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Biomedical subjects

S C Kim

Publications and source records attributed to S C Kim.

At least 37 records · Page 2Linked to original sources

A double-blind, randomised- placebo, controlled, parallel group, multicentre, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea.

The efficacy and safety of sildenafil was evaluated in a randomiSed, double-blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months duration. A total of 133 patients were randomised at six centres in Korea to receive either sildenafil (50 mg initially, increased if necessary to l00 mg or decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual activity for a period of 8 weeks. At the end of this time, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the International Index of Erectile Function (IIEF) scale, (2) the percentage of successful intercourse attempts, and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P&<0.0001). Treatment-related adverse events occurred in 56.1% of patients receiving sildenafil and 20.9% receiving placebo. The most common adverse events with sildenafil were vasodilatation (flushing), headache and abnormalities in colour vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in this population of Korean men appears similar to that reported in other studies in western populations.

Adult↗

Mutational analysis of forkhead transcriptional factor 2 (FOXL2) in Korean patients with blepharophimosis-ptosis-epicanthus inversus syndrome.

We screened for mutations in the forkhead transcription factor gene, FOXL2, in Korean patients with sporadic or familial blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and direct sequencing. Five of nine BPES families and three of seven sporadic cases were detected to have FOXL2 mutations. We identified four types of FOXL2 mutations, two of which are novel. A new 14 bp deletion (939-952del14) causing a frameshift from G235W and the extension of the predicted protein to 527 amino acids was detected in a BPES family patient. In addition, a novel 845C > A transversion, resulting in a nonsense mutation (S203X), was found in a sporadic case of BPES. The previously reported in-frame 30 bp duplication (909-938dup30) was the most common mutation and was found in eight patients of four BPES families and one sporadic case. A known 17 bp duplication (1080-1096dup17) was observed in a sporadic BPES case. We were unable to find a causal mutation in four BPES families and four sporadic cases. These results suggest that in a fraction of BPES patients, the genetic defect might be associated with a mutation in the non-coding region of the FOXL2 gene or in other genes.

Adolescent↗

Preference for oral sildenafil or intracavernosal injection in patients with erectile dysfunction already using intracavernosal injection for > 1 year.

UNLABELLED: Authors from Seoul describe their experience with patients already on triple therapy by intracavernosal injection who changed to oral sildenafil. Rather surprisingly, they found that patients had had a greater preference than expected for triple therapy, feeling that they had a better quality of erection on intracavernosal injection. The subject of the effect of renal transplantation on sperm quality and sex hormone levels is discussed by authors from Teheran. They found that sperm morphology and density remained unchanged, but there were significant improvements in sperm mobility. There was also an improvement in hormone levels and sexual function. OBJECTIVE: To investigate the efficacy and preference for oral sildenafil or intracavernosal injection (ICI) therapy in patients with erectile dysfunction (ED) already using ICI. PATIENTS AND METHODS: In all, 69 patients with ED (mean age 55.1 years, sd 12.3) on ICI therapy with triple solution (papaverine/phentolamine/prostaglandin-E1) for > 1 year were recruited for the study. Their erection quality, adverse reactions and selection rate of oral sildenafil or ICI as treatment, after using sildenafil for 3 months, and the reasons for their preferences, were compared between the regimens, RESULTS: Overall, 52 men (75%) responded to sildenafil; of these men, the erection quality with ICI was better than that with sildenafil in 46 (89%) and 16 (31%) preferred ICI as their treatment. Eighteen patients (35%) used each treatment alternately and 18 (35%) used sildenafil exclusively. The main reason given by patients for choosing ICI was a better quality of erection (74%). CONCLUSION: More patients with ED and using ICI preferred it as their main treatment than was expected, even though they had a good response to oral sildenafil. A better quality of erection with ICI was the reason why experienced patients chose this method, differing from the choice of patients starting treatment for ED.

Administration, Oral↗

Study on the inhibitory effects of Korean medicinal plants and their main compounds on the 1,1-diphenyl-2-picrylhydrazyl radical.

A 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-generating system was used to evaluate the antioxidant properties of Korean medicinal plants that have been used widely as folk medicines for several disorders, as well as compounds isolated from them. Among the Rosaceae, Rosa rugosa and Rosa davurica showed strong DPPH radical-scavenging activity. The most effective medicinal plant from families other than Rosaceae was Cedrela sinensis, followed in order by Nelumbo nucifera, Eucommia ulmoides, Zanthoxylum piperitum, Cudrania tricuspidata and Houttuynia cordata. These results serve as a good index of the free radical-scavenging activities of Korean medicinal plants. Furthermore, the polyphenols isolated from these plants, procyanidin B-3, (+)-catechin, gallic acid, methyl gallate, quercetin, quercetin-3-O-beta-D-glucoside, quercetin-3-O-beta-galactoside, quercetin-3-O-rutinose and kaempferol, exerted strong DPPH radical-scavenging activity. These results suggest that the Korean medicinal plants and the polyphenols isolated from them that exhibited effective radical-scavenging activity may be promising agents for scavenging free radicals and treating diseases associated with excess free radicals.

Biflavonoids↗

Effect of synthesis temperature of PEO-grafted PU/PS IPNs on surface morphology and in vitro blood compatibility.

When hydrophilic/hydrophobic polymers have a microdomain structure, platelet adhesion and activation are effectively suppressed by prohibition of the excessive assembly of glycoproteins and adenosine triphosphate (ATP) consumption of the platelets on the surface. In this study, poly(ethylene oxide)-grafted hydrophilic polyurethane (PU)/hydrophobic polystyrene (PS) interpenetrating polymer networks (IPNs) were synthesized by varying the synthesis temperature to control the phase separation and the microdomain surface structure, and the effect of the degree of phase separation on the in vitro blood compatibility. The size of the dispersed PS-rich domains in the PU-rich matrix decreased, and the hydrophilicity also decreased as the synthesis temperature of the PS network during the IPN synthesis was decreased, as the phase separation was suppressed during the synthesis. The amount of the adsorbed bovine plasma fibrinogens (BPF) on the PEO-grafted PU/PS IPNs decreased as the synthesis temperature was decreased, and the in vitro adhesion of the platelets was also suppressed on the PEO-grafted PU/PS IPNs prepared at lower temperature. The microdomain structure on the surface affected the adhesion and the activation of the adhered platelets, and the suppression of the phase separation resulted in the decrease of the domain size, which also enhanced the blood compatibility of the PEO-grafted PU/PS IPNs.

Animals↗

Adhesion and growth of endothelial cell on amphiphilic PU/PS IPN surface: effect of amphiphilic balance and immobilized collagen.

Since natural blood vessels are lined with an endothelial cell (EC) monolayer, it is proposed that synthetic biomaterial surfaces be covered or seeded with endothelial cells for ideal nonthrombogenicity under normal conditions. The effects of the surface energy of hydrophilic-hydrophobic IPN on EC adhesion and growth were investigated. The human umbilical vein endothelial cells (HUVECs) were cultured on polyurethane (PU)/polystyrene (PS) IPN prepared by changing only the amphiphilic balance and controlling the microphase separated surface structure. The collagens were immobilized on the IPN surfaces for enhanced adhesion of HUVECs, and the morphology of the collagens immobilized highly depended on the surface energy of the IPNs. The stranded rope structure of the collagen molecules in the solution state was maintained only on the surface of the IPN with intermediate hydrophilicity. The adhesion and the proliferation of ECs on the nontreated IPN surfaces increased by increasing the hydrophobicity of the IPNs, and they were optimized on the collagen-treated IPN surface having an intermediate hydrophilicity. Finally, platelet adhesion was significantly reduced on the EC-hybridized surface of the IPNs.

Cell Adhesion↗

Enhanced expression of tandem multimers of the antimicrobial peptide buforin II in Escherichia coli by the DEAD-box protein and trxB mutant.

The tandem multimeric expression of various peptides has been explored by many researchers. However, expression levels have usually not been proportional to the degree of multimerization. To increase the expression level in Escherichia coli of tandem multimers of a cationic antimicrobial peptide, buforin II, fused to an anionic peptide, we studied the effect of the DEAD-box protein and the trxB mutant on the expression of tandem multimers. An expression vector with a tac promoter was more effective in directing multimeric expression than one with a T7 promoter. The expression level of large multimers was substantially increased with the tac promoter, possibly through stabilization of long transcripts by synchronization of transcription and translation. Coexpression of the DEAD-box protein, an RNA-binding protein, with the T7 expression system increased the expression level of multimers, especially large multimers, due to protection of the long RNA transcripts. In addition, the use of the trxB mutant also enhanced the expression level of tandem multimers, which contain two cysteine residues at both ends of the monomeric unit. It seems that disulfide bonds formed in the multimers in the trxB mutant might help efficient charge neutralization for inclusion body formation of the multimers, resulting in enhancement of expression. Our results show that the expression of multimers can be improved through the stabilization of the long transcripts by the DEAD-box protein or the expression, under an oxidizing environment, of the trxB mutant in which covalent cross-links through disulfide bonds facilitate inclusion body formation of the multimeric fusion peptide.

Anti-Bacterial Agents↗

Root canal length measurement in teeth with electrolyte compensation.

Electronic root canal length measurement devices have made it easier and faster to measure the root canal length of a tooth compared with the conventional radiographic method. Of these electronic apex locators, the frequency-dependent type features greater accuracy and convenience in operation. However, its accuracy is still influenced by the presence of blood and/or the various electrolytes used in root canal therapy. This study describes the development of a new frequency-dependent electronic apex locator featuring electrolyte compensation, utilising an impedance ratio and voltage difference technique to minimise the influence of electrolytes on the accuracy of root canal length measurement. The errors for distances from file tips to apical constrictions were determined in vivo with the device operating with electrolyte compensation. The measured lengths were compared with the true lengths of the extracted teeth determined using a microscope. The mean error was +0.14+/-0.27mm, and 95.2% of the measurements were within the clinical tolerance of +/-0.5mm. It was also found that the degree of accuracy was not dependent on the size of the apical foramen (p = 0.74).

Dental Pulp Cavity↗

PEO-grafting on PU/PS IPNs for enhanced blood compatibility--effect of pendant length and grafting density.

Polyurethane (PU) homopolymers and PU/polystyrene (PS) interpenetrating polymer networks (IPNs) were successfully synthesized changing the length of the pendant poly(ethylene oxide) (PEO) chains and the grafting density of PEO chains. All the PU/PS IPNs had the microphase-separated structures in which the PS-rich phase domains were dispersed in the matrix of the PU-rich phase. The domain size decreased a little, as the degree of grafting with PEO chains was increased. The water swelling ratio increased, and the interfacial energy decreased, as the length of the pendant PEO chains, and the grafting density of PEO chains of the PEO-grafted PU/PS IPNs were increased, since the mobile hydrophilic pendant PEO chains effectively induced and absorbed the water, when they were contacted with water. The hydrophilic and highly concentrated pendant PEO chains could easily prohibit the adhesion of the fibrinogens and the platelets on the surface, and the blood compatibility of IPNs was enhanced by increasing of grafting with PEO chains. The adsorption of the fibrinogens and the platelets was suppressed, as the length of pendant PEO chains, and the grafting density were increased.

Adsorption↗

Adsorption properties of a colloid-polymer mixture confined in a slit pore.

The soft fundamental-measure theory, which was based on the additive colloid-polymer mixture [M. Schmidt, Phys. Rev. E 62, 3799 (2000)] has been employed to investigate the adsorption of a colloid-polymer mixture within a hard slit pore. The calculated results show that the adsorption for the confined colloid-polymer mixture is very different from those of the colloid-colloid and polymer-polymer mixtures. The equilibrium particle density distribution strongly depends on the softness of a star polymer. The local relative concentration oscillates with a spatial period close to the diameter of a large particle in the same way as the equilibrium particle density distribution. The size selectivity in adsorption depends both on the softness of a star polymer and on the particle size ratio in a binary mixture. In particular, the strong adsorption occurs at the ultra-soft polymer and high bulk packing fraction.

Journal Article↗

Objective evaluation of treatment effects on port-wine stains using L*a*b* color coordinates.

Wide variations in port-wine stains and their responses to various therapies pose a need for the development of an objective method to evaluate the effects of treatment. Several techniques such as laser Doppler, reflectance spectrometry, and tristimulus colorimetry have been used to evaluate the color of port-wine stains, but these techniques are limited by cost, small test size area, and other factors. Therefore, we developed a simple and cost-effective method of evaluating treatment results on port-wine stains using the L*a*b* color coordinate system in combination with a personal computer. For 22 patients with port-wine stains, the slide photographs were digitized using a slide scanner. L*a*b* color differences of the normal control and port-wine stain sites were obtained before and after treatment, and treatment effect (percent) was calculated. By calculating each color difference between the lesion and normal skin both before and after treatment, problems arising from different illuminating conditions during photography were minimized. The results were compared with the visual evaluation conducted by three experienced plastic surgeons. The treatment effects analyzed by L*a*b* color coordinate ranged from 4 to 95 percent, with a mean of 48.1 percent, whereas treatment effects evaluated by the plastic surgeons ranged from 15 to 92 percent, with a mean of 51.1 percent. The subjective clinical grades correlated well with the treatment effects obtained by the proposed color analysis system (correlation coefficient, 0.89). The maximum difference in the effect of treatment for a patient evaluated by the three clinicians was up to 60 percent, which means that visual judgment is very subjective and variable. The color analysis system proposed as a result of this study is very easy, objective, quantitative, cost-effective, and can be useful for the evaluation of treatment effects on colored skin lesions such as port-wine stains.

Color↗

p53 and its homologues, p63 and p73, induce a replicative senescence through inactivation of NF-Y transcription factor.

Recent studies have identified two p53 homologues, p63 and p73. They activate p53-responsive promoters and induce apoptosis when overexpressed in certain human tumors. Here, we report that p63, like p53 and p73, induces replicative senescence when expressed in a tetracycline-regulated manner in EJ cells lacking a functional p53. In addition to transcription activation of p53-responsive genes, we found that p63 and p73 repress transcription of the cdk1 and cyclin B genes, both of which are irreversibly repressed in senescent human fibroblast. In transient transfection assay, p63 and p73 repress the cdk1 promoter regardless of the presence of a dominant negative mutant form of p53. Furthermore, we found that DNA binding activity of NF-Y transcription factor, which is essential for transcription of the cdk1 and cyclin B genes and inactivated in senescent fibroblast, is significantly decreased by expression of either of p53, p63, or p73. Since NF-Y binds to many promoters besides the cdk1 and cyclin B promoters, inactivation of NF-Y by p53 family genes may be a general mechanism for transcription repression in replicative senescence.

CCAAT-Binding Factor↗

Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma.

MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9 -positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at -74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at -74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at -74 bp. These findings suggest that hypomethylation of the CpG at -74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC.

Carcinoma, Renal Cell↗

An enzyme-linked immunosorbent assay for the Raf/MEK1/MAPK signaling cascade.

The Ras-MAPK signaling cascade transmits mitogenic stimuli from growth factor receptors and activated Ras to the cell nucleus. Inappropriate Ras activation is associated with approximately 30% of all human cancers. The kinase components of the Ras-MAPK signaling cascade are attractive targets for pharmaceutical intervention. Therefore, we have developed a high-throughput, nonradioactive ELISA method to monitor Raf and MEK1 kinase activity. In this assay system activated Raf phosphorylates and activates MEK1, which in turn phosphorylates MAPK. Antibodies that specifically detect phosphorylated MAPK (vs. nonphosphorylated MAPK) made enzyme-linked immunosorbent assay (ELISA) development possible. This assay detects inhibitors of Raf and/or MEK1 and has been used to screen large numbers of random compounds. The specific target of inhibition in the Raf/MEK1/MAPK ELISA can be subsequently identified by secondary assays which directly measure Raf phosphorylation of MEK1 or MEK1 phosphorylation of MAPK.

Enzyme-Linked Immunosorbent Assay↗

MEK (MAPKK) inhibitors. Part 2: structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines.

A series of 4-anilino-3-cyano-6,7-dialkoxyquinolines with different substituents attached to the 4-anilino group has been prepared that are potent MEK (MAP kinase kinase) inhibitors. The best activity is obtained when a phenyl or a thienyl group is attached to the para-position of the aniline through a hydrophobic linker, such as an oxygen, a sulfur, or a methylene group. The most active compounds show low nanomolar IC(50)'s against MEK (MAP kinase kinase), and have potent growth inhibitory activity in LoVo cells (human colon tumor line).

Aniline Compounds↗

In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy.

Although the current clinical formulation of paclitaxel (Taxol) has a promising clinical activity against a wide variety of tumors, it has significant toxic side effects, some of which are associated with its formulation in a 1:1 (v/v) mixture of Cremophor EL and dehydrated alcohol. One of the problems associated with the intravenous administration of paclitaxel is its low solubility in water. Our study was designed to evaluate the pharmacokinetics, tissue distribution, toxicity and efficacy of a paclitaxel (Genexol)-containing biodegradable polymeric micellar system (Genexol-PM) in comparison to Taxol. Genexol-PM was newly developed by using a low molecular weight, nontoxic and biodegradable amphiphilic diblock copolymer, monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) and paclitaxel (Genexol, Samyang Genex Co., Seoul, Korea). In a human cancer cell line model, Genexol-PM and Taxol showed comparable in vitro cytotoxicity against human ovarian cancer cell line OVCAR-3 and human breast cancer cell line MCF7. The maximum tolerated dose (MTD) of Genexol-PM and Taxol in nude mice was determined to be 60 and 20 mg/kg, respectively. The median lethal dose (LD(50)) in Sprague--Dawley rats was 205.4 mg/kg (male) and 221.6 mg/kg (female) for Genexol-PM, while 8.3 mg/kg (male) and 8.8 mg/kg (female) for Taxol. After intravenous administration of Genexol-PM in murine B16 melanoma-induced female SPF C57BL/6 mice at a dose of 50 mg/kg, the area under the plasma concentration-time curve (AUC) was similar to Taxol((R)) at a dose of 20 mg/kg, but biodistribution of paclitaxel after administration of Genexol-PM showed 2 to 3-fold higher levels in tissues including liver, spleen, kidneys, lungs, heart and tumor as compared to Taxol. The in vivo antitumor efficacy of Genexol-PM as measured by reduction in tumor volume of SKOV-3 human ovarian cancer implanted in nude (nu/nu) athymic mice and MX-1 human breast cancer implanted in Tac:Cr:(NCr)-nu athymic mice was significantly greater than that of Taxol. The results of cytotoxicity, MTD, LD(50) and antitumor efficacy suggest that Genexol-PM may have a great advantage over present-day chemotherapy with Taxol.

Animals↗

Orthophosphate anion enhances the stability and activity of endoxylanase from Bacillus sp.

Endoxylanase, for which the optimum temperature is 60 degrees C (optimum pH 7), is labile to heat. Because the isoelectric point (pI) value of this xylanase is 10.6, the net charge of this enzyme is positive at pH 7. Thus, ions are likely to influence its enzyme structure and the thermal stability of endoxylanase may improve. Among the various ions tested, orthophosphate anion (HPO(4)(2-)) was found to significantly improve not only the stability but the activity of xylanase. When K(2)HPO(4) concentration was increased from 50 mM to 1.2 M, the T(m )value of xylanase was increased from 60.0 degrees C to 74.5 degrees C. The affinity of xylanase on xylan also increased along with K(2)HPO(4) concentration. Thus, the xylanase activity at 0.6 M K(2)HPO(4) was 2.3-fold higher than that at 50 mM K(2)HPO(4), and 120.2-fold higher than that in 40 mM MOPS buffer. This enhanced activity in the presence of K(2)HPO(4 )probably takes place because the orthophosphate anion affects the binding and catalytic residues of endoxylanase.

Anions↗

Results on preemptive or prophylactic treatment of lamivudine in HBsAg (+) renal allograft recipients: comparison with salvage treatment after hepatic dysfunction with HBV recurrence.

BACKGROUND: Lamivudine has been reported to be able to stabilize liver enzyme and hepatitis B virus (HBV) replication with recurrent hepatitis that has been regarded as a frequent and major risk factor for hepatic dysfunction and chronic liver disease in renal transplant recipients. Because large number of hepatitis antigenemia patients among renal transplant patients experience recurrent hepatic dysfunction with HBV recurrence and permanent histological deterioration, preemptive or primary prophylactic use of lamivudine before transplantation may be more beneficial than a trial for the treatment of advanced hepatic dysfunction. METHODS: We conducted a double arm study to compare the efficacy of lamivudine between the preemptive (HBV DNA positive) or prophylactic (HBV DNA negative) trial for the maintenance of stable liver function (n=10) and the trial for the salvage of advanced hepatic dysfunction developed after renal transplantation (n=6) in hepatitis B viremia carrier renal transplant recipients. RESULTS: Hepatic dysfunction with recurrent HBV antigenemia developed in 11 of 36 (30.6%) hepatitis antigenemia patients with a mean duration of 8.4 months (range 5-19.4 months). In six patients treated with lamivudine after hepatic dysfunction from recurrent hepatitis B viremia, serum AST and ALT level normalized within 1 month and HBV-DNA disappeared in all cases. HBV-DNA, however, reappeared in three (50%) without any discontinuation of lamivudine. Liver biopsy revealed recurrent chronic active hepatitis with severe activity of fibrosis in four cases, cholestatic fibrosing hepatitis in one, and permanent cirrhotic change in one. In seven patients who had preemptive lamivudine treatment at 9, 6, 2, 2, 1, 0, 0 month before the transplantation, HBV-DNA had converted to negative with a mean follow up of 1.2 months (range 1-2 month) in all case. Three patients who had prophylactic trials with lamivudine have all remained HBV-DNA negative. The recurrence rate of HBV viremia in the preemptive or prophylactic lamivudine treated group is 10.0% (1/10), which is significantly lower than that (42.3%, 11/25) in the nonlamivudine-treated group. The re-recurrence rate of HBV viremia was significantly higher (3/6, 50.0%) in the reactive lamivudine treated group than in prophylactic or preemptive group (1/10, 10%). CONCLUSION: Although lamivudine treatment after hepatic dysfunction can be a sound conventional treatment modality, this preliminary study may suggest that preemptive or prophylactic trial of lamivudine before hepatic dysfunction might be a more effective strategy for prevention of permanent histological deterioration and recurrence of hepatitis B viremia.

DNA, Viral↗