Biomedical subjects

Hyun-Chul Lee

Publications and source records attributed to Hyun-Chul Lee.

At least 19 recordsLinked to original sources

PubMed2006

Development of ligand-dependent regulatory system and its application to gene therapy of insulin-dependent diabetes mellitus.

To develop an inducible expression system, the enhanced artificial nuclear receptors and target reporters were constructed. Artificial nuclear receptors were generated by fusing three domains, consisting of DNA-binding domain (DBD) of GAL4, ligand binding domain (LBD) of progesterone or estrogen receptor, and activation domain (AD) of VP16, sterol regulatory element binding protein (SREBP)-1a, or SREBP-2. The activation domain of SREBP-1a showed most potent transcriptional activity. The maximal level of target reporter gene expression was extremely elevated by the usage of ATP citrate-lyase (ACL) minimal promoter -60/+67 in place of artificial TATA promoter, while the SV40 enhancer severely increased the basal transcription in the absence of ligand. The induction system, developed in the present study, was applied to cell therapy, resulting in successful induction of single-chain insulin analogue (SIA) gene expression to correct the hyperglycemia in diabetic animals. By means of subcutaneous cell therapy, the SIA gene expression rapidly occurred after the local topical application of ligand. These results suggest that our system represents a powerful tool for transcriptional regulation of target gene that can be used for diverse applications, ranging from basic research to gene therapy.

Animals↗

PubMed2006

Adriamycin release from self-assembling nanospheres of poly(DL-lactide-co-glycolide)-grafted pullulan.

Poly(DL-lactide-co-glycolide)-graft pullulan (PuLG) was synthesized to produce a hydrophobically modified polysaccharide. Specific pullulan and poly(DL-lactide-co-glycolide) (PLGA) (abbreviated as PuLG) appeared in the peaks of the PuLG spectra on (1)H NMR spectroscopy, suggesting that PLGA was successively grafted to the pullulan backbone. PuLG nanospheres have a round shape with a particle size of about 75-150 nm. From the fluorescence excitation spectra in a fluorescence probe study, the critical association concentration (CAC) values were determined to be 0.017 g/l for PuLG-1, 0.0054 g/l for PuLG-2, and 0.0047 g/l for PuLG-3. The drug contents of the PuLG nanospheres were approximately 20-30% (w/w). As the drug contents of PuLG nanospheres increased, the drug release rate from nanospheres decreased. The drug release rate from PuLG nanospheres was delayed as the molecular weight of PuLG increased. PuLG copolymer with higher graft ratio of PLGA showed slower degradation rate rather than that with lower graft ratio. Since degradation rate of PuLG was taken over 1 month, drug release was governed by diffusion mechanism rather than degradation mechanism.

Antibiotics, Antineoplastic↗

PubMed2006

The relation between birth weight and insulin resistance in Korean adolescents.

Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-beta, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-beta were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight.

Adolescent↗

PubMed2006

Enhancement of cytokine-mediated NF-kappaB activation by phosphatidylinositol 3-kinase inhibitors in monocytic cells.

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays crucial roles in inflammation and immunity. Understanding the positive and negative regulation of NF-kappaB activity is therefore of fundamental importance. A few previous studies reported that inhibition of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway enhances lipopolysaccharide (LPS)-induced activation of NF-kappaB. However, many aspects of the PI3K negative regulation of NF-kappaB activation remain to be clarified. The present study was conducted to shed light on cell-type specificity, stimulus specificity, and upstream mechanisms of the enhanced NF-kappaB activation by PI3K inhibitors. Gel shift assays showed that LY294002 (LY29) potently increased interleukin (IL)-1-induced NF-kappaB DNA binding in human monocytic THP-1 cells. Moreover, another PI3K inhibitor 3-methyladenine also strongly enhanced IL-1-induced NF-kappaB DNA binding, while LY303511, an inactive analogue of LY29, did not increase the NF-kappaB DNA binding. Compared with LY29, wortmannin (WM) effected only a marginal enhancement of NF-kappaB DNA binding. LY29 treatment also augmented tumor necrosis factor (TNF)-mediated NF-kappaB DNA binding. Furthermore, LY29, but not WM, increased cyclooxygenase (COX)-2 mRNA expression by IL-1 or TNF in THP-1 cells. Likewise, prostaglandin E2 production by IL-1 was increased by LY29, but not by WM. Western blot analysis demonstrated that IkappaB kinase (IKK) activation as well as IkappaB-alpha degradation and NF-kappaB nuclear translocation was elevated by LY29 and WM. Among the tested cell lines (HL-60, ECV304, Hep-2, and Molt-4), only HL-60, a promyelocytic cell line, showed enhanced NF-kappaB DNA binding by LY29. These results suggest that pharmacological inhibition of PI3K enhances the NF-kappaB-activating pathways by IL-1 through augmentation of IKK activation in myeloid/monocytic cells and the NF-kappaB enhancement is more robustly achieved by LY29 than by WM.

Active Transport, Cell Nucleus↗

PubMed2006

Preparation of semi-interpenetrating polymer networks composed of chitosan and poloxamer.

Through semi-interpenetration of polymer networks with poloxamer, mechanical properties of chitosan (CS) sponge were increased for wound dressing application. Synthesis of poloxamer macromer was confirmed by proton nuclear magnetic resonance (1H NMR) spectra. Possible interactions between CS and poloxamer in semi-interpenetrating polymer networks (SIPNs), and changes in crystalline structures of both polymers were evaluated by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), respectively. Swelling behavior, thermal analysis, mechanical properties, and morphology of SIPNs were studied by thermal gravimetric analysis, differential scanning calorimetry (DSC), compressive modulus measurement, and scanning electron microscopy (SEM), respectively. Preparation of poloxamer macromer, and intermolecular hydrogen bonding between CS and poloxamer were confirmed by NMR and FTIR, respectively. Melting temperature of poloxamer in SIPNs decreased due to prevention of crystallization by incorporation of CS. Formation of SIPNs with poloxamer and increasing poloxamer content in CS/poloxamer SIPNs increased mechanical strength of CS sponge compared with CS/poloxamer blend. Formation of SIPNs with poloxamer remarkably increased water content of CS due to hydrophilicity of CS and poloxamer. These results suggest CS/poloxamer sponges prepared by SIPNs method have good possibility for wound dressing application owing to rapid water adsorption, high mechanical strength, and interconnected cross-sectional morphology of SIPNs.

Adsorption↗

PubMed2006

Inhibitory effect of Weissella cibaria isolates on the production of volatile sulphur compounds.

AIMS: The objective of this study was to characterize the inhibitory effects of Weissella cibaria isolates on volatile sulphur compounds (VSC) production both in vitro and in vivo. MATERIAL AND METHODS: We isolated and identified three hydrogen peroxide-generating lactobacilli from children's saliva, and assessed their inhibitory effects on VSC production and Fusobacterium nucleatum proliferation. Clinical studies were conducted with 46 subjects in order to measure the VSC of their mouth air. RESULTS: These lactobacilli were identified as W. cibaria. These isolates inhibited the production of VSC by F. nucleatum (p<0.05). The concentration of F. nucleatum was decreased by 5-log cycles as a result of exposure to the W. cibaria strains (p<0.05), whereas the catalase-treated W. cibaria cultures exerted no evident inhibitory effects on F. nucleatum replication. In the clinical studies, gargling with one isolate resulted in a significant reduction in the levels of H2S and CH3SH by approximately 48.2% (p<0.01) and 59.4% (p<0.05), respectively. CONCLUSIONS: These results indicate that W. cibaria isolates possess the ability to inhibit VSC production under both in vitro and in vivo conditions, demonstrating that they bear the potential for development into novel probiotics for use in the oral cavity.

Adult↗

PubMed2005

Immune response induced by Salmonella typhimurium defective in ppGpp synthesis.

Systemic infection by Salmonella typhimurium requires coordinated expression of virulence genes found primarily in Salmonella Pathogenecity Islands (SPIs). We have previously reported that the intracellular signal that induces these virulence genes is a stringent signal molecule, ppGpp [Song et al. J Biol Chem 2003;279:34183]. In this study, we found that relA and spoT double mutant Salmonella (DeltappGpp strain), which is defective in ppGpp synthesis, was virtually avirulent in BALB/c mice. Subsequently, the live vaccine potential of the avirulent DeltappGpp Salmonella strain was determined. A single immunization with live DeltappGpp Salmonella efficiently protected mice from challenge with wild-type Salmonella at a dose 10(6)-fold above the LD50 30 days after immunization. Various assays revealed that immunization of mice with the DeltappGpp strain elicited both systemic and mucosal antibody responses, in addition to cell-mediated immunity.

Animals↗

PubMed2005

Severity of ultrasonographic liver steatosis and metabolic syndrome in Korean men and women.

AIM: To evaluate the association between the severity of liver steatosis and metabolic syndrome in apparently healthy Korean adults. METHODS: We examined 1 022 men and women, aged 30-79 years, who participated in a health screening test. A standard interview, anthropometrics, biochemical studies, and abdominal ultrasonography were conducted for each participant. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III, with a modification for the waist circumference cut-off level. The severity of liver steatosis was evaluated using liver ultrasonography, and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (gamma-GT) levels were determined. RESULTS: Ultrasonographic liver steatosis was strongly associated with metabolic syndrome and common metabolic abnormalities. Compared with people without steatosis, people with mild, moderate, and severe steatosis had adjusted odds ratios for metabolic syndrome of 1.72 (95%CI, 1.01-2.94), 2.89 (1.75-4.76) and 3.53 (1.25-9.98) in men, and 2.86 (1.64-5.01), 3.19 (1.80-5.65) and 3.70 (0.82-16.73) in women, respectively. The serum AST level was not associated with metabolic syndrome. The serum ALT and gamma-GT levels were significantly associated with metabolic syndrome in men but not in women. CONCLUSION: The occurrence of metabolic syndrome shows a stronger association with the severity of ultrasonographic steatosis than with the serum liver enzyme levels. The degree of fatty infiltration detected on ultrasonography can be used as an indicator of liver dysfunction attributable to metabolic abnormalities.

Adult↗

PubMed2005

Characteristics of type 2 diabetes in terms of insulin resistance in Korea.

The aim of this study was to assess the implications of insulin resistance on the clinical and biochemical profiles of Korean type 2 diabetic patients. 122 patients with type 2 diabetes underwent a short insulin tolerance test to assess insulin resistance. Subjects were classified in tertiles according to ISI (insulin sensitivity index), and the tertile I (the insulin- resistant group) and tertile III (the insulin-sensitive group) clinical and biochemical parameters were compared. Age, waist circumference (WC), systolic blood pressure (SBP), HbA1c, body fat content, and fasting plasma glucose were significantly higher in tertile I than tertile III (all p < 0.05). The frequency of hypertension and family history of cerebrovascular disease (CVD) were greater in tertile I than III (p < 0.05). To evaluate the factors affecting ISI, multiple regression was performed, and age, WC, SBP, HbA1c, and body fat content were found to be independently related to insulin resistance (p < 0.05). Old age, hypertension, central obesity, and poor glycemic control were identified as clinical parameters of insulin resistance in Korean type 2 diabetic patients.

Adult↗

PubMed2005

Cellular recognition of paclitaxel-loaded polymeric nanoparticles composed of poly(gamma-benzyl L-glutamate) and poly(ethylene glycol) diblock copolymer endcapped with galactose moiety.

Poly(gamma-benzyl L-glutamate) (PBLG)/poly(ethylene glycol) (PEG) diblock copolymer endcapped with galactose moiety (abbreviated as GEG) was synthesized and characterized for study of liver-specific targeting. From dynamic light scattering measurement, particle sizes of copolymeric nanoparticles were decreased with an increase of PEG in the copolymer. The morphology of GEG-3 nanoparticles observed by transmission electron micrograph was observed as almost spherical shapes and ranged about 50-300 nm. From the structural characterization using 1H nuclear magnetic resonance, both characteristic peaks of PBLG and PEG were visible in CDCl3 but the characteristic peaks of PBLG were invisible in D2O, indicating that GEG block copolymers are found to the core-shell type nanoparticles in water with PBLG innercore and PEG outershell, exposing that galactose moiety of GEG block copolymers are outerwards oriented on the nanoparticle surfaces. By galactose-specific aggregation test of particles using beta-galactose specific lectin, and flow cytometry measurement, specific interaction between asialoglycoprotein receptors (ASGPR) of HepG2, human hepatoma cell line, and galactose moieties of the GEG nanoparticles was confirmed. From cell cytotoxicity test, HepG2 cells with ASGPR are more sensitive to paclitaxel (TX)-loaded nanoparticles than free TX whereas, P388 cells, murine leukemia cell line, and SK-Hep 01, human hepatoma cell line, without ASGPR is less sensitive to TX-loaded nanoparticles than free TX, suggesting that specific interaction between HepG2 cells and galactose moiety of the nanoparticles occurred.

Animals↗

PubMed2005

Strain-dependent suppressive effects of BCG vaccination on asthmatic reactions in BALB/c mice.

BACKGROUND: The choice of BCG vaccine strain may play an important role in vaccination efficiency. OBJECTIVE: To investigate whether the suppressive effects of BCG on asthma depend on the strain of BCG. METHODS: Female BALB/c mice were injected intraperitoneally with 1 of 4 different strains of BCG (1 X 10(6) CFU): Pasteur F1173P2, Tokyo 172, Tice, and Connaught. Seven days later, the animals were sensitized by 2 injections of ovalbumin (20 microg) at 2-week intervals before being provoked with 1% ovalbumin aerosols on 3 successive days. Thereafter, the mice underwent a methacholine bronchial challenge and were killed to quantify the inflammatory cells and cytokines in bronchoalveolar lavage fluid and the supernatant of cultured splenocytes. RESULTS: The eosinophil proportion in the bronchoalveolar lavage fluid was significantly lower and the concentration of interferon-gamma and the interferon-gamma-interleukin 5 (IL-5) ratio in the supernatant of cultured splenocytes were significantly higher in each of the BCG-treated groups (n=10 per group) than in the asthma control group (n=15). However, the methacholine sensitivity (P < .05) and IL-5 concentration (P < .01) in the supernatant of cultured splenocytes were significantly lower only in the group treated with the Tokyo strain of BCG. There was a significant positive correlation between IL-5 and IL-10 concentrations (r = 0.79; P < .001). CONCLUSIONS: The 4 strains of BCG suppressed asthma to different degrees, but all strains induced a shift in the T(H)1/T(H)2 balance toward T(H)1 without increasing IL-10-related regulatory T-cell activity.

Animals↗

PubMed2005

O-palmitoylcurdlan sulfate (OPCurS)-coated liposomes for oral drug delivery.

O-Palmitoylcurdlan sulfate (OPCurS) was applied to the liposomal surface to improve the stability of liposomes. To synthesize OPCurS, curdlan was chemically sulfated and then modified with a palmitoyl derivative. The synthesized OPCurS was characterized by Fourier transform-infrared spectroscopy (FT-IR). OPCurS-coated liposomes prepared by the solvent evaporation method were characterized for size, shape, surface charge, and stability in simulated gastric fluid (SGF) and sodium cholate solution. The sizes of OPCurS-coated liposomes increased with the OPCurS content of liposomes and zeta potential decreased when OPCurS was applied to the liposomal surface. With the increase in the content of OPCurS attached to the liposomal surface, the stability of liposomes in SGF and sodium cholate solution was gradually induced and the stability was most improved at a lipid/OPCurS weight ratio of 1.5. Liposomes not coated with OPCurS released 99.5+/-2.3% of the initial 5-carboxyfluorescein (5-CF) content, whereas OPCurS-coated liposomes released 53.7+/-3.7%. OPCurS on the surface of liposomes suppressed the release of 5-CF. Theses results indicate that OPCurS-coated liposomes can be effectively used as a drug delivery carrier via oral administration.

Administration, Oral↗

PubMed2004

Graves' disease associated with Klinefelter's syndrome.

Klinefelter's syndrome is one of the most common forms of primary hypogonadism and infertility in males. It is characterized by small and firm testes, gynecomastia, azoospermia, and an elevated gonadotropin level. The frequencies of diabetes mellitus, breast cancer, and germ cell neoplasia increases in Klinefelter's syndrome. We report upon a 35 year-old male patient with Graves' disease in association with Klinefelter's syndrome; as confirmed by chromosome analysis. The patient is being treated with antithyroid medication for Graves' disease and by testosterone replacement for Klinefelter's syndrome.

Adult↗

PubMed2004

LY294002 inhibits monocyte chemoattractant protein-1 expression through a phosphatidylinositol 3-kinase-independent mechanism.

The effects of LY294002 (LY29) and wortmannin (WM), inhibitors of phosphatidylinositol 3-kinase (PI3K), on monocyte chemoattractant protein-1 (MCP-1) expression by human umbilical vein endothelial cells were investigated. Complete inhibition of interleukin (IL)-1beta-induced Akt phosphorylation occurred at 50 microM LY29 or 100 nM WM. At these concentrations, LY29, but not WM, significantly inhibited constitutive and IL-1beta-induced MCP-1 expression at both protein and mRNA levels. LY303511 (LY30), an inactive analogue of LY29, also inhibited MCP-1 expression. LY29 and LY30 inhibited activation of nuclear factor-kappaB (NF-kappaB). These results suggest that LY29 inhibits MCP-1 expression at least in part via suppression of NF-kappaB, independent of PI3K, and the structure of LY29 and LY30 may be a novel template for development of new anti-inflammatory drugs.

Androstadienes↗

PubMed2004

Preparation of semi-interpenetrating polymer networks composed of silk fibroin and poloxamer macromer.

A system was designed to utilize silk fibroin (SF) as a matrix for wound dressing. For this system, we prepared a sponge type of porous semi-interpenetrating networks (SIPNs) hydrogel composed of SF and poloxamer 407 macromer to enhance the mechanical and functional properties of SF. The thermal and mechanical properties of the hydrogels as well as their swelling behaviors were studied by means of differential scanning calorimetry, compressive modulus measurement, and gravimetric method, respectively. The morphology and crystalline structure of these SIPN hydrogels were also investigated by scanning electron microscopy (SEM) and wide-angle diffractometry, respectively. Conformational change of SF from random coil to beta-sheet structure was accelerated by formation of SIPNs with poloxamer. The melting temperature of poloxamer in the SIPNs decreased due to the prevention of crystallization by the incorporation of SF. The mechanical strength of SIPNs hydrogel was much higher than those of SF itself or SF/poloxamer blend and increased with the poloxamer content. The equilibrium water content of SF was remarkably increased by formation of SIPNs with poloxamer due to the hydrophilicity of poloxamer. The crystallinity and morphology of SIPNs hydrogel were affected by SIPNs hydrogel composition.

Biological Dressings↗

PubMed2004

Generation of cytotoxic donor CD8+ T cells against relapsing leukemic cells following allogeneic transplantation by stimulation with leukemic cell- or leukemic lysate pulsed donor cell-derived dendritic cells.

To treat leukemia relapse after allogeneic hematopoietic stem cell transplantation (HSCT), we investigated the possibility of immunotherapy using donor CD8+ T cells that were generated by stimulating leukemic cell-derived dendritic cells (leukemic-DCs) or leukemic cell lysate pulsed donor cell-derived DCs (donor-DCs). Leukemic- and donor-DCs were generated from mononuclear cells of patients and CD14+ cells of HLA-matched donors, respectively. The expression of CD80, CD83, CD86, CD1a, and CD40 on leukemic-DCs was significantly lower than that on donor-DCs. Donor-DCs exhibited a higher capacity to stimulate allogeneic T cells compared with leukemic-DCs. Donor CD8+ T cells stimulated by leukemic- or donor-DCs were more cytotoxic than unprimed CD8+ T cells, and slightly higher cytotoxicity was observed with donor-DCs compared to leukemic-DCs. This study indicates that leukemic- or donor-DCs pulsed with leukemic cell lysates can effectively prime donor cytotoxic T cells in vitro, and that they may be used as a potential alternative tool for treating leukemic patients who relapse after allogeneic HSCT.

CD8-Positive T-Lymphocytes↗

PubMed2004

Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes.

OBJECTIVE: Despite the popularity of coronary stenting in coronary artery disease (CAD), restenosis remains a challenging clinical problem. This study evaluated the efficacy of rosiglitazone for preventing in-stent restenosis in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a prospective, randomized, case-controlled trial involving 95 diabetic patients with CAD who were randomly assigned to either the control or rosiglitazone group (48 and 47 patients, respectively). Quantitative coronary angiography (QCA) was performed at study entry and again at 6-month follow-up. The primary end point was the restenosis rate, which was determined by QCA. RESULTS: Eighty-three patients (45 patients with 55 lesions in the control group and 38 patients with 51 lesions in the rosiglitazone group) completed follow-up angiography. Rosiglitazone treatment for 6 months reduced fasting insulin concentration. The high-sensitivity C-reactive protein concentration was significantly reduced in the rosiglitazone group compared with that in the control group (from 2.92 +/- 1.98 to 0.62 +/- 0.44 mg/l, P < 0.001 vs. from 2.01 +/- 1.33 to 1.79 +/- 1.22 mg/l, P = NS). However, the baseline and follow-up glucose and lipid concentrations were not different between two groups. The rate of in-stent restenosis was significantly reduced in the rosiglitazone group compared with the control group (for stent lesions: 17.6 vs. 38.2%, P = 0.030). The rosiglitazone group had a significantly lower degree of diameter stenosis (23.0 +/- 23.4% vs. 40.9 +/- 31.9%, P = 0.004) compared with the control group. CONCLUSIONS: We demonstrated that treatment with rosiglitazone significantly reduces in-stent restenosis in diabetic patients with CAD who underwent coronary stent implantation.

Adult↗

PubMed2003

Development and validation of a computerized exercise intervention program for patients with type 2 diabetes mellitus in Korea.

This study was designed to develop and validate a computerized exercise intervention program using the transtheoretical model (TTM) for Korean patients with type 2 diabetes mellitus (DM). This computerized program was web-based and developed by designing a flow chart. An expert group (n=24), who validated the content of the computerized program, produced a mean score for the evaluation scale of 4.25 (SD.56). Of the patients (n=28) with type 2 DM who participated in clinical validity testing of the program, the mean score for the satisfaction scale was 4.82 (SD.12). In the validation of the program, significant differences between baseline and after-intervention were observed in the stage of readiness for exercise (Z=-3.78, p < 0.001), physical activity (Z=-2.33, p < 0.05), blood glucose profiles [FBS (Z=-2.84, p < 0.01), pc 2 hr. glucose (Z=-2.33, p < 0.05), HbA1c (Z=-2.77, p < 0.01)], and VO2max (Z=-2.52, p < 0.01). The study confirmed that the computerized program could be used to construct a database and continue to provide follow-up intervention for patients in all stages.

Diabetes Mellitus, Type 2↗