Biomedical subjects

Eung Seok Lee

Publications and source records attributed to Eung Seok Lee.

At least 19 recordsLinked to original sources

PubMed2006

Characteristics and applications of controlled-release KMnO4 for groundwater remediation.

In situ chemical oxidation (ISCO) using potassium permanganate (KMnO4) has been widely used as a practical approach for remediation of groundwater contaminated by chlorinated solvents like trichloroethylene. The most common applications are active flushing schemes, which target the destruction of some contaminant source by injecting concentrated permanganate (MnO4(-)) solution into the subsurface over a short period of time. Despite many promising results, KMnO4 flushing is often frustrated by inefficiency associated with pore plugging by MnO2 and bypassing. Opportunities exist for the development of new ISCO systems based on KMnO4. The new scheme described in this paper uses controlled-release KMnO4 (CRP) as an active component in the well-based reactive barrier system. This scheme operates to control spreading of a dissolved contaminant plume. Prototype CRP was manufactured by dispersing fine KMnO4 granules in liquid crystal polymer resin matrix. Scanning electron microscope data verified the formation of micro-scale (ID=20-200 microm) secondary capillary permeability through which MnO4(-) is released by a reaction-diffusion process. Column and numerical simulation data indicated that the CRP could deliver MnO4(-) in a controlled manner for several years without replenishment. A proof-of-concept flow-tank experiment and model simulations suggested that the CRP scheme could potentially be developed as a practical approach for in situ remediation of contaminated aquifers. This scheme may be suitable for remediation of sites where accessibility is limited or some low-concentration contaminant plume is extensive. Development of delivery systems that can facilitate lateral spreading and mixing of MnO4(-) with the contaminant plume is warranted.

Hydrocarbons, Chlorinated↗

PubMed2006

Determination of 1-furan-2-yl-3-pyridin-2-yl-propenone, an anti-inflammatory propenone compound, by high performance liquid chromatography with ultraviolet spectrometry.

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity. In the present study, pharmacokinetic parameters for FPP-3 and its metabolites were determined at the same time by using high-performance liquid chromatography-ultraviolet spectrometry. Two metabolites were detected in sera when FPP-3 was administered intravenously to male SD rats. The linearity of FPP-3, M1 (1-furan-2-yl-3-pyridin-2-yl-propan-1-one) and M2 (1-furan-2-yl-3-pyridin-2-yl-propan-1-ol) was confirmed in the concentration ranges of 0.5-20, 0.101-4.04 and 1.04-20.4 microg/ml, respectively. The lower limits of quantitation of FPP-3, M1 and M2 were 0.5, 0.1 and 1.0 microg/ml, respectively. The intra- and inter-day precision and accuracy over the concentration range of target compounds were within 13.5 and 14.2%, respectively. The half-lives of FPP-3, M1 and M2 were 16.3, 27.7 and 22.1 min, respectively.

Animals↗

PubMed2006

Cytotoxicity and DNA topoisomerase inhibitory activity of constituents isolated from the fruits of Evodia officinalis.

Four alkaloids (1-4), three quinolone alkaloids (5-7), and three flavanoid glucosides (8-10) were isolated from the fruits of Evodia officinalis Dode, and their structures were determined from chemical and spectral data. Compounds, 3, 8, 9 and 10 were isolated from this plant for the first time. Of these compounds, 1-3 and 5-7 exhibited moderate cytotoxicities against cultured human colon carcinoma (HT-29), human breast carcinoma (MCF-7), and human hepatoblastoma (HepG-2). Compound 8 showed strong inhibitory effects on DNA topoisomerases I and II (70 and 96% inhibition at a concentration of 20 microM, respectively).

Alkaloids↗

PubMed2006

A new stilbene glucoside from the roots of Polygonum multiflorum Thunb.

One new stilbene glucoside (6), along with five known compounds (1-5), were isolated from the roots of Polygonum multiflorum Thumb., and their chemical structures established based on physicochemical and spectroscopic data. Of the compounds, compound 3 showed DNA topoisomerase I and II inhibitory activities.

Antineoplastic Agents, Phytogenic↗

PubMed2006

Identification of 1-furan-2-yl-3-pyridin-2-yl-propenone, an antiinflammatory agent, and its metabolites in rat liver subcellular fractions.

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has been characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide and tumor necrosis factor-alpha. In the present studies, the phase 1 metabolism of FPP-3 was investigated in rat liver microsomes and cytosols. When FPP-3 was incubated with rat liver microsomes and cytosols in the presence of NADPH, 2 major peaks were detected on a liquid chromatography/electrospray ionization-mass spectrometry. Two metabolites (i.e., M1 and M2) were characterized as reduced forms on propenone: M1 (1-furan-2-yl-3-pyridin-2-yl-propan-1-one) was the initial metabolite and M2 (1-furan-2-yl-3-pyridin-2-yl-propan-l-ol) was a secondary alcohol believed to be formed from M1.

Animals↗

PubMed2006

Calretinin, CD34, and alpha-smooth muscle actin in the identification of peritoneal invasive implants of serous borderline tumors of the ovary.

The correct identification of invasive implants in the peritoneum in serous borderline tumors (SBTs) of the ovary is an important determinant of diagnosis, treatment, and prognosis. Although the histologic criteria to distinguish noninvasive from invasive implants have been defined, the distinction can still be difficult. We examined the presence and distribution of mesothelial cells, stromal fibrocytes, and myofibroblasts in invasive and noninvasive peritoneal implants in 100 noninvasive, 100 invasive, and 100 metastatic nests/foci from 20 cases of SBTs with peritoneal implants, 10 serous carcinomas with peritoneal metastasis, and 10 cases of endosalpingiosis by immunostaining for calretinin, CD34, and alpha-SMA. All 100 invasive nests from seven SBTs and all 100 metastatic nests from the cases of serous carcinoma showed loss of calretinin+ mesothelial cells and stromal CD34+ fibrocytes around the nests. In contrast, 72/100 noninvasive nests displayed the presence of mesothelial cells around the nests and 68 displayed preservation of surrounding stromal fibrocytes. Alpha-smooth muscle actin positive myofibroblasts were present as a stromal response in 100/100 metastatic nests, 100/100 invasive nests and 54/100 noninvasive nests. The loss of mesothelial cells and stromal fibrocytes surrounding invasive nests together with a proliferation of myofibroblasts as demonstrated by immunostaining proved to be a sensitive and specific tool to separate invasive from noninvasive implants and represents an important adjunct to morphologic diagnosis. Combined sensitivity and specificity of the three antibodies was 100 and 81%, respectively. These methods, however, may not be helpful for small biopsies of noninvasive desmoplastic implants. The distribution of these cells provides some insights into the histogenesis of invasive and noninvasive implants in SBTs.

Actins↗

PubMed2006

BRAF mutation and AKAP9 expression in sporadic papillary thyroid carcinomas.

AIM: We aimed to determine the BRAF mutation and AKAP9 expression in papillary thyroid carcinomas (PTCs). METHODS AND RESULTS: In this study, we analysed 100 sporadic PTC specimens and we detected mutation in 62.2% of the conventional type PTCs (51/82), in 50% of the follicular variant type PTCs (3/6), in 50% of the diffuse sclerosing variant type PTCs (1/2), and in 30% of the microcarcinomas (3/10). All mutations involved a T-->A transversion at the nucleotide 1796. The cases with BRAF mutation were significantly associated with extrathyroidal extension. We also evaluated the expression of AKAP9 protein by immunohistochemistry. The AKAP9 protein was seen as a single perinuclear dot in all the PTCs. Therefore, 58% of the specimens harboured the BRAF mutation and no case had AKAP9-BRAF fusion in the sporadic PTCs. CONCLUSION: Our results suggest that the BRAF mutation can be a useful diagnostic and prognostic marker and a target for exploring novel cancer therapies to treat PTCs. AKAP9-BRAF fusion may be a very rare event in sporadic PTCs.

A Kinase Anchor Proteins↗

PubMed2006

Ovarian sclerosing stromal tumor presenting as Meigs' syndrome with elevated CA-125.

Meigs' syndrome caused by sclerosing stromal tumor is extremely rare and only two cases have been reported to date. An elevated serum level of CA-125 is also unusual and it has been thought that it is the consequence of physical irritation and inflammation. In this report, we present the case of a 50-year-old postmenopausal woman with a sclerosing stromal tumor presenting with Meigs' syndrome and an elevated CA-125 level (1476.8 IU/mL). This case highlights the difficulty in discerning the diagnosis of Meigs' syndrome from that of an ovarian malignancy and it should be considered in the differential diagnosis in postmenopausal patients with pelvic mass, ascites, pleural effusions and elevated serum CA-125.

CA-125 Antigen↗

PubMed2006

The effect of 1-furan-2-yl-3-pyridine-2-yl-propenone on pharmacokinetic parameters of theophylline.

The pharmacokinetic parameters of theophylline in rats did not change significantly when the drug was intravenously administered after three consecutive days of pretreatment with 17 mg/kg, orally, of 1-furan-2-yl-3-pyridine-2-yl-propenone (FPP-3), an investigatory drug having dual inhibitory action on cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). However, significant changes were found in the pharmacokinetic parameters of the drug at doses of 34 mg/kg and more of FPP-3. Results of cytochrome P450 activity test indicated that the alteration in pharmacokinetic parameters of the drug appears to be due to the inhibitory effect of FPP-3 on cytochrome P450 1A which is responsible for the metabolism of theophylline. Methoxyresorufin-O-demethylase (MROD) and ethoxyresorufin-O-deethylase (EROD) activity assays revealed that the relative activities of cytochrome P450 1A1 and 1A2 were dose-dependently reduced in the presence of 1, 5, and 10 microM FPP-3 concentrations. Taking into consideration that FPP-3 is intended to be primarily used by geriatric patients with chronic diseases and therefore may be used in long-term basis, the investigatory drug needs to be assessed thoroughly in terms of drug interaction with other commonly prescribed medications.

Animals↗

PubMed2006

nm23-H1 protein expression and gene mutation in 150 patients with non-Hodgkin's lymphomas.

The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL-BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.

Base Sequence↗

PubMed2005

Role of metabolism in parathion-induced hepatotoxicity and immunotoxicity.

The objective of this study was to investigate whether metabolic activation of parathion by cytochrome P-450s (CYPs) was responsible for pesticide-induced hepatotoxicity and immunotoxicity. Initially, to investigate parathion metabolism in vitro, the production of paraoxon and p-nitrophenol, major metabolites of parathion, was determined by high-performance liquid chromatography (HPLC). Subsequently, metabolic fate and CYP enzymes involved in the metabolism of parathion were partially monitored in rat liver microsomes in the presence of the NADPH-generating system. Among others, phenobarbital (PB)-induced microsomes produced the metabolites paraoxon and p-nitrophenol to the greatest extent, indicating the involvement of CYP 2B in parathion metabolism. When female BALB/c mice were treated orally with 1, 4, or 16 mg/kg of parathion in corn oil once, parathion suppressed the antibody response to sheep red blood cells. To further investigate a possible role of metabolic activation by CYP enzymes in parathion-induced toxicity, female BALB/c mice were pretreated intraperitoneally with 40 mg/kg PB for 3 d, followed by a single oral treatment with 16 mg/kg parathion. PB pretreatment produced a decrease in hepatic glutathione content and increases in hepatotoxic paramenters in parathion-treated mice with no changes in the antibody response. In addition, greater p-nitrophenol amounts were produced when mice were pretreated with PB, compared to treatment with parathion alone. These results indicate that parathion-induced hepatotoxicity might be differentiated from immunotoxicity in mice.

Alanine Transaminase↗

PubMed2005

Methoxychlor-induced inducible nitric oxide synthase and proinflammatory cytokines expression in macrophages via NF-kappaB, ERK, and p38 mitogen-activated protein kinases.

Methoxychlor (MXC) is a pesticide that was developed as a replacement for dichlorodiphenyltrichloroethane. The influence of MXC on cytokine production or the functions of macrophages is unclear. This study examined the effects of MXC on the production of nitric oxide (NO) and the proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and analyzed the molecular mechanism in mouse macrophages. The addition of MXC to macrophages induced the production of NO and proinflammatory cytokines and expression levels of these genes in a dose-dependent manner. The NF-kappaB sites were identified in the promoter of the iNOS and proinflammatory cytokines genes. The transient expression and electrophoretic mobility shift assays revealed that the NF-kappaB transcription factor mediated the MXC-induced increase in the iNOS and proinflammatory cytokines expression levels. In addition, MXC induced the rapid phosphorylation of the ERK1/2 and p38 MAPK. This demonstrates that MXC stimulates the production of NO and proinflammatory cytokines and can up-regulate the expression levels of these genes via NF-kappaB transactivation and ERK1/2 and p38 MAPK phosphorylation. Overall, this study provides evidence showing that MXC has inflammatory potential that is previously unrecognized immunomodulating activity.

Animals↗

PubMed2005

Epstein-Barr virus infection in sarcomatoid renal cell carcinoma tissues.

OBJECTIVE: To determine whether Epstein-Barr virus (EBV) infection is related to renal cell carcinoma (RCC) tissues. MATERIALS AND METHODS: We investigated EBV infection and its genotypes in 73 cases of different types of RCC and 18 of non-neoplastic kidney. EBV infection and its genotypes were determined by EBV-encoded RNAs in situ hybridization (EBER-ISH) and polymerase chain reactions for EBV-encoded nuclear antigen 1 (EBNA-1) and EBNA-3C. The immunophenotype and EBV status of the EBV-infected cells were examined by double-labelling of EBER-ISH and/or immunohistochemistry for lymphoid cell markers, EBV proteins, and CD21. RESULTS: EBER-ISH signals were detected in five of 73 RCC tissues (6.8%), but in none of 18 non-neoplastic kidneys. Interestingly, EBER-ISH was positive only in five of the 10 sarcomatoid RCCs, and of these, four also showed amplification of EBNA-1. EBV was located exclusively in the tumour-infiltrating B lymphocytes of sarcomatoid RCCs. The genotype of EBV was determined as type 1. A few EBV-infected B cells expressed BZLF1 (an EBV immediate-early gene product) while none expressed EBNA-2 or latent membrane protein 1. This indicates that the B cells are of EBV latency type I, often replicating EBV. EBV infection did not affect the survival rates of patients with sarcomatoid RCC (P = 0.635, Kaplan-Meier analysis, log-rank test). CONCLUSION: EBV is present only in tumour-infiltrating B lymphocytes of sarcomatoid RCCs. The present study suggests that sarcomatoid RCC modulates a function of EBV-specific T cells controlling EBV replication, or stimulates differentiation of memory B cells into plasma cells.

Adult↗

PubMed2005

Occurrence of c-kit+ tumor cells in hepatitis B virus-associated hepatocellular carcinoma.

Progenitor cells, termed oval cells, are involved in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. By immunolabeling for c-kit and CD34 in human hepatitis B virus-associated cirrhosis with HCC (50 cases) and those with cirrhosis alone (10 cases), we found c-kit+ tumor cells in tumor tissue in 40 of 50 HCCs. The proportion was less than 0.1% of total tumor cell volume in most HCCs. Immunostaining for c-kit also was detected in sinusoidal endothelial cells in 43 of 50 HCCs. The incidence of oval cell occurrence in the adjacent nonneoplastic tissue in cases of HCC was high (44/50). The occurrence of oval cells, c-kit+ tumor cells, and c-kit+ sinusoidal cells in cases of human hepatitis B virus-associated HCC suggests that oval cell proliferation might be associated with the development of human hepatitis B virus-associated HCC. Furthermore, the c-kit+ sinusoidal cells might have a role in angiogenesis and progression of human hepatitis B virus-associated HCC.

Adult↗

PubMed2004

Cytokine-mediated induction of metallothionein in Hepa-1c1c7 cells by oleanolic acid.

Oleanolic acid (OA), a pentacyclic triterpene acid, has been reported to possess inducing activity of hepatic metallothionein (MT). However, the mechanism underlying its effects is unknown. This study investigated the effects of OA on the regulation of MT expression in an in vitro model. OA that was added directly to Hepa-1c1c7 cells had no effect on MT induction. However, MT and its mRNA levels increased markedly when the Hepa-1c1c7 cells were cultured with the OA-treated conditioned media from the RAW 264.7 cells. Co-treating the RAW 264.7 cells with OA and pentoxifylline, a TNF-alpha synthesis inhibitor, resulted in a decrease in the effects of OA on the MT induction. In the OA-exposed RAW 264.7 cell cultures, production and mRNA levels of TNF-alpha and IL-6 were increased. However, the MT induction activity was inhibited when antibodies to TNF-alpha and/or IL-6 were added to the OA-treated conditioned media from the RAW 264.7 cells. These results suggest that the up-regulation of MT expression by OA was mediated by the TNF-alpha and IL-6 released from UA-activated macrophages.

Animals↗

PubMed2004

Pretreatment with 1,8-cineole potentiates thioacetamide-induced hepatotoxicity and immunosuppression.

The effect of 1,8-cineole on cytochrome P450 (CYP) expression was investigated in male Sprague Dawley rats and female BALB/c mice. When rats were treated orally with 200, 400 and 800 mg/kg of 1,8-cineole for 3 consecutive days, the liver microsomal activities of benzyloxyresorufin- and pentoxyresorufin-omicron-dealkylases and erythromycin N-demethylase were dose-dependently induced. The Western immunoblotting analyses clearly indicated the induction of CYP 2B1/2 and CYP 3A1/2 proteins by 1,8-cineole. At the doses employed, 1,8-cineole did not cause toxicity, including hepatotoxicity. Subsequently, 1,8-cineole was applied to study the role of metabolic activation in thioacetamide-induced hepatotoxicity and/or immunotoxicity in animal models. To investigate a possible role of metabolic activation by CYP enzymes in thioacetamide-induced hepatotoxicity, rats were pre-treated with 800 mg/kg of 1 ,8-cineole for 3 days, followed by a single intraperitoneal treatment with 50 and 100 mg/kg of thioacetamide in saline. 24 h later, thioacetamide-induced hepatotoxicity was significantly potentiated by the pretreatment with 1,8-cineole. When female BALB/c mice were pretreated with 800 mg/kg of 1,8-cineole for 3 days, followed by a single intraperitoneal treatment with 100 mg/kg of thioacetamide, the antibody response to sheep red blood cells was significantly potentiated. In addition, the liver microsomal activities of CYP 2B enzymes were significantly induced by 1,8-cineole as in rats. Taken together, our results indicated that 1,8-cineole might be a useful CYP modulator in investigating the possible role of metabolic activation in chemical-induced hepatotoxicity and immunotoxicity.

Alanine Transaminase↗

PubMed2004

Suppression of CYP1A1 expression by naringenin in murine Hepa-1c1c7 cells.

Naringenin, dietary flavonoid, is antioxidant constituents of many citrus fruits. In the present study, we investigated the effect of naringenin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1A1 gene expression in mouse hepatoma Hepa-1c1c7 cells. Naringenin alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, the TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and naringenin in a dose dependent manner. TCDD-induced CYP1A1 mRNA level was also markedly suppressed by naringenin. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and electrophoretic mobility shift assay revealed that naringenin reduced transformation of the aryl hydrocarbons receptor(AhR) to a form capable of specifically binding to the DRE sequence in the promoter of the CYP1A1 gene. These results suggest the down regulation of the CYP1A1 gene expression by either naringenin in Hepa-1c1c7 cells might be antagonism of the DRE binding potential of nuclear AhR.

Animals↗

PubMed2004

A distinct expression pattern and point mutation of c-kit in papillary renal cell carcinomas.

KIT is expressed not only in tumors derived from hematopoietic stem cells, melanocytes, germ cells, mast cells, and interstitial cells of Cajal, but also in other malignancies such as chromophobe renal cell carcinoma. This pattern of KIT expression prompted us to investigate the expression and mutation of c-kit gene exons 9, 11, 13, 17, and intron 17 in the different subtypes of renal cell carcinomas (n=66) and non-neoplastic kidneys (n=12). We found that KIT showed strong immunoreactivity in the cytoplasm of papillary renal cell carcinomas (100%), but on the cell membranes of chromophobe renal cell carcinomas (100%). Interestingly, a specific point mutation of the c-kit intron 17 (T->A) was found only in papillary renal cell carcinomas (94%). Our study demonstrates that the expression pattern and one mutation of c-kit may distinguish papillary renal cell carcinomas.

Base Sequence↗