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Biomedical subjects

S H Kang

Publications and source records attributed to S H Kang.

At least 73 records · Page 4Linked to original sources
PubMed1998

Synthesis and biological activity of bis(pivaloyloxymethyl) ester of 2'-azido-2'-deoxyuridine 5'-monophosphate.

Bis(pivaloyloxymethyl) ester of 2'-azido-2'-deoxyuridine 5'-monophosphate was prepared as a prodrug to generate 2'-azido-2'-deoxyuridine 5'-diphosphate inside the cell. A synthetic route utilizing stannyl phosphate was adopted in the preparation. The prodrug was evaluated for cell growth inhibition against a variety of tumor cell lines along with 2'-azido-2'-deoxyuridine and 2'-azido-2'-deoxycytidine.

Animals↗
PubMed1998

Rates and independent correlates of Pap smear testing among Korean-American women.

OBJECTIVES: This study reports population estimates of Pap smear testing among Korean-American women and evaluates correlates of testing. METHODS: Korean Americans in 2 California counties were surveyed by telephone. Frequencies were age-adjusted to the 1990 census to produce population estimates of testing. Logistic regression models were used to evaluate independent correlates of testing RESULTS: Only 50% of the Korean-American women surveyed had a Pap test in the previous 2 years. The strongest independent correlate was having had a regular check-up in the previous 2 years (odds ratio 7.2, 95% confidence interval 4.2, 12.1). CONCLUSIONS: Rates of Pap testing among Korean-American women are well below national objectives. Collaboration and community-sensitive research are essential to collect data and design programs to improve the health of ethnic minority communities.

Asian↗
PubMed1998

Impaired flow-mediated vasodilation of epicardial coronary artery in vasospastic angina.

To evaluate whether the flow-mediated vasodilation and coronary flow reserve are impaired or not in patients with vasospastic angina (VA), we measured the changes of epicardial coronary artery diameter and flow reserve in spasm related-left anterior descending coronary artery (LAD). The flow mediated-response of epicardial coronary arteries in 15 VA were compared with 15 controls. Using quantitative coronary angiography, we measured the diameter of proximal (pLAD) and middle segment (mid-LAD) of LAD under baseline conditions, during increased blood flow after distal adenosine injection and after proximal administration of nitroglycerin. An increased fraction of average peak velocity after injection of adenosine was similar in both groups [control 340 (mean)+/-24 (SEM)%; VA 330+/-19%]. Flow-mediated vasodilation was preserved in all controls (pLAD 13.1+/-1.4%; mid-LAD 15.8+/-2.5%) but it was significantly impaired in patients with VA (pLAD -1.0+/-1.8%; mid-LAD 0.1+/-3.5%). The vasodilator response to nitroglycerin was comparable in controls (pLAD 25.8+/-2.8%; mid-LAD 27.2+/-2.8%) and VA (pLAD 26.2+/-5.2%; mid-LAD 26.7+/-3.5%). Coronary flow reserve is preserved in patients with VA. However, the flow-mediated response of spasm related-epicardial coronary artery is impaired. This may play an important role in the pathogenesis of coronary artery spasm.

Adult↗
PubMed1998

Korean Nationwide Surveillance of Antimicrobial Resistance of bacteria in 1997.

Antimicrobial-resistant bacteria are known to be prevalent in tertiary-care hospitals in Korea. Twenty hospitals participated to this surveillance to determine the nationwide prevalence of resistance bacteria in 1997. Seven per cent and 26% of Escherichia coli and Klebsiella pneumoniae were resistant to 3rd-generation cephalosporin. Increased resistance rates, 19% of Acinetobacter baumannii to ampicillin/sulbactam, and 17% of Pseudomonas aeruginoa to imipenem, were noted. The resistance rate to fluoroquinolone rose to 24% in E. coli, 56% in A. baumannii and 42% in P. aeruginosa. Mean resistance rates were similar in all hospital groups: about 17% of P. aeruginosa to imipenem, 50% of Haemophilus influenzae to ampicillin, 70% of Staphylococcus aureus to methicillin, and 70% of pneumococci to penicillin. In conclusion, nosocomial pathogens and problem resistant organisms are prevalent in smaller hospitals too, indicating nosocomial spread is a significant cause of the increasing prevalence of resistant bacteria in Korea.

Bacterial Physiological Phenomena↗
PubMed1997

Alterations of p16INK4A and p15INK4B genes in gastric carcinomas.

BACKGROUND: It has been suggested that cyclin-dependent kinase inhibitors (CDKIs), including p16 and p15, are tumor suppressor genes. Alterations of CDKIs have been found in most types of cancer. However, little is known about the status of p16 and p15 genes, including methylation of the promoter region, in gastric carcinoma. METHODS: Thirty-six primary gastric tumors and 9 gastric carcinoma cell lines were examined for alterations of the p16 and p15 genes. Deletion of the p16 and p15 genes was assessed by Southern blot analysis, expression by Northern blot analysis, and mutation by polymerase chain reaction-single strand conformation polymorphism followed by direct sequencing. The methylation status of the 5' CpG island of the p16 gene was evaluated using methylation-sensitive restriction enzymes, and reversal of the transcriptional block of the p16 gene was determined by Northern blot analysis after treatment with 5-aza-2'-deoxycytidine. RESULTS: Homozygous deletions of the p16 and 15 genes from 2 of 9 gastric carcinoma cell lines were found. In contrast, no deletions were detected in 36 primary gastric tumors, and one primary tumor showed rearrangements of the p16 and p15 genes. Two gastric carcinoma cell lines showed a point mutation and an insertional mutation of the p16 gene, respectively; however, no point mutations were noted for the p16 and p15 genes in any of the primary gastric tumors. Constitutive levels of p16 mRNA expression in gastric carcinoma cell lines were quite heterogeneous; four gastric carcinoma cell lines had no detectable p16 mRNA and 6 gastric carcinoma cell lines had negligible expression of p15 mRNA. Of 10 primary gastric tumors, only 1 tumor expressed p16 mRNA. Furthermore, abnormal DNA methylation patterns of the p16 gene were found in 2 gastric carcinoma cell lines through the use of methylation-sensitive restriction enzymes. These cell lines lacked expression of p16 mRNA without deletions of the p16 gene. These transcriptional blocks were reversed by treatment with 5-aza-2'-deoxycytidine. CONCLUSIONS: Deletions or mutations of the p16 and p15 genes are uncommon in primary gastric carcinomas. However, defective mRNA transcription, sometimes by aberrant DNA methylation, might be one of the pathways of inactivation of the p16 gene that leads to the development of gastric carcinoma.

Adenocarcinoma↗
PubMed1997

Establishment and characterization of human gastric carcinoma cell lines.

We report 8 newly established gastric-carcinoma cell lines (SNU-216, 484, 520, 601, 620, 638, 668, 719) from Korean patients. Morphologic study was carried out using light and electron microscopes. CEA, alpha FP, and CA 19-9 and TPA in supernatant and in cell lysate were measured by radioimmunoassay. p53 and c-Ki-ras gene mutations were screened and confirmed by sequencing. The cell lines, derived from tumors with moderate differentiation, grew as a diffuse monolayer, and those from tumors with poor differentiation and minimal desmoplasia grew exclusively as non-adherent. Out of the 8 gastric-cancer cell lines, 5 had detectable levels of CEA both in supernatant and in cell lysate; there was no expression or secretion of alpha FP in these cells; 4 cell lines showed high levels of CA 19-9 in cell pellets. All cell lines except SNU-484 had high concentrations of TPA both in cell lysate and in supernatants. p53 mutation was found in 6 cell lines (75%): 2 (SNU-216 and SNU-668) had mutations in exon 6, and other 3 in exon 8. The c-Ki-ras mutation was found in 2 cell lines (25%), SNU-601 and SNU-668. The former showed GGT-to-GAT transition mutation at codon 12, while the latter showed CAA-to-AAA transversion mutation at codon 61. DNA profiles using restriction endonuclease HinfI and polymorphic DNA probes ChdTC-15 and ChdTC-114 showed different unique patterns; which suggests that these cell lines are unique and not cross-contaminated. We believe that the newly characterized gastric-cancer cell lines presented in this paper will provide a useful in vitro model for studies related to human gastric cancer.

Adult↗
PubMed1997

Distribution of ABO genotypes and allele frequencies in a Korean population.

The genotypes of the ABO blood group system were investigated in Korean living in Kangwon-Do area by PCR-RFLP analysis of the seven polymorphic nucleotide positions 261, 467, 526, 646, 703, 796 and 803 of the cDNA from A1 transferase. In 253 unrelated Korean individuals, 15 genotypes were found and the allele frequencies of A(Pro), A(Leu), B, O(T) and O(A) were 0.022, 0.209, 0.209, 0.360 and 0.200, respectively, with no deviation from Hardy-Weinberg expectations (chi 2 = 2.145, d.f. = 6, 0.90 < p < 0.95). As for the distribution of allele frequencies, a significant difference was noticed between the Korean and a Japanese (chi 2 = 30.87, d.f. = 4, p < 0.001) and a German (chi 2 = 127.76, d.f. = 4, p < 0.001) populations.

ABO Blood-Group System↗
PubMed1997

Simultaneous determination of methylparaben, propylparaben and thimerosal by high-performance liquid chromatography and electrochemical detection.

A reversed-phase high-performance liquid chromatographic method using amperometric detection has been developed for the analysis of methylparaben, propylparaben and thimerosal. The liquid chromatographic separation of the three preservatives was made possible on a C18-bonded silica column with a mixed solvent consisting of methanol and aqueous 0.02 M phosphoric acid (59:41, v/v). A potential value of +1.25 V versus Ag/AgCl was chosen for simultaneous analysis. The limits of detection were 1, 2 and 5 ng for a 20 microliters injection volume of methylparaben, propylparaben and thimerosal, respectively. The analysis time of less than 20 min in this study was found to be applicable for routine analysis of these compounds in pharmaceutical products.

Chromatography, High Pressure Liquid↗
PubMed1997

Determination of homocysteine and other thiols in human plasma by capillary electrophoresis.

A new capillary electrophoresis (CE) assay for thiols in human plasma, including homocysteine, which is an indicator of several clinical states has been developed. The thiols were derivatized quantitatively at 50 degrees C, pH 8.0 with a fluorogenic reagent, ADB-F (4-aminosulfonyl-7-fluoro-2,1,3-benzoxadiazole), which is about 30 times faster compared to the other fluorogenic reagent, SBD-F (ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate). The separation of ABD-thiols was performed in a 50 mM sodium phosphate buffer (pH 2.1) using a bare fused silica capillary (27 cm x 50 microns i.d.) at 25 degrees C. With the electric field of 560 V cm-1, the time needed for the separation of homocysteine, glutathione and cysteine was less than 8 min. A filter-type ultraviolet detector and a 512-channel diode-array detector (DAD) were employed for ABD-thiol analysis. DAD was used to confirm the ABD-thiol peaks. The limits of detection (S/N = 3) for homocysteine, glutathione, and cysteine were 0.5, 1 and 2 microM at 220 nm, respectively.

Electrophoresis, Capillary↗
PubMed1997

Cellular delivery of nucleoside diphosphates: a prodrug approach.

PURPOSE: This study is concerned with cellular delivery/generation of 2'-azido-2'-deoxyuridine and -deoxycytidine diphosphate (N3UDP or N3CDP), potent inhibitors of ribonucleotide reductase. It characterizes the phosphorylation steps involved in the conversion of 2'-azido-2'-deoxyuridine (N3Urd) and 2'-azido-2'-deoxycytidine (N3Cyd) to the corresponding diphosphates and explores a prodrug approach in cellular delivery of the inhibitor which circumvents the requirement of deoxynucleoside kinases. METHODS: Cell growth of CHO and 3T6 cells of known deoxycytidine kinase level was determined in the presence of N3Urd and N3Cyd. Activity of ribonucleotide reductase was determined in the presence of the azidonucleosides as well as their mono- or di-phosphates in a Tween 80-containing permeabilizing buffer. A prodrug of 5'-monophosphate of N3Urd was prepared and its biological activity was evaluated with CHO cells as well as with cells transfected with deoxycytidine kinase. RESULTS: N3Urd failed to inhibit the growth of both cell lines, while N3Cyd was active against 3T6 cells and moderately active against CHO cells. These results correlate with the deoxycytidine kinase levels found in the cells. Importance of the kinase was further established with the finding that the nucleoside analogs were inactive as reductase inhibitors in a permeabilized cell assay system while their mono- and di-phosphates were equally active. The prodrug was active in cell growth inhibition regardless of the deoxycytidine kinase level. CONCLUSIONS: The azidonucleosides become potent inhibitors of the reductase by two sequential phosphorylation steps. The present study indicates that the first step to monophosphate is rate-limiting, justifying a prodrug approach with the monophosphate.

Animals↗
PubMed1996

Sequence requirements of ATF2 and CREB binding to the human T-cell leukemia virus type 1 LTR R region.

We have identified crucial transcription factor contact sites within the distal portion of the HTLV-1 LTR R region. Single base substitutions within this region greatly reduce formation of a complex which we previously described as a 70-kDa nuclear protein interacting with a CREB-like protein. Comparison of published sequences of HTLV-1 isolates obtained from scattered geographic locations revealed that clustered mutations in an 8-base segment near the U5 junction do, in fact, occur naturally. A single base substitution corresponding to a common naturally occurring mutation was introduced into the R region of an HTLV-1-LTR Cat construct. This resulted in derepression of the promoter in a cell line expressing high levels of the R region binding complex when compared to the wild-type LTR promoter. Affinity purification and electrophoretic mobility super-shift analysis identified a dominant 70-kDa DNA binding protein as ATF-2. Phosphorylated ATF-2 apparently interacts with CREB to form this downstream complex.

Activating Transcription Factor 2↗
PubMed1996

Binding and functional effects of transcriptional factor Sp1 on the murine interleukin-6 promotor.

The NF-kappaB and NF-IL6 elements have previously been shown to play an important role in regulation of both the mouse and human interleukin-6 gene. Between these two elements lies a G/C-rich sequence, which contains three repeats of the element CCACC, protein binding to which has not been previously characterized. In this study we demonstrate that the transcription factor Sp1 binds to these repeats and plays an important role in basal and in inducible expression of the murine interleukin-6 gene.

3T3 Cells↗
PubMed1996

A case of combined gastrojejunal and gastrocolic fistula secondary to gastric cancer.

A rare case of gastric cancer associated with gastrojejunal and gastrocolic fistula is presented. A 56-year-old man who had been diagnosed with advanced gastric cancer(Borrmann's type III) 5 months previously was admitted due to watery diarrhea and frequent vomiting for 2 weeks. Fluoroscopic examination was visualized two abnormal passage of contrast medium from the stomach, one to the colon, and the other to the jejunum. Gastrofiberscopy revealed that the tumor on the great curvature of the body appeared to penetrate into the colon, while the other one on the antrum directly invaded into the jejunum. The patient was treated conservatively with total parenteral nutrition and pain control.

Colonic Diseases↗
PubMed1996

Long-term gene expression from autonomously replicating vectors in mammalian cells.

We tested the longevity of gene expression provided by autonomously replicating vectors. The vectors contain segments of human genomic DNA that provide efficient replication initiation and sequences derived from Epstein-Barr virus that provide nuclear retention. In order to monitor gene expression, the vectors also carry an expression cassette containing the chloramphenicol acetyl transferase gene. Replicating and control vectors were transfected into rapidly dividing human 293 cells, and gene expression and DNA retention were monitored. Gene expression decreased rapidly from a control vector lacking replication and retention functions, reaching near background levels by 10 days. Vectors having both replication and retention showed greatly prolonged gene expression, with vector DNA still detectable after 2 months. Autonomously replicating vectors also prolonged gene expression in rodent cells, in human lung epithelial cells, and in slowly dividing cell cultures. These results demonstrate the utility of this autonomous replication system for long-term retention and expression of introduced genes in mammalian cells. Such vectors could be useful for gene therapy, in combination with any of several methods for introduction of DNA.

Animals↗
PubMed1995

Ribozyme-mediated RNA degradation in nuclei suspension.

Ribozymes containing 2'-fluoro- and 2'-amino-modified pyrimidine nucleosides in combination with terminal phosphorothioate linkages were targeted against HTLV-I tax RNA. In order to examine the activity of such chemically modified ribozymes in the nuclear environment, they were incubated with nuclei of a Tax-transformed mouse fibroblast cell line. Ribozyme cleavage of tax RNA was analyzed by the RNase protection assay. Comparison of the cleavage of tax RNA isolated nuclei with that of tax RNA present in nuclei suspension revealed a 30 times more efficient cleavage of the latter one. Pre-treatment with proteinase K and SDS abolished the enhancement of the ribozyme-mediated RNA cleavage. Catalytically inactive ribozymes did not yield any cleavage products. These results demonstrate an augmenting effect of nuclear proteins on the ribozyme-mediated RNA cleavage.

Animals↗
PubMed1995

Application of antisense technology to therapeutics.

Antisense oligonucleotides inhibit gene expression by binding in a sequence-specific manner to an RNA target. Modern nucleotide chemistry has enabled the synthesis of chemically modified oligonucleotides that are highly resistant to nuclease degradation. Among other applications, these agents are currently being evaluated as potential antiviral and anticancer drugs. However, several unsolved problems remain. Poor efficiency of delivery to cells, tissue toxicity and antisense-independent biological effects of oligonucleotides currently limit the widespread application of antisense oligonucleotides to human disease. This article reviews some of the applications of antisense oligonucleotides and discusses problems associated with these applications.

Animals↗