Biomedical subjects

Y K Sung

Publications and source records attributed to Y K Sung.

15 recordsLinked to original sources

PubMed2005

Catalase and PPARgamma2 genotype and risk of systemic lupus erythematosus in Koreans.

Catalase (CAT) and peroxisome proliferator activated receptor-gamma2 (PPARgamma2) are important regulators of oxidative stress and inflammation, which may contribute to the development of systemic lupus erythematosus (SLE). The objective of this study was to investigate the effects of genetic polymorphisms of CAT and PPARy2 on risk and severity of SLE in a Korean population. DNA was isolated from blood samples collected from 345 patients with SLE and 400 controls. Genotyping for the -262C-->T polymorphism of CAT and the Pro 12Ala polymorphism of PPARgamma2 were performed by PCR-RFLP analysis. The severity of SLE was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). No association was observed between genotypes for any of the clinical manifestations of SLE. CAT and PPARgamma2 genotypes were not associated with either risk or severity of SLE. For subjects who were carriers of the high activity T allele for CAT and have the Pro/Pro genotype for PPARgamma2, the odds ratio (95% confidence interval) for risk of SLE was 0.45 (0.23-1.08). Our results suggest that genetic polymorphisms of CAT and PPARy2 do not play a significant role in the development of SLE in a Korean population. A possible protective effect of a combined genotype warrants further investigation.

Adult↗

PubMed2000

Development of biomaterials for gene therapy.

Novel biocompatible polymeric gene carriers have been examined for their potential in treating various genetic and acquired diseases. The use of polymeric gene carriers may overcome the current problems associated with viral vectors in safety, immunogenicity, and mutagenesis. However, effective polymer-based gene therapy requires the control of cellular access and uptake, intracellular trafficking, and nuclear retention of plasmid DNA. Inefficient endosomal release, cytoplasmic transport, and nuclear entry of plasmids are currently limiting factors in the use of polymers for effective plasmid-based gene therapy. Therefore, several different polymeric gene carriers have been designed recently in an attempt to overcome these problems. This review explores the conceptual and experimental aspects of polymer-based gene delivery and presents an overview on the recent use of polymers to enhance the effectiveness of plasmid-based systems. Despite their current limitations, polymeric carriers have significant potential as commercially viable gene medicines.

Biocompatible Materials↗

PubMed2000

beta-Chitin-based wound dressing containing silver sulfurdiazine.

Physical and biological properties of some wound dressing materials based on beta-chitin were studied. Water vapor transmission rates (WVTR), oxygen permeabilities and biodegradation kinetics were examined for film-type samples. WVTR of samples was in the range 2400-2800 g/m2/day. However, oxygen permeabilities of the samples were relatively low. To improve oxygen permeabilities, porous sponge-type wound dressing materials were prepared. In addition, these sponge-type samples contained antimicrobial agents, silver sulfadiazine (AgSD), in order to prevent bacteria infection on a wound surface. Anti-microbacterial tests on agar plate were carried out to confirm the bactericidal capacity of present materials. These materials impregnating AgSD had the complete bactericidal capacity against pseudomonas aeruginosa up to 7 days. Finally, a wound healing effect of beta-chitin-based semi-interpenetrating polymer networks was evaluated from the animal test using the wistar rat in vivo. Histological studies confirm the proliferation of fibroblasts in the wound bed and a distinct reduction in infectious cells.

Journal Article↗

PubMed1999

Odorants induce the phosphorylation of the cAMP response element binding protein in olfactory receptor neurons.

Although odorants are known to activate olfactory receptor neurons through cAMP, the long-term effects of odorant detection are not known. Our recent findings indicate that there is also a delayed and sustained cAMP response, with kinetics sufficient to mediate long-term cellular responses. This cAMP response is mediated by cGMP through activation of adenylyl cyclase by protein kinase G (PKG). Therefore, we investigated the ability of odorants to regulate gene expression in rat olfactory epithelium. The cAMP-responsive binding protein (CREB) is a well-characterized transcription factor regulated by cAMP. We examined CREB activity in rat olfactory epithelium and olfactory receptor neurons (ORNs) after stimulation with odorants. Odorants increased levels of phosphorylated CREB in olfactory epithelium in vivo, and this increase was localized to ORNs in vitro. Incubation with 8-bromo-cGMP or sodium nitroprusside, a guanylyl cyclase activator, also increased phosphorylated CREB. In vitro, cAMP-dependent protein kinase phosphorylated CREB. In contrast, PKG failed to phosphorylate CREB directly in vitro. Our results demonstrate that the delayed odorant-induced cAMP signal activates CREB, which in turn may modulate gene expression in ORNs. In addition, cGMP indirectly affects CREB activation. This effect of cGMP on CREB activity through cAMP provides another mechanism for the modulation of CREB.

Animals↗

PubMed1998

Clonazepam release from core-shell type nanoparticles in vitro.

Block copolymers consisting of poly(gamma-benzyl L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene oxide) (PEO) as the hydrophilic block were synthesized and characterized. Core-shell type nanoparticles of the block copolymers (abbreviated as GE) were prepared by the diafiltration method. The particle size diameter obtained by dynamic light scattering of GE-1 (PBLG content: 60.5 mol%), GE-2 (PBLG content: 40.0 mol %), GE-3 (PBLG content: 124.4 mol %) copolymer was 309.9 +/- 160.9, 251.9 +/- 220.6 and 200.5 +/- 177.1nm, respectively. The shape of the nanoparticles by SEM or TEM was almost spherical. The critical micelle concentration of the block copolymers obtained by fluorescence spectroscopy was dependent on the chain length of hydrophobic PBLG. The micelle structure of the copolymers nanoparticle was very stable against sodium dodecyl sulfate. Clonazepam (CZ) was loaded onto the core part of the nanoparticle as the crystalline state. Release of CZ from the nanoparticles in vitro was dependent on the drug loading contents and PBLG chain length.

Anticonvulsants↗

PubMed1998

Methoxy poly(ethylene glycol) and epsilon-caprolactone amphiphilic block copolymeric micelle containing indomethacin. II. Micelle formation and drug release behaviours.

Amphiphilic diblock copolymer composed of methoxy poly(ethylene glycol) and epsilon-caprolactone (epsilon-CL) was prepared by polymerization of epsilon-CL initiated with MePEG. MePEG/epsilon-CL block copolymeric micelles containing indomethacin (IMC) were prepared by a dialysis method and evaluated as a novel drug carrier. The size of micelle formed was less than 200 nm, and the size distribution of the micelle showed a narrow and monodisperse unimodal pattern. Also, the micelles formed by a dialysis method exhibited spherical structures. The indomethacin content in nanospheres was about 42.2%, for those prepared using copolymer, having molecular weight of about 12,000 and polymer/IMC weight ratio of 1/1. A release rate of indomethacin from nanospheres was slow, and thus the release continued over 15 days. As the molecular weights of the copolymer and the amount of drug entrapped increased, the release rate decreased. These results indicated that the drug-loaded nanospheres could be useful as a novel drug carrier in injectable delivery systems for hydrophobic drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Methoxy poly(ethylene glycol)/epsilon-caprolactone amphiphilic block copolymeric micelle containing indomethacin. I. Preparation and characterization.

Amphiphilic diblock copolymers composed of methoxy polyethylene glycol (MePEG) and epsilon-caprolactone (epsilon-CL) were prepared for the formation of micelles. The copolymer was formed by ring opening mechanism of epsilon-CL in the presence of MePEG containing hydroxyl functional groups at one end of the chain. To estimate their feasibility as vehicles for drugs, MePEG/epsilon-CL block copolymeric micelles were prepared by dialysis against water. Indomethacin was incorporated into the hydrophobic inner core of these micelles as a typical model drug for non-steroidal anti-inflammatory drugs. From the dynamic light scattering measurements, the size of micelle formed was less than 200 mm, and their size increases with the amount of indomethacin encapsulated into the inner core of MePEG/epsilon-CL block copolymers. The selected solvents used to prepare micelles by dialysis in water affect the size of polymeric micelles. As the hydrophobic components of copolymer increase, the critical micelle concentration values and hydrophilic-lipophilic balance decreased. An increase of molecular weight and hydrophobic components of diblock copolymer produced larger micelles.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

In vitro blood compatibility of functional group-grafted and heparin-immobilized polyurethanes prepared by plasma glow discharge.

Blood compatibilities of functional group-grafted and heparin-immobilized polyurethanes (PUs) were investigated using in vitro thrombus formation, plasma recalcification time (PRT), activated partial thromboplastin time (APTT), platelet adhesion and activation, and peripheral blood mononuclear cell (PBMC) activation. In the experiment with plasma proteins, PRT was shortened on amine group-grafted PU (PU-NH2) but prolonged on heparin-immobilized polyurethane (PU-Hep) when compared to PU control. APTT was significantly prolonged on PU-Hep, suggesting the binding of immobilized heparin to antithrombin III. The percentage of platelet adhesion was slightly increased by the introduction of functional groups such as carboxylic acid and primary amine on PU surfaces, but significantly decreased by the immobilization of heparin on the same substrate. The percentage of serotonin released from platelets adhered on surface-modified PUs was increased with increase of platelet adhesion. In the PBMC experiment, cells adhered less on heparin-immobilized PUs than on functional group-grafted PUs, and the production levels of tumour necrosis factor mRNAs from the cells stimulated by heparin-immobilized PU (PU-N-Hep) were smaller than those by the other substrates.

Amines↗

PubMed1996

Potato yellow mosaic geminivirus AC2 protein is a sequence non-specific DNA binding protein.

The AC2 protein of potato yellow mosaic geminivirus (PYMV) is by analogy with related geminiviruses thought to be a transcriptional activator protein. We have over-expressed the AC2 open reading frame in E. coli and purified the protein from bacterial extracts to near homogeneity. We have studied the interaction of the AC2 protein with DNA and from gel retardation assays shown that it binds both double-stranded (ds) and single-stranded (ss) DNA non-specifically. The binding to PYMV intergenic region ds DNA appeared to be independent of the presence of zinc ions and did not require the protein to be phosphorylated.

Base Sequence↗

PubMed1996

Preparation and surface characterization of functional group-grafted and heparin-immobilized polyurethanes by plasma glow discharge.

Functional group-grafted polyurethanes were prepared by oxygen plasma discharge treatment, followed by graft polymerization of 1-acryloylbenzotriazole (AB) and a subsequent substitution reaction of AB with sodium hydroxide and ethylene diamine. The primary amine or carboxylic acid groups grafted on the surfaces were coupled with heparin using water-soluble carbodiimide. The modified surfaces were characterized by measuring the water contact angle, electron spectroscopy for chemical analysis and attenuated total reflection Fourier-transform infrared spectroscopy. The amount of heparin covalently immobilized on the primary amine- and carboxylic acid group-grafted polyurethanes were 2.0 and 1.4 micrograms cm-2, respectively, as determined by the toluidine blue method. The water contact angle of the polyurethanes was decreased by AB grafting, and further decreased by the introduction of functional groups such as carboxylic acid and primary amine and immobilization of heparin, showing increased hydrophilicity of the modified surfaces. Heparin was almost not released from the immobilized surfaces in the physiological solution for 100 h, indicating good stability of immobilized heparin.

Amines↗

PubMed1995

Pseudorecombination and complementation between potato yellow mosaic geminivirus and tomato golden mosaic geminivirus.

Pseudorecombinants made by exchanging the cloned, infectious genome components (DNAs A and B) of potato yellow mosaic geminivirus (PYMV) and the common strain (cs) of tomato golden mosaic geminivirus (csTGMV) are not infectious in their common host Nicotiana benthamiana. In an N. benthamiana leaf disc assay neither PYMV DNA A nor TGMV DNA A transreplicated each other's DNA B component. The ability of PYMV and TGMV to mediate the systemic movement of each other's DNA A was investigated following coinoculation of N. benthamiana with both genome components of one virus (the helper virus) and DNA A of the other virus (the dependent virus). Movement of the dependent virus DNA A in both cases illustrates interchangeability between the DNA B-encoded movement proteins of New World geminiviruses which infect solanaceous hosts. We have studied this genetic interchangeability further in separate co-agroinoculation experiments with N. benthamiana plants using TGMV DNA A to complement mutations in PYMV open reading frame (ORF) AC2, which encodes a protein that trans-activates the expression of virion sense promoters, and in PYMV ORF AC3, which specifies a protein that enhances viral DNA replication. TGMV DNA A complemented a PYMV AC2 mutant and restored its infectivity and it also complemented a PYMV AC3 mutant and restored the reduced DNA phenotype.

Base Sequence↗

PubMed1995

Mutational analysis of potato yellow mosaic geminivirus.

Mutations have been inserted into the virion and complementary sense ORFs encoding proteins with M(r)s in excess of 9 kDa of both DNA A and DNA B of potato yellow mosaic geminivirus (PYMV). Wild-type and mutant monomeric clones were tested for their ability to replicate, produce PYMV-specific DNA, spread and cause symptoms in Nicotiana benthamiana plants following biolistic inoculation. Dimeric clones of the DNA A mutants were also investigated by agroinoculation of leaf discs. In contrast to N. benthamiana plants agroinoculated with PYMV DNA A, in which the wild-type DNA A component was capable of limited independent replication and spread, both excised DNA A and B components were required for DNA replication and symptom development in plants inoculated by the biolistic method. Mixtures of both genomic components were also infectious for potato plants following biolistic inoculation. Mutations in ORFs AL1, AL2, BR1 and BL1 resulted in clones incapable of infecting N. benthamiana plants. However, the AL2 mutation, but not the AL1 mutation, allowed viral DNA replication in leaf discs. Mutations to both the AR1 and AL3 ORFs produced clones which were infectious in plants but showed a considerable delay in the production of attenuated symptoms as compared to wild-type infections. Mutating the AL3 ORF dramatically reduced viral DNA replication in both whole plants and leaf discs. Mutations to the AL4 ORF produced clones which were as infectious for both N. benthamiana and potato plants as the wild-type clones. Our results are compared with those from mutagenesis studies on related bipartite geminiviruses.

Cloning, Molecular↗

PubMed1994

The infectivity of dimeric potato yellow mosaic geminivirus clones in different hosts.

Head-to-tail dimeric clones of both DNA A and DNA B of potato yellow mosaic geminivirus (PYMV) were constructed. These constructs were infectious when inoculated onto Nicotiana benthamiana plants either as DNA or by agroinoculation and were also infectious for tomato plants by agroinoculation. The dimers were not infectious for potato plants following inoculation by either method. Symptom induction required both DNA A and DNA B but agroinoculation with DNA A alone resulted in virus spread in 30% of the inoculated N. benthamiana plants. Leaf disc explants of N. benthamiana, tomato and potato could all be infected by agroinoculation indicating that the method of delivery of the DNA to intact potato plants was unsuitable for successful inoculation rather than an inherent inability of the virus to replicate/spread in potato per se. Neither whole plants nor leaf discs of sugar beet supported the replication of PYMV DNA.

Base Sequence↗

PubMed1990

Poly(dimethylsiloxane)-poly(ethylene oxide)-heparin block copolymers. III: Surface and bulk compositional differences.

Previously observed bioactivity of poly(dimethylsiloxane)-poly(ethylene oxide)-heparin (PDMS-PEO-Hep) triblock copolymers has prompted studies of the surface and bulk character of this copolymer using angular-dependent electron spectroscopy for chemical analysis (ADESCA), static secondary mass spectroscopy (SIMS), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Because the low-energy PDMS phase dominates surfaces of this copolymer when solvent cast under air or vacuum conditions, attempts were made to explain surface restructuring and rearrangements induced in hydrated or aqueous environments that permit surface accessibility and bioactivity of heparin moieties. Based on comparisons with PDMS, PEO, and heparin homopolymers, PEO/heparin blends, and an unheparinized PDMS-PEO diblock copolymer, PDMS-PEO-heparin demonstrates both phase-mixed and phase-separated regions in DSC analysis. During annealing cycles above the Tg values of the copolymer constituents, phase-mixed regions become increasingly phase separated and PEO enriched. TGA analysis confirmed the presence block copolymer constituents and presented evidence of intermolecular segmental interactions, hence phase-mixing in the copolymers. ADESCA analysis indicates that the outer 5 A of both the PDMS-PEO and PDMS-PEO-Hep copolymers is essentially pure PDMS. However, significant amounts of PEO are detected 5 to 20 A below the surface. Static SIMS also detects the presence of PDMS at the surfaces of the PDMS-PEO and PDMS-PEO-Hep copolymers. Compositional models based on ADESCA, SIMS, and DSC data are presented for desiccated and hydrated copolymer surfaces.

Biocompatible Materials↗

PubMed1970

Effects of nitroglycerin on left ventricular volumes and wall tension in patients with ischaemic heart disease.

Since the dimensions of the ventricles are related to both myocardial tension and myocardial oxygen consumption (MVO2), the effects of nitroglycerin on the left ventricular volumes and left ventricular haemodynamics were studied in patients with ischaemic heart disease. The ventricular volumes were estimated using the constant infusion technique (indocyanine green) of Shaffer (1964). Sublingual administration of nitroglycerin (0.6 mg.) resulted in a significant reduction in cardiac output (27%), mean systolic pressure (21%), left ventricular end-diastolic pressure (63%), stroke volume (27%), left ventricular end-diastolic volume (26%), and left ventricular work (41%). Both calculated circumferential myocardial force (40%) and the myocardial tension (33%) decreased during systole, while the pressure-time index decreased by 27%. A similar decrease was also found in the contractile element work (42%), and mean circumferential fibre shortening rate (22%). Thus, this study has shown that the major determinants of MVO2, i.e. myocardial wall tension, the velocity of contraction, and contractile element work, decrease significantly after administration of nitroglycerin.

Angina Pectoris↗