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Biomedical subjects

S H Kang

Publications and source records attributed to S H Kang.

At least 19 recordsLinked to original sources
PubMed2001

Nuclear antisense effects of neutral, anionic and cationic oligonucleotide analogs.

The antisense activity of oligomers with 2'-O-methyl (2'-O-Me) phosphorothioate, 2'-O-methoxyethyl (2'-O-MOE) phosphorothioate, morpholino and peptide nucleic acid (PNA) backbones was investigated using a splicing assay in which the modified oligonucleotides blocked aberrant and restored correct splicing of modified enhanced green fluorescent protein (EGFP) precursor to mRNA (pre-mRNA), generating properly translated EGFP. In this approach, antisense activity of each oligomer was directly proportional to up-regulation of the EGFP reporter. This provided a positive, quantitative readout for sequence-specific antisense effects of the oligomers in the nuclei of individual cells. Nuclear localization of fluorescent labeled oligomers confirmed validity of the functional assay. The results showed that the free uptake and the antisense efficacy of neutral morpholino derivatives and cationic PNA were much higher than that of negatively charged 2'-O-Me and 2'-O-MOE congeners. The effects of the PNA oligomers were observed to be dependent on the number of L-lysine (Lys) residues at the C-terminus. The experiments suggest that the PNA containing Lys was taken up by a mechanism similar to that of cell-penetrating homeodomain proteins and that the Lys tail enhanced intracellular accumulation of PNA oligomer without affecting its ability to reach and hybridize to the target sequence.

Anions↗
PubMed2001

Sample size calculations for clustered binary data.

In this paper we propose a sample size calculation method for testing on a binomial proportion when binary observations are dependent within clusters. In estimating the binomial proportion in clustered binary data, two weighting systems have been popular: equal weights to clusters and equal weights to units within clusters. When the number of units varies cluster by cluster, performance of these two weighting systems depends on the extent of correlation among units within each cluster. In addition to them, we will also use an optimal weighting method that minimizes the variance of the estimator. A sample size formula is derived for each of the estimators with different weighting schemes. We apply these methods to the sample size calculation for the sensitivity of a periodontal diagnostic test. Simulation studies are conducted to evaluate a finite sample performance of the three estimators. We also assess the influence of misspecified input parameter values on the calculated sample size. The optimal estimator requires equal or smaller sample sizes and is more robust to the misspecification of an input parameter than those assigning equal weights to units or clusters.

Bacteroides Infections↗
PubMed2001

Tests for 2 x K contingency tables with clustered ordered categorical data.

Ordered categorical data summarized in a 2 x K table usually consist of two-sample multinomial or K-sample binomial observations. In analysing these data, we usually assign scores to the K columns and perform a testing for the equality of two multinomial distributions in the former case and no trend among K binomial proportions in the latter case. Among the most popular score tests are the Wilcoxon rank sum test and the Armitage's linear trend test. In this paper we extend the score tests to be used for clustered data under diverse study designs. Our methods do not require correct specification of the dependence structure within clusters. The proposed tests are based on the asymptotic normality for large number of clusters and are a generalization of the standard tests used for independent data. Simulation studies are conducted to investigate the finite-sample performance of the new methods. The proposed methods are applied to real-life data.

Amoxicillin↗
PubMed2001

Real-time dynamics of single-DNA molecules undergoing adsorption and desorption at liquid-solid interfaces.

The conformational dynamics and adsorption/desorption behavior of individual lambda-DNA molecules at liquid-solid interfaces were monitored by imaging within the evanescent field layer using total internal reflection fluorescence microscopy. At a fused-silica surface, molecular conformation and adsorption behavior were found to depend on both pH and buffer composition. A histogram of individual lambda-DNA adsorption durations measured by hydrodynamically flowing molecules along the interface exhibited asymmetry nearly identical to that of the corresponding elution peaks found in capillary liquid chromatography and capillary electrophoresis. The accessibility of the surface to the molecules, which is proportional to the capillary surface area-to-volume ratio, can be correlated with the capacity factor and the relative adsorption factor. At a C18 surface, the dynamics of individual DNA molecules changed with the addition of organic solvent as well as with pH. Hydrophobic interaction rather than electrostatic interaction was the major driving force for adsorption of individual DNA molecules.

Adsorption↗
PubMed2001

In vivo pharmacokinetics of pyribenzoxim in rats.

Pyribenzoxim, benzophenone O-[2,6-bis(4,6-dimethoxypyrimidin-2-yloxy)benzoyl]oxime, is a new post-emergence herbicide providing broad-spectrum weed control in rice fields. [14C]Pyribenzoxim was used to study the pharmacokinetics of the compound after oral administration of a dose of 1000 mg kg-1 to male Sprague-Dawley rats. The material balance ranged from 97.3 to 99.7% of the administered dose and urinary and fecal recovery accounted for 97.1%, with the majority of radioactivity recovered in feces (88.6%) by 168 h after treatment. Elimination as volatile products or as carbon dioxide was negligible. The following values were obtained for the compound in the blood: AUC0-168 h, 28,400 micrograms equiv hg-1; Tmax, 12 h; Cmax, 372 micrograms equiv g-1; half-life, 53 h. Radioactivity in tissue decreased from 96.1% of applied radiocarbon at 6 h to 0.4% at 168 h and the highest concentration of radioactivity among the tissues was observed in liver while the lowest residues were found in brain. The elimination half-lives of radioactivity from tissues was in the range of 7 to 77 h and Tmax values of 12, 24 and 12 h were observed for blood, liver and kidney, respectively. Except for that in the digestive tract, the tissue-to-blood ratio (TBR) was highest in the liver.

Administration, Oral↗
PubMed2001

Echocardiographic evaluation of left-ventricular diastolic function in patients with chronic pulmonary hypertension.

Different patterns of left-ventricular (LV) diastolic dysfunction were reported in patients with pulmonary hypertension (PHT). There are no data regarding the relationship between the severity of PHT and LV diastolic dysfunction. In order to determine the severity of PHT at which LV diastolic dysfunction occurs and to identify its pattern, we studied by Doppler echocardiography 120 patients with PHT (57 with severe PHT and 63 with mild or moderate PHT) and compared them with 75 normal controls. Systolic pulmonary artery pressure (SPAP) was measured by tricuspid regurgitant jet method and the usual transmitral LV diastolic indices were recorded. LV diastolic dysfunction of impaired relaxation type is most commonly seen in patients with severe PHT. No differences were observed between patients with mild and moderate PHT regarding LV diastolic function. A SPAP > or =60 mm Hg is needed to induce changes in the LV diastolic filling pattern.

Adult↗
PubMed2001

Interrogation of the tricuspid annulus by Doppler tissue imaging in patients with chronic pulmonary hypertension: implications for the assessment of right-ventricular systolic and diastolic function.

BACKGROUND: Chronic pulmonary hypertension (CPHT) has a great impact on both right-ventricular (RV) systolic and diastolic properties and the assessment of those properties is not always feasible by traditional echocardiographic examination. Doppler tissue imaging (DTI) interrogation of the tricuspid annulus (TA) identifies the pattern of TA motion (TAM) and can help to assess RV function when other methods are not feasible. AIMS: To determine RV systolic and diastolic function in patients with CPHT using DTI parameters of the TA. METHODS: Eighty-seven patients with CPHT and 90 normal controls were studied. DTI parameters were measured including early diastolic, late diastolic and systolic velocities and time velocity integrals (TVI) of the TAM at both its lateral and medial aspect. RESULTS: Early diastolic and systolic velocities, the ratio of early to late diastolic velocities and TVI of TAM at both lateral and medial aspects were significantly decreased in patients with CPHT compared to controls. No significant differences were seen in late diastolic velocities and TVI in both groups. Systolic velocity of the TAM at both its lateral and medial aspects significantly correlated with RV systolic function as measured by fractional RV area change. CONCLUSIONS: DTI of the TAM can be used to assess RV systolic and diastolic properties in patients with CPHT.

Aged↗
PubMed2001

Individual differences in urinary cotinine levels in Japanese smokers: relation to genetic polymorphism of drug-metabolizing enzymes.

Urinary cotinine, one of the main metabolites of nicotine, has been widely used as a biomarker for assessment of direct or passive exposure to cigarette smoke. However, there is wide variation of the cotinine level among smokers who smoke the same number of cigarettes. To use urinary cotinine as a proper exposure-biomarker for cigarette smoke, interindividual variations of cotinine formation must be considered. Therefore, we studied the effects of genetic polymorphisms in drug metabolic enzymes on urinary cotinine levels among 190 male Japanese smokers (ages 19-66 years; mean, 40.6 years). Genetic polymorphisms in cytochrome P-450s (CYP1A1, CYP2A6, CYP2E1), and aldehyde dehydrogenase 2 (ALDH2) were determined by analyzing DNA isolated from peripheral blood. Cotinine in morning spot urine was analyzed by high-performance liquid chromatography. Lifestyle, i.e., smoking, alcohol consumption, and intake of coffee or tea, was examined using a questionnaire. The number of cigarettes smoked and CYP2A6 polymorphism were significantly associated with the urinary cotinine level. Especially, the urinary cotinine levels was drastically lower in CYP2A6-deleted homozygous (CYP2A6*4/*4) subjects than in CYP2A6*1 allele-positive subjects. The polymorphism in the CYP2E1 5'-flanking region was related to the urinary cotinine level in intermediate smokers (who smoke 11-20 cigarettes/day; P < 0.01). Polymorphisms in CYP1A1 or ALDH2, and consumption of alcohol, coffee, or tea were not associated with the urinary cotinine level.

Adult↗
PubMed2001

Association of HLA class II genes with systemic sclerosis in Koreans.

OBJECTIVE: To investigate HLA class II associations with systemic sclerosis (SSc) in Koreans according to anti-topoisomerase I (anti-topo I), anti-centromere antibody (ACA), and anti-U1 ribonucleoprotein (RNP) status. METHODS: HLA class II alleles (DRB1, DRB5, DQB1) were determined by DNA typing in 200 healthy control subjects and 74 patients with SSc: 35 anti-topo I positive, 3 ACA positive, and 19 anti-U1 RNP positive; among them were 34 diffuse and 40 limited subtypes, and 16 overlap syndrome. RESULTS: Anti-topo I positive SSc was strongly associated with DRB1*1502 compared with both controls (23% vs 5%; Pcorr = 0.003) and anti-topo I negative patients (23% vs 3%; p = 0.009); our study confirms observations in Japanese. HLA-DR 67FLEDR71, especially 38V-67FLEDR71 sequence (carried on DRB5*0102 in linkage disequilibrium with DRB1*1502, DRB1*0802, DRBI*1101), showed the strongest association with anti-topo I response (46% vs 16% in controls; Pcorr = 0.001), and 38L-67FLEDR71 group alleles were not associated with anti-topo I response. Anti-topo I response was not significantly associated with HLA-DQB1 alleles in Koreans. There were only 3 ACA positive patients, and all patients had DRB1*1501 and DQB1*0602 as heterozygotes. Anti-U1 RNP occurred at a high frequency (63%) among patients with overlap syndrome, and was not associated with HLA-DR or DQ genes. Among anti-topo I negative patients, diffuse and limited subtypes of SSc were significantly associated with DRB1*0803 (47% vs 15% in controls; Pcorr < 0.05) and DRB1*1501 (50% vs 17% in controls; Pcorr < 0.01), respectively. These HLA associations have not been reported in other ethnic groups and possible associations with certain autoantibody subsets remain to be confirmed. CONCLUSION: HLA-DR gene has a primary association with anti-topo I response, and HLA-DR 38V-67FLEDR71 group alleles including DRB5*0102 (in linkage disequilibrium with DRB1*1502) show the strongest association with anti-topo I response in Korean patients with SSc.

Adult↗
PubMed2001

The maize CRINKLY4 receptor kinase controls a cell-autonomous differentiation response.

The maize (Zea mays) CRINKLY4 (cr4) gene encodes a receptor-like kinase that controls a variety of cell differentiation responses, particularly in the leaf epidermis and in the aleurone of the endosperm. In situ hybridization indicated that the cr4 transcript is present throughout the shoot apical meristem and young leaf primordia. A genetic mosaic analysis was conducted to test whether CR4 signal transduction directly regulated the cellular processes associated with differentiation or whether differentiation was controlled through the production of a secondary signal. Genetic mosaics were created using gamma-rays to induce chromosome breakage in a cr4/Cr4+ heterozygote. The mutant cr4 allele was marked with the albino mutation, Oy-700. Breakage and loss of the chromosome arm carrying the wild-type alleles created a sector of albino, cr4 mutant tissue in an otherwise normal leaf. Analysis of such sectors indicated that cr4 functions cell autonomously to regulate cell morphogenesis, implying that CR4 signal transduction regulates cell differentiation through strictly intracellular functions and not the production of secondary intercellular signals. However, several sectors altered cell patterning in wild-type tissue adjacent to the sectors, suggesting that cr4 mutant cells are defective in the production of other lateral signals.

Anthocyanins↗
PubMed2000

An efficient cell-free protein synthesis system using periplasmic phosphatase-removed S30 extract.

An efficient cell-free translation system was developed by removal of phosphatase localized in the periplasmic space, which hampers the translation reaction by hydrolyzing ATP. S30 extract was prepared from the spheroplast of Escherichia coli, and as much as 40% of ATP-hydrolysis activity of phosphatases could be easily removed by the spheroplast formation. The reaction period of translation using phosphatase-removed S30 extract could be prolonged and protein synthesis was enhanced by more than 30%.

Cell-Free System↗
PubMed2000

An approximate unconditional test of non-inferiority between two proportions.

This paper investigates an approximate unconditional test for non-inferiority between two independent binomial proportions. The P-value of the approximate unconditional test is evaluated using the maximum likelihood estimate of the nuisance parameter. In this paper, we clarify some differences in defining the rejection regions between the approximate unconditional and conventional conditional or unconditional exact test. We compare the approximate unconditional test with the asymptotic test and unconditional exact test by Chan (Statistics in Medicine, 17, 1403-1413, 1998) with respect to the type I error and power. In general, the type I errors and powers are in the decreasing order of the asymptotic, approximate unconditional and unconditional exact tests. In many cases, the type I errors are above the nominal level from the asymptotic test, and are below the nominal level from the unconditional exact test. In summary, when the non-inferiority test is formulated in terms of the difference between two proportions, the approximate unconditional test is the most desirable, because it is easier to implement and generally more powerful than the unconditional exact test and its size rarely exceeds the nominal size. However, when a test between two proportions is formulated in terms of the ratio of two proportions, such as a test of efficacy, more caution should be made in selecting a test procedure. The performance of the tests depends on the sample size and the range of plausible values of the nuisance parameter. Published in 2000 by John Wiley & Sons, Ltd.

Child↗
PubMed2000

High-throughput comprehensive peptide mapping of proteins by multiplexed capillary electrophoresis.

A novel multimodal method for peptide mapping of proteins by multiplexed capillary electrophoresis (CE) is presented. By combining charge to size separations in four different channels and micellar electrokinetic chromatography for hydrophobicity-based separations in two different channels in a 96-capillary array, peptide fragments of digested proteins were readily resolved and showed unique fingerprints. Each capillary spanned several diodes in a photodiode array (PDA) for absorption measurement. The 96 capillaries were monitored simultaneously at 214 nm by a single PDA element with 1,024 diodes, and analysis was completed within 45 min. This demonstrates that it is possible to rapidly screen biotechnological products as well as to efficiently optimize separation conditions in CE by a combinatorial approach.

Amino Acid Sequence↗
PubMed2000

Methylation of specific CpG sites in the promoter region could significantly down-regulate p16(INK4a) expression in gastric adenocarcinoma.

Silencing of p16(INK4a) by methylation of the CpG islands in the promoter region has been found to be an alternative mechanism of inactivation in several tumors. However, in gastric carcinoma, the relationship between methylation status and the transcriptional silencing of the p16 gene remains to be clarified. In this study, we investigated whether methylation of a few specific CpG sites in the promoter region could significantly down-regulate p16 activity in the tumorigenesis of gastric carcinoma. By Southern analysis and bisulfite-modified genomic sequencing of 9 gastric-carcinoma cell lines, we found that the 5 cell lines (55.5%) not expressing p16 mRNA had methylated CpG sites at the promoter region of p16. In addition, we analyzed the p16-protein expression of 28 primary gastric carcinomas and their normal counterparts by immunohistochemical staining (IHC) on paraffin sections. Loss of p16 expression was detected in 6 cases (22%). In 5 out of these 6 (83%), the actual p16 gene was inactivated by de novo methylation of the promoter sites. Taken together, these results suggest a strong correlation between de novo methylation of a few specific CpG sites and transcriptional silencing of the p16 gene in gastric carcinoma.

Adenocarcinoma↗
PubMed2000

On-column derivatization for the analysis of homocysteine and other thiols by capillary electrophoresis with laser-induced fluorescence detection.

On-column derivatization and capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection has been developed for the fully automated assay of homocysteine and other thiols. The unique feature of this CE technique comes from the direct injection of a sample including homocysteine, enabling the derivatization with 4-aminosulfonyl-7-fluoro-2,1,3-benzoxadizole (ABD-F) to be accomplished in the capillary. After the derivatization for 10 min at 50 degrees C, the homocysteine was analyzed within 7 min under an applied electric field of 333 V cm(-1). The detection limit obtained for homocysteine with on-column LIF detection was 5.0 nM, as compared to 2.5 nM with pre-column LIF detection. The method is a very simple, fast, and practical approach for the fully automated assay of homocysteine and other thiols contained in low-volume and low-concentration samples.

Electrophoresis, Capillary↗
PubMed2000

Transcriptional inactivation of the tissue inhibitor of metalloproteinase-3 gene by dna hypermethylation of the 5'-CpG island in human gastric cancer cell lines.

The tissue inhibitor of metalloproteinase-3 (TIMP-3), a recently cloned member of TIMP gene family, has been implicated in the negative regulation of tumor cell invasion and tumor growth. Down-regulation of this gene has been shown to occur in a mouse carcinogenesis model, suggesting that it might play a role in the tumor progression of some cancers. In this study, we used human gastric cancer cell lines to investigate whether TIMP-3 gene expression is suppressed in human gastric cancer. We examined whether aberrant DNA methylation of the 5'-CpG island of the TIMP-3 gene is involved in this cancer. Nine of 10 human gastric cancer cell lines completely lost TIMP-3 gene expression compared with normal samples. Southern blot analysis and bisulfite genomic sequencing revealed aberrant hypermethylation near the transcription-start site of the TIMP-3 gene in all cell lines lacking TIMP-3 expression. Treatment of these cell lines with the demethylating agent 5-aza-2'-deoxycytidine restored TIMP-3 gene expression. Our results suggest that the TIMP-3 gene is another early target of tumor-associated aberrant DNA methylation in human gastric carcinogenesis. Consequently, genetic silencing of TIMP-3 may lead to a more malignant and invasive phenotype in these cancer cells.

Animals↗