was assessed by a linear analog scale. Additional consumption of oxycodone hydrochloride on the day of surgery and at defecation during the first week was recorded. Patients were followed up 1, 2, and 3 weeks after the procedure. RESULTS: There were 40 patients in each group. Pain score at recovery from the anesthesia was significantly lower in the closed group (P < 0.05). Altogether, 15 percent of patients in the closed group required additional oxycodone hydrochloride for pain compared to 45 percent in the open group (P < 0.01). The pain score at the first bowel movement was significantly lower in the closed group (P < 0.01). Wound healing was significantly faster in the closed group: 75 percent of patients in the closed group had healed at 3 weeks after the procedure compared to 18 percent in the open group (P < 0.001). CONCLUSIONS: The closed technique is more advantageous with respect to less pain during the early postoperative period and faster wound healing.

Adult↗

Effects of activated carbon types and service life on removal of endocrine disrupting chemicals: amitrol, nonylphenol, and bisphenol-A.

Removal performances of endocrine disrupting chemicals (EDC) such as amitrol, nonylphenol, and bisphenol-A were evaluated in this study using granular activated carbon (GAC) adsorption. This study found that GAC adsorption was effective in removal of EDCs with high K(ow) value. Nonylphenol and bisphenol-A were effectively adsorbed onto all carbons (including the used carbons) tested in this study. As indicated by K(ow) value, nonylphenol was more effectively adsorbed than bisphenol-A. The coal-based carbon was found more effective than other carbons in the adsorption of nonylphenol and bisphenol-A due to its larger pore volume. The adsorption capacity reduced with the operation year, and the extent of the reduction was different depending upon the carbon type and the operation year. Amitrol was effectively removed by biological degradation, but was poorly adsorbed. Since the microbes residing at the used carbons already accustomed to amitrol, the used carbons removed amitrol better than the virgin carbons. Although the coal-based carbon showed the best removal performance of amitrol, GAC adsorption could not be recommended for amitrol removal because considerable portion of incoming amitrol (9-87%) passed through GAC adsorption column. According to this study, pore volume mainly influenced the adsorption capacity, but the surface charge was also important due to electrical interaction. The adsorption parameters for nonylphenol and bisphenol-A provided by this study could be valuable when GAC adsorption was considered to handle an accidental spill of nonylphenol and bisphenol-A.

Adsorption↗

Formononetin, a phyto-oestrogen, and its metabolites up-regulate interleukin-4 production in activated T cells via increased AP-1 DNA binding activity.

Phyto-oestrogens are polyphenolic non-steroidal plant compounds with oestrogen-like biological activity. Phyto-oestrogens have many biological effects including oestrogen agonist/antagonist properties. However, the effect of phyto-oestrogens on allergic responses remains unclear. In this study we investigated whether formononetin, a phyto-oestrogen, and its metabolites, daidzein and equol, affect production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune response, in primary CD4+ T cells and EL4 T lymphoma cells. Formononetin, daidzein and equol significantly enhanced IL-4 production from both CD4+ T cells and EL4 cells in a dose-dependent manner. Formononetin, daidzein and equol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 gene promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of P4 site carrying nuclear factor of activated T cells (NF-AT) and activator protein-1 (AP-1) binding sites. In addition, formononetin, daidzein and equol increased AP-1 DNA binding activities while did not affect NF-AT DNA binding activities. The enhancing effects on IL-4 production and AP-1 DNA binding activities were abrogated by specific inhibitors for phosphatidylinositol-3-kinase (PI3K), protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK), indicating that formononetin, daidzein and equol might enhance IL-4 production by increased activation of AP-1 through the PI3-K/PKC/p38 MAPK signalling pathway. These results suggest that phyto-oestrogens and some of their metabolites may increase allergic responses via the enhancement of IL-4 production in T cells.

Animals↗

Epigallocatechin gallate prevents oxidative-stress-induced death of mutant Cu/Zn-superoxide dismutase (G93A) motoneuron cells by alteration of cell survival and death signals.

This study was undertaken to evaluate the effect of the G93A mutation in the human Cu/Zn-superoxide dismutase gene (hSOD1) on the phosphatidylinositol-3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3) pathway in motoneuron, and to determine the role of epigallocatechin gallate (EGCG) on oxidative stress-injured motoneurons. The viability of G93A mutant cells was less than that of wild-type cells, and the activation of PI3K and the phosphorylation of Akt and GSK-3 in G93A mutant cells decreased compared with wild-type hSOD1 4.1 cells. In the experiment to evaluate the effect of oxidative stress and/or EGCG on these motoneurons, after exposure to 400 microM H2O2, the MTT assay revealed greatly reduced viability of G93A mutant cells compared with wild-type cells, and pre-treatment of these cells with EGCG before H2O2 exposure increased the viability of both cell lines. Western blot analysis showed that the G93A mutation and oxidative stress decreased survival signals including PI3K/Akt but increased death signals including GSK-3; however, pre-treatment with EGCG increased survival signals but decreased death signals. These results suggest that PI3K/Akt and GSK-3 activities are altered in G93A mutant cells and EGCG-induced activation of PI3K/Akt and inhibition of GSK-3 could be a new potential therapeutic strategy for ALS associated with oxidative injury.

Apoptosis↗

Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue.

Dendritic cells are potent antigen-presenting cells that initiate and amplify immune responses. To determine whether dendritic cells participate in inflammatory reactions in amyotrophic lateral sclerosis (ALS), we examined mRNA expression of dendritic cell surface markers in individual sporadic ALS (sALS), familial ALS (fALS), and nonneurological disease control (NNDC) spinal cord tissues using semiquantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Immature (DEC205, CD1a) and activated/mature (CD83, CD40) dendritic cell transcripts were significantly elevated in ALS tissues. The presence of immature and activated/mature dendritic cells (CD1a(+) and CD83(+)) was confirmed immunohistochemically in ALS ventral horn and corticospinal tracts. Monocytic/macrophage/microglial transcripts (CD14, CD18, SR-A, CD68) were increased in ALS spinal cord, and activated CD68(+) cells were demonstrated in close proximity to motor neurons. mRNA expressions of the chemokine MCP-1, which attracts monocytes and myeloid dendritic cells, and of the cytokine macrophage-colony stimulating factor (M-CSF) were increased in ALS tissues. The MCP-1 protein was expressed in glia in ALS but not in control tissues and was increased in the CSF of ALS patients. Those patients who progressed most rapidly expressed significantly more dendritic transcripts than patients who progressed more slowly. These results support the involvement of immune/inflammatory responses in amplifying motor neuron degeneration in ALS.

Adult↗

Phosphatidylinositol-3 kinase/Akt and GSK-3 mediated cytoprotective effect of epigallocatechin gallate on oxidative stress-injured neuronal-differentiated N18D3 cells.

Epigallocatechin gallate (EGCG) is one of most famous compounds of green tea. EGCG suppresses apoptosis induced by oxidative radical stress through several mechanisms. This study was designed to investigate whether EGCG plays a cytoprotective role by activating phosphatidylinositol-3 kinase (PI3K)/Akt-dependent anti-apoptotic pathway and inhibiting glycogen synthase kinase-3 (GSK-3) activity in oxidative stressed N18D3 neural cells. N18D3 cells, mouse neuroblastoma X dorsal root ganglion hybrid cell line, were pre-treated with EGCG or z-VAD-fmk, non-selective caspase inhibitor used as a control substance, for 2 h. The N18D3 cells were then exposed to low concentration of H(2)O(2) (100 microM) for 30 min, and further incubated for 24 h. MTT (3,[4,5-dimethylthiazol]-2-yl) assay and trypan blue staining were used to identify cell viability. Immunoreactivity (IR) of PI3K, Akt, and GSK-3 beta were measured by Western blotting. MTT assay and trypan blue staining showed that EGCG and z-VAD-fmk significantly increased cell viability, and IR of PI3K, phospho-Akt and phospho-GSK-3 beta was significantly increased in the cells treated with EGCG, but not in z-VAD-fmk treated. These results imply that EGCG has neuroprotective effect by increasing PI3K/Akt-dependent anti-apoptotic signals.

Amino Acid Chloromethyl Ketones↗

Evaluation of compressed video-images for emergency telemedicine work with trauma patients.

Video-encoders in telemedicine systems need to adjust their coding methods for operation on heterogeneous networks on which bandwidth fluctuates. We evaluated MPEG-4 compressed video-pictures of three trauma patients. We compared the original video-frames with compressed video-frames in terms of the peak signal-to-noise ratio (PSNR). In a qualitative evaluation, three emergency specialists scored the quality of the video-images blind, on a five-point scale (1= bad to 5 = excellent). The PSNR increased as the bit rate increased from 0.2 to 6 Mbit/s. When the bit rate was fixed, in other words at a given network bandwidth, a higher PSNR was obtained at the expense of spatial resolution and frame rate. The video quality was highly affected by the amount of camera shake. Emergency telemedicine systems require a high bit rate, high spatial resolution and a high frame rate to achieve optimum video quality. However, if the bandwidth is limited (i.e. the bit rate is fixed), temporal resolution becomes more important than spatial resolution.

Data Compression↗

Epigallocatechin gallate protects nerve growth factor differentiated PC12 cells from oxidative-radical-stress-induced apoptosis through its effect on phosphoinositide 3-kinase/Akt and glycogen synthase kinase-3.

The effects of epigallocatechin gallate (EGCG) on the phosphoinositide 3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3) pathway during oxidative-stress-induced injury were studied using H2O2-treated PC12 cells, which were differentiated by nerve growth factor (NGF). Following 100 microM H2O2 exposure, the viability of differentiated PC12 cells (EGCG or z-VAD-fmk pretreated vs. not pretreated) was evaluated the number of viable cell with Trypan blue and 3,4,5-dimethylthiazol-2-yl (MTT). Additionally, expression of cytochrome c, caspase-3, poly(ADP-ribose) polymerase (PARP), PI3K/Akt and GSK-3 was examined using Western blot analyses. EGCG or z-VAD-fmk-pretreated PC12 cells showed an increase of viability compared to untreated PC12 cells, and pretreatment of PC12 cells with either agent induced a dose-dependent inhibition of caspase-3 activation and PARP cleavage. However, inhibition of cytochrome c release was only detected in EGCG-pretreated cells. Upon examination of the PI3K/Akt and GSK-3 upstream pathway, Western blots of EGCG pretreated cells showed decreased immunoreactivity (IR) of Akt and GSK-3 and increased IR of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3. In contrast, no changes were seen in z-VAD-fmk-pretreated cells. These results show that EGCG affects the PI3K/Akt, GSK-3 pathway as well as downstream signaling, including the cytochrome c and caspase-3 pathways. Therefore, it is suggested that EGCG-mediated activation of PI3K/Akt and inhibition of GSK-3 could be a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.

Animals↗

Induction of interleukin-12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1 response.

In this study we investigated whether berberine-mediated induction of interleukin-12 (IL-12) production in antigen-presenting cells could regulate a cytokine profile of antigen-primed CD4+ T helper (Th) cells. Pretreatment with berberine induced IL-12 production in both macrophages and dendritic cells, and significantly increased the levels of IL-12 production in lipopolysaccharide-stimulated macrophages and in CD40 ligand-stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon-gamma (IFN-gamma) and reduced their ability to induce IL-4 in antigen-primed CD4+ T cells. Berberine did not influence the macrophage cell surface expression of the class II major histocompatibility complex molecule, the co-stimulatory molecules CD80 and CD86, and intracellular adhesion molecule-1. Addition of neutralizing anti-IL-12p40 monoclonal antibody to cultures of berberine-pretreated macrophages and CD4+ T cells restored IL-4 production in antigen-primed CD4+ T cells. The in vivo administration of berberine resulted in the enhanced induction of IL-12 production by macrophages when stimulated in vitro with lipopolysaccharide or heat-killed Listeria monocytogenes, leading to the inhibition of the Th type 2 cytokine profile (decreased IL-4 and increased IFN-gamma production) in antigen-primed CD4+ T cells. These findings may point to a possible therapeutic use of berberine or medicinal plants containing berberine in the Th type 2 cell-mediated immune diseases such as allergic diseases.

Animals↗

PARP expression is increased in astrocytes but decreased in motor neurons in the spinal cord of sporadic ALS patients.

The evidence for increased oxidative stress and DNA damage in amyotrophic lateral sclerosis (ALS) prompted studies to determine if the expression of poly(ADP-ribose) polymerase (PARP) is increased in ALS. Using Western analyses of postmortem tissue, we demonstrated that PARP-immunoreactivity (PARP-IR) was increased 3-fold in spinal cord tissues of sporadic ALS (sALS) patients compared with non-neurological disease controls. Despite the increased PARP-IR, PARP mRNA expression was not increased significantly. Immunohistochemical analyses revealed PARP-IR was increased in both white and gray matter of sALS spinal cord. While PARP-IR was predominantly seen in astrocytes, large motor neurons displayed reduced staining compared with controls. This result contrasts sharply to the staining of Alzheimer and MPTP-induced Parkinson diseased tissue, where poly(ADP-ribose) (PAR)-IR was seen mostly in neurons, with little astrocytic staining. PARP-IR was increased in the pellet fraction of sALS homogenates compared with control homogenates, representing potential PARP binding to chromatin or membranes and suggesting a possible mechanism of PARP stabilization. The present results demonstrate glial alterations in sALS spinal cord tissue and support the role of glial alterations in sALS pathogenesis. Additionally, these results demonstrate differences in sALS spinal motor neurons and astrocytes compared to brain neurons and astrocytes in Alzheimer disease and MPTP-induced Parkinson disease despite the presence of markers for oxidative stress in all 3 diseases.

Adult↗

Anomalous magnetic properties of MnO nanoclusters.

In this communication, we experimentally report, for the first time, that the MnO nanoclusters with cluster diameters of 5-10 nm show a ferromagnetic behavior with a phase transition from ferromagnetic to paramagnetic phases at 27 K even though their bulk phase is antiferromagnetic. We observed large coercivities up to 9500 Oe and a large remanence of 1.72 emu/g at 2 K, which are typically observed values for ferromagnetic materials. Although it is not clear, this abnormal ferromagnetic behavior of MnO nanoclusters may arise from cluster size effects.

Journal Article↗

Potentiation of 1,25-dihydroxyvitamin D(3)-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone.

Costunolide, a germacranolide sesquiterpene lactone that exists in several medicinal plants, is known to be a possible anti-cancer and chemopreventive agent for tumorigenesis. In this report, we investigated the effect of costunolide on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with 5nM 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)). Costunolide by itself had very weak effects on the differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic studies indicated that costunolide potentiated 1,25-(OH)(2)D(3)-induced cell differentiation predominantly into monocytes. Inhibitors for PKC, PI3-K, and ERK markedly inhibited HL-60 cell differentiation induced by costunolide in combination with 1,25-(OH)(2)D(3). In addition, pretreatment of HL-60 cells with costunolide before the 1,25-(OH)(2)D(3) addition also potentiated cell differentiation in a concentration- and time-dependent manner, and the enhanced levels of cell differentiation closely correlated with the inhibitory levels of NF-kappaB-binding activity by costunolide. These results indicate that PKC, PI3-K, ERK and NF-kappaB may be involved in 1,25-(OH)(2)D(3)-mediated cell differentiation enhanced by costunolide.

Antineoplastic Agents, Phytogenic↗