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Biomedical subjects

K S Park

Publications and source records attributed to K S Park.

At least 19 recordsLinked to original sources

Observation of B+ --> Lambda c+ Lambda c- K+ and B0 --> Lambda c+ Lambda c- K0 decays.

We report the first measurements of the doubly charmed baryonic B decays B --> Lambda c+ Lambda c- K. The B+ --> Lambda c+ Lambda c- K+ decay is observed with a branching fraction of (6.5(-0.9)(+1.0)+/-1.1+/-3.4)x10(-4) and a statistical significance of 15.4sigma. The B0 --> Lambda c+ Lambda c- K0 decay is observed with a branching fraction of (7.9(-2.3)(+2.9)+/-1.2+/-4.1)x10(-4) and a statistical significance of 6.6sigma. The branching fraction errors are statistical, systematic, and the error resulting from the uncertainty of the Lambda c+ --> pK- pi+ decay branching fraction. The analysis is based on 357 fb(-1) of data accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ e- collider.

Journal Article↗

Sp1 mediates repression of the resistin gene by PPARgamma agonists in 3T3-L1 adipocytes.

Resistin is an adipokine related to obesity and insulin resistance. Expression of the resistin gene is repressed by the treatment of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, thiazolidinediones (TZDs). In this study, we investigated the mechanism by which TZDs inhibit the resistin gene expression. Resistin gene expression was decreased by TZD in fully differentiated 3T3-L1 adipocytes, which was abolished after treatment of cycloheximide (a protein synthesis inhibitor). TZD could not repress the expression of the resistin gene in the presence of mithramycin A (an Sp1 binding inhibitor). Sp1 binding site of the resistin promoter (-122/-114bp) was necessary for the repression. Further investigation of the effect of TZDs on the modification of Sp1 showed that the level of O-glycosylation of Sp1 was decreased in this process. These results suggest that PPARgamma activation represses the expression of the resistin gene by modulating Sp1 activity.

3T3-L1 Cells↗

Common promoter polymorphism in monocyte differentiation antigen CD14 is associated with serum triglyceride levels and body mass index in non-diabetic individuals.

AIMS: Growing evidence supports the hypothesis that chronic low-grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses. METHODS: We have sequenced the gene, including all exons, exon/intron boundaries, and the -1.5 kb of the 5' flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study. RESULTS: Eight polymorphisms, including four non-synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (-260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 +/- 0.81 vs. 1.46 +/- 0.80 mmol/l; P = 0.0007) and BMI (23.96 +/- 3.00 vs. 23.28 +/- 3.22 kg/m(2); P = 0.04) as compared with subjects carrying T/T genotypes. CONCLUSION: Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism-mediated genetic propensity to non-specific inflammatory responses.

Base Sequence↗

Putative association of peroxisome proliferator-activated receptor gamma co-activator 1beta (PPARGC1B) polymorphism with Type 2 diabetes mellitus.

AIMS: Peroxisome proliferator-activated receptor gamma co-activator 1beta (PPARGC1B) may play an important role in obesity and Type 2 diabetes mellitus (T2DM). In an effort to identify genetic polymorphisms in potential candidate genes for T2DM, genetic associations of PPARGC1B were examined in a Korean T2DM study. METHODS: We have sequenced the PPARGC1B, and examined its association with T2DM and diabetic phenotypes in a Korean T2DM study (775 T2DM patients and 316 control subjects) using the TaqMan method. Logistic and multiple regression models were employed to analyse the genetic contributions of polymorphisms. Nineteen polymorphisms were identified in PPARGC1B. RESULTS: By logistic regression analysis controlling for age and sex as covariates, one non-synonymous single-nucleotide polymorphism (SNP; +102605C>A; Arg292Ser) in exon 5 showed marginal significant associations with the risk of T2DM. The allele frequency of the minor allele ['A (= Ser)' allele of +102605C>A] was lower among T2DM patients (frequency = 0.101) than among control subjects (frequency = 0.135) [P = 0.03, OR = 0.71 (95% CI: 0.51-0.94)]. Furthermore, serum triglyceride level was also associated with this non-synonymous SNP (+102605C>A; Arg292Ser) in exon 5 among controls (P = 0.03 in the dominant analysing model). Serum triglyceride levels [1.46 +/- 0.70 (log-transformed value; 0.12 +/- 0.18)] were lower in individuals who carry one or two copies of minor alleles than among others [1.60 +/- 0.85 (log-transformed value; 0.16 +/- 0.21)]. CONCLUSION: The present study provides, for the first time, information about genetic polymorphisms in PPARGC1B and putative associations of one non-synonymous SNP with the risk of T2DM and serum triglyceride (TG) levels in the Korean population, although this result was not significant after correction for multiple testing.

Asian People↗

Association of a polymorphism in the gene encoding phosphoenolpyruvate carboxykinase 1 with high-density lipoprotein and triglyceride levels.

AIMS/HYPOTHESIS: Phosphoenolpyruvate carboxykinase (PCK) is the key enzyme involved in the regulation of gluconeogenesis. The aim of this study was to identify genetic polymorphisms in potential candidate genes for type 2 diabetes by sequencing all exons in the PCK genes (PCK1 and PCK2), and examining the association with type 2 diabetes and diabetic phenotypes in a Korean population (775 type 2 diabetic patients and 316 normal control subjects). MATERIALS AND METHODS: Twenty-two polymorphisms in PCK1 and PCK2 were identified in a Korean population (n=24) by direct DNA sequencing. The TaqMan genotyping method was applied for genotyping the remainder of the study population. Associations of PCK polymorphisms with the risk of type 2 diabetes and diabetic phenotypes were analysed using logistic and multiple regressions, adjusting for age, sex and BMI. RESULTS: Although no significant associations between the genetic polymorphisms in PCK genes and the risk of type 2 diabetes were detected, in further haplotype analysis, one of the common haplotypes, PCK1 ht3, revealed susceptibility to type 2 diabetes (p=0.006). One 3' untranslated region (UTR) single nucleotide polymorphism (SNP) also showed an association with HDL levels among non-diabetic control subjects: individuals homozygous for the major allele (T/T) had the lowest HDL level (1.11+/-0.32 mmol/l), heterozygotes (T/C) had an intermediate level (1.27+/-0.37 mmol/l), and those homozygous for the minor allele (C/C) had the highest level (1.39+/-0.28 mmol/l) (p=0.000003). This 3' UTR SNP was also associated with triglyceride levels, with a lower triglyceride level observed among individuals who were homozygous for the minor allele (C/C) than among those who were not. CONCLUSIONS/INTERPRETATION: The strong genetic association of HDL and triglyceride levels with variation/haplotype information identified in this study would be useful for further genetic epidemiological studies of this important gene.

5' Flanking Region↗

Association between polymorphisms in the nuclear respiratory factor 1 gene and type 2 diabetes mellitus in the Korean population.

AIMS/HYPOTHESIS: Dysfunction in mitochondrial oxidative phosphorylation plays a central role in insulin resistance and type 2 diabetes. Nuclear respiratory factor 1 (NRF1) is a transcription factor that acts on nuclear genes encoding respiratory subunits and components of the mitochondrial transcription and replication machinery. Thus, we investigated its genetic association with type 2 diabetes. METHODS: The NRF1 gene was sequenced to identify polymorphisms in 24 Korean DNA samples and then common variants were genotyped in 766 patients with type 2 diabetes and 303 non-diabetic subjects. RESULTS: Twelve single nucleotide polymorphisms and one insertion/deletion polymorphism were identified. Six common variants among them were genotyped in a larger study. Although three individual polymorphisms appeared to be associated with type 2 diabetes (g.-46350insdel A, g.+141G>T and g.+54529A>G), the effects were only marginal. However, a haplotype (H2) was associated with a decreased risk of type 2 diabetes and another haplotype (H4) was associated with an increased risk of type 2 diabetes (p values for the Haplo. Score test were 0.009 and 0.004, respectively). CONCLUSIONS/INTERPRETATION: We demonstrated that two common haplotypes of NRF1 gene are associated with type 2 diabetes in the Korean population.

Aged↗

Peroxisome proliferator-activated receptor gamma coactivator 1 alpha promoter polymorphisms are associated with early-onset type 2 diabetes mellitus in the Korean population.

AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) is a transcriptional coactivator implicated in insulin release by beta cells and in insulin resistance. Therefore, genetic variation of PPARGC1A could be implicated in the onset of type 2 diabetes. In this study, we examined whether the PPARGC1A gene locus is associated with type 2 diabetes mellitus. We also investigated its association with clinical and metabolic parameters in healthy and diabetic subjects. METHODS: After sequencing exons and their boundaries of the PPARGC1A gene, including the promoter region ( approximately 1.5 kb), we genotyped eight common single nucleotide polymorphisms (SNPs) in an association study comprising 762 unrelated patients with type 2 diabetes and 303 non-diabetic control patients. We divided the patients with type 2 diabetes into quartiles or three groups according to age at diagnosis of type 2 diabetes (early-onset: <40 years of age, average-onset: 40< or = <60 years, and late-onset: > or =60 years). RESULTS: There was no strong association between SNPs or haplotypes of PPARGC1A and type 2 diabetes. However, the SNPs of g.-1789G>A and g.-1437C>T were associated with the age at diagnosis of type 2 diabetes (p=0.042 and p=0.032, respectively). In addition, the promoter SNPs of g.-1789G>A and g.-1437C>T and the haplotypes ht2 (-1789A and -1437T) were significantly associated with early-onset type 2 diabetes (p=0.002, p=0.001 and p=0.001, respectively). CONCLUSIONS/INTERPRETATION: Our results suggest that PPARGC1A promoter polymorphisms are associated with age at diagnosis of type 2 diabetes and early-onset type 2 diabetes in the Korean population.

Age of Onset↗

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site.

AIMS/HYPOTHESIS: Resistin is an adipokine that might link obesity and insulin resistance. A common polymorphism of the human resistin gene, -420C >G, is a major determinant of plasma resistin concentrations as well as resistin mRNA expression in human adipose tissue. In this study, we investigated the regulatory mechanism by which this polymorphism affects resistin expression. METHODS: Electrophoretic mobility shift assay was performed to identify the transcription factors binding to the -420G region. Transient transfection and reporter assay were used to measure promoter activities of the resistin gene. The binding ability of stimulatory protein 1 (Sp1) in response to adipocyte differentiation or high glucose concentrations was also measured. RESULTS: Sp1 and stimulatory protein 3 (Sp3) specifically bound to the region around -420G of the human resistin gene. Overexpression of Sp1 increased the promoter activity regardless of -420 genotypes, while the promoter activity of the -420G construct was two-fold higher than that of the -420C construct. In contrast, overexpression of Sp3 scarcely increased the promoter activity. The binding ability of Sp1 to the -420G region was increased in response to adipocyte differentiation. Mithramycin A, an inhibitor of DNA binding of Sp1, reduced the effect of high glucose on transcription induction of the resistin gene in adipocytes. CONCLUSIONS/INTERPRETATION: These results suggest that Sp1 is an important factor regulating transcription of human resistin gene. A common polymorphism of the human resistin promoter, -420C >G, is critical for the binding of Sp1 and modulates the transcriptional activity of the resistin gene by changing the binding ability of Sp1. In addition, Sp1 may be involved in the increase of resistin expression by hyperglycaemia.

3T3 Cells↗

Low-power hybrid wireless network for monitoring infant incubators.

We have created a pilot wireless network for the convenient monitoring of temperature and humidity of infant incubators. This system combines infrared and radio frequency (RF) communication in order to minimize the power consumption of slave devices, and we therefore call it a hybrid wireless network. The slave module installed in the infant incubator receives the calling signal from the host with an infrared receiver, and sends temperature and humidity data to the host with an RF transmitter. The power consumption of the host system is not critical, and hence it uses the maximum power of infrared transmission and continuously operating RF receiver. In our test implementation, we included four slave devices. The PC calls each slave device every second and then waits for 6 s, resulting in a total scan period of 10 s. Slave devices receive the calling signals and transmit three data values (temperature, moisture, and skin temperature); their power demand is 1 mW, and can run for about 1000 h on four AA-size nickel-hydride batteries.

Electric Power Supplies↗

Parametric image of myocardial blood flow generated from dynamic H2(15)O PET using factor analysis and cluster analysis.

Algorithm-based parametric imaging of myocardial blood flow (MBF), as measured by H2(15)O PET, has been the goal of many research efforts. A method for generating parametric images of regional MBF by factor and cluster analysis on H2(15)O dynamic myocardial PET was validated by its comparison with gold-standard MBF values determined invasively using radiolabelled microspheres. Right and left ventricular blood pool activities and their factor images were obtained by the application of factor analysis to dynamic frames. By subtraction of the factor images multiplied by their corresponding values on the factors from the original dynamic images for each frame, pure tissue dynamic images were obtained, from which arterial blood activities were excluded. Cluster analysis that averaged pixels having time-activity curves with the same shape was applied to pure tissue images to generate parametric MBF images. The usefulness of this method for quantifying regional MBF was evaluated using canine experiment data. H2(15)O PET scans and microsphere studies were performed on seven dogs at rest and after pharmacological stress. The image qualities and the contrast of parametric images obtained using the proposed method were significantly improved over either the tissue factor images or the parametric images obtained using a conventional method. Regional MBFs obtained using the proposed method correlated well with those obtained by the region of interest method (r = 0.94) and by the microsphere technique (r = 0.90). A non-invasive method is presented for generating parametric images of MBF from H2(15)O PET, using factor and cluster analysis.

Animals↗

Association of HYPA haplotype in the mannose-binding lectin gene-2 with Behçet's disease.

Behcet's disease (BD) is a multisystemic, recurrent inflammatory disease caused by the combinations of multiple genetic and environmental factors. Moreover, the MBL2 gene single-nucleotide polymorphisms and haplotypes are known to increase the susceptibility to inflammatory disease and to alter the serum levels of mannose-binding lectin (MBL. We postulated that the haplotypes of the MBL2 gene influence therapeutic response in BD, thus affecting the clinical symptoms in 282 BD patients. The promoter region, MBL2-550*C/*C (L/L) homozygote was found to have a lower frequency in BD patients than that in controls. No difference was observed in the allele frequencies of G-221C (Y/X), C+4T (P/Q) or Gly54Asp (A/B) of the MBL2 gene in BD patients and in controls. The HYPA haplotype contributed to BD occurrence, whereas the LYPA haplotype was negatively associated with BD. BD patients with several symptoms and with an earlier disease-onset age had a higher HYPA haplotype frequency. BD patients showing poor response (S) to therapy had a higher HYPA frequency than those showing good response (M). It seems that possessing HYPA increases the risk of BD and that the MBL2 HYPA haplotype plays a role in MBL levels and increases the susceptibility to BD.

Adolescent↗

Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population.

AIMS: To investigate any association between Type 2 diabetes mellitus and two single nucleotide polymorphisms (SNPs) in the adiponectin gene, T45G and G276T, in the Korean population. METHODS: We genotyped 427 non-diabetic controls and 493 Type 2 diabetic patients for SNPs T45G and G276T of adiponectin gene, measured plasma adiponectin concentrations, and examined clinical parameters in Koreans. RESULTS: There were no statistically significant differences in allele frequencies of SNPs 45 and 276 comparing control with Type 2 diabetic subjects (T frequency 68.3% vs. 71.6%, P=0.13 for SNP45, G frequency 72.2% vs. 68.9%, P=0.12 for SNP276). The genotype distributions of these SNPs had no association with the risk of Type 2 diabetes and metabolic parameters of insulin resistance. Plasma levels of adiponectin were not statistically different according to T45G and G276T either, in both control and Type 2 diabetic subjects. CONCLUSION: The T45G and G276T of the adiponectin gene may not be an important determinant of Type 2 diabetes or insulin resistance in Korean subjects.

Adiponectin↗

Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are associated with Type 2 diabetes mellitus and obesity in the Korean population.

AIMS: We examined whether the common polymorphisms of the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene are associated with Type 2 diabetes or obesity in the Korean population. METHODS: We genotyped two common PPARgamma polymorphisms (Pro12Ala and 161C > T) and examined their association with the clinical phenotypes found in 684 patients with Type 2 diabetes mellitus and 291 non-diabetic control subjects. RESULTS: The 12Ala allele was less frequent in the Type 2 diabetic patients than in the non-diabetic control subjects (0.036 vs. 0.053, P = 0.024). The allele frequencies of the 161C > T polymorphism did not differ between the control and Type 2 diabetic group (0.158 vs. 0.173). In the non-diabetic controls, those with the T allele had lower BMI and fasting serum triglyceride (TG) concentrations than those with the C/C homozygote (22.7 +/- 2.9 vs. 23.8 +/- 3.2 kg/m2, P = 0.002; 1.45 +/- 0.81 vs. 1.65 +/- 0.83 mmol/l, P = 0.03, respectively). The 12Ala-161T haplotype was associated with a decreased risk for Type 2 diabetes (OR = 0.47, P = 0.009), whereas the 12Pro-161T haplotype was associated with lower BMI and lower fasting serum TG (22.5 +/- 2.8 vs. 23.7 +/- 3.2 kg/m2, P = 0.004; 1.41 +/- 0.87 vs. 1.64 +/- 0.79 mmol/l, P = 0.02, respectively). CONCLUSIONS: The PPARgamma 12Ala allele was associated with a reduced risk of Type 2 diabetes, whereas the PPARgamma 161T allele was associated with lower BMI and fasting serum TG concentrations in the Korean subjects. The subjects with 12Ala-161T haplotypes had a reduced risk of Type 2 diabetes.

Alleles↗

Effects of Panax ginseng extract on exercise-induced oxidative stress.

AIM: This study was designed to study the effects of Panax ginseng extract (PGE) on lipid peroxidation and scavenger enzymes induced by an acute exhaustive exercise in sedentary humans. METHODS: Seven healthy male subjects performed 2 exhaustive incremental exercises on the treadmill before and after 8 weeks' PGE ingestion (2 g each time, 3 times a day) as the control and PGE exercise, respectively. VO2, HR, and exercise duration during exercise were measured. Blood samples were collected at rest, and immediately, 10 and 30 min after each test and used to measure malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD). RESULTS: PGE administration significantly increased exercise duration until exhaustion by 1.5 min (p<0.05). MDA was significantly elevated following both trials (p<0.01), however, it was attenuated after PGE administration (p<0.01). CAT and SOD activities following exercise were significantly elevated, but the activities following control exercise were much lower than those following PGE exercise. CONCLUSIONS: These results suggest that the elevation in CAT and SOD activities as scavenger enzymes after PGE administration result in decrease of MDA level as one of PGE action mechanisms and consequently, prolong exercise duration until exhaustion. These findings support scientific claims that ginseng has ergogenic properties in facilitating recovery from exhaustive exercise.

Adolescent↗

Search for the lepton-flavor-violating decay tau- -->micro-eta at Belle.

We have searched for the lepton flavor violating decay tau(-)-->micro(-)eta using a data sample of 84.3 fb(-1) accumulated with the Belle detector at KEK. The eta meson was detected through the decay modes: eta-->gammagamma and pi(+)pi(-)pi(0). No signal candidates are found, and we obtain an upper limit for the branching fraction B(tau(-)-->micro(-)eta)<3.4 x 10(-7) at the 90% confidence level.

Journal Article↗

Observation of the radiative decay D0-->phigamma.

We report the observation of the decay D0-->phigamma with a statistical significance of 5.4sigma in 78.1 fb(-1) of data collected by the Belle experiment at the KEKB e+e- collider. This is the first observation of a flavor-changing radiative decay of a charmed meson. The Cabibbo- and color-suppressed decays D0-->phipi(0), phieta are also observed for the first time. We measure branching fractions B(D0-->phigamma)=[2.60(+0.70)(-0.61)(stat)+0.15-0.17(syst)] x 10(-5), B(D0-->phipi(0))=[8.01+/-0.26(stat)+/-0.47(syst)] x 10(-4), and B(D0-->phieta)=[1.48+/-0.47(stat)+/-0.09(syst)] x 10(-4).

Journal Article↗

Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.

AIMS/HYPOTHESIS: Resistin is thought to be an important link between obesity and insulin resistance. It has been suggested that genetic polymorphism in the promoter of resistin gene is a determinant of resistin mRNA expression and possibly associated with obesity and insulin resistance. In this study, we investigated the association between the genotype of resistin promoter and its plasma concentrations. METHODS: We examined g.-537A>C and g.-420C>G polymorphisms in the resistin promoter and measured plasma resistin concentrations in Korean subjects with or without Type 2 diabetes. We also did haplotype-based promoter activity assays and the gel electrophoretic mobility shift assay. RESULTS: The -420G and the -537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with haplotype A-G (-537A and -420G) had significantly higher plasma resistin concentrations than the others. Haplotype A-G had modestly increased promoter activity compared to the other haplotypes. Electrophoretic mobility shift assay showed that the -420G allele is specific for binding of nuclear proteins from adipocytes and monocytes. However, none of the two polymorphisms were associated with Type 2 diabetes or obesity in our study subjects. CONCLUSIONS/INTERPRETATION: Polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.

Aged↗

Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is a complex genetic disease, which results from interactions between multiple genes and environmental factors without any single factor having strong independent effects. This study was done to identify gene to gene interactions which could be associated with the risk of Type 2 diabetes. METHODS: We genotyped 23 different loci in the 15 candidate genes of Type 2 diabetes in 504 unrelated Type 2 diabetic patients and 133 non-diabetic control subjects. We analysed gene to gene interactions among 23 polymorphic loci using the multifactor-dimensionality reduction (MDR) method, which has been shown to be effective for detecting and characterising gene to gene interactions in case-control studies with relatively small samples. RESULTS: The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor gamma ( PPARgamma) gene. This interaction showed the maximum consistency and minimum prediction error among all gene to gene interaction models evaluated. Moreover, the combination of the UCP2 55 Ala/Val heterozygote and the PPARgamma 161 C/C homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio: 0.51, 95% CI: 0.34 to 0.77, p=0.0016). CONCLUSIONS/INTERPRETATION: Using the MDR method, we showed a two-locus interaction between the UCP2 and PPARgamma genes among 23 loci in the candidate genes of Type 2 diabetes. The determination of such genotype combinations contributing to Type 2 diabetes mellitus could provide a new tool for identifying high-risk individuals.

Aged↗