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Biomedical subjects

Y W Kim

Publications and source records attributed to Y W Kim.

At least 37 records · Page 2Linked to original sources
PubMed2003

Prediction of lymph nodes metastasis by sentinel node biopsy in gastric cancer.

AIM: The application of sentinel node (SN) biopsy in gastric cancer remains controversial. In this study, detection rate and predictive values of SN biopsy were determined to evaluate its feasibility in gastric cancer. Various clinicopathologic features were also analysed to determine the factors affecting the detection rate and predictive values. METHODS: Seventy-one gastric adenocarcinoma patients without serosal invasion and distant metastasis, were studied. One percent isosulfan blue stained nodes were defined as SNs, and standard gastrectomy with D2 lymphadenectomy was performed. All lymph nodes were studied by hematoxylin and eosin staining. RESULTS: SNs were identified in 65 of 71 patients and average number of SNs per patient was 2.5 (range 1-8). Among the 65 patients with SNs, metastatic SNs were found in 11 and the remaining 54 were free of metastasis. In eight of the 11 patients with metastasis of the SNs, metastases were also identified in non-SNs. CONCLUSIONS: SN biopsy is feasible in early stage gastric cancer. However, complementary procedures may be needed to improve the detection rate and predictive values. SNs biopsy results should be treated with caution in male patients and for tumours at the upper part of stomach due to the low detection rate.

Adenocarcinoma↗
PubMed2002

Lack of association between glutathione S-transferase P1 polymorphism and COPD in Koreans.

The fact that only 10-20% of chronic heavy cigarette smokers develop symptomatic COPD and correlations of pulmonary function among twins and families suggests the presence of genetic susceptibility in the development of COPD. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase (GST). The purpose of this study was to determine whether polymorphism of GSTP1 gene is linked to a genetic susceptibility to COPD. The hypothesis we tested here was that the polymorphism supposed to decrease GSTP1 activity would be the genetic risk for the development of COPD. Using PCR followed by restriction fragment length polymorphism (PCR-RFLP), genotypes of Ile105Val polymorphism in exon 5 of glutathione S-transferase P1 (GSTP1) gene were determined in 89 patients with COPD and 94 healthy smoking control subjects at the Seoul National University Hospital. Although the frequency of homozygous wild allele in exon 5 of GSTP1 gene in patients with COPD was higher than that observed in healthy controls (71% vs. 61%), the difference was not considered statistically significant. Neither the heterozygous nor homozygous mutant allele differed in frequency between the two groups. In conclusion, the genetic polymorphisms of exon 5 of GSTP1 gene may not be associated with development of COPD in Koreans.

Adult↗
PubMed2002

Hydraulic properties and leachate level analysis of Kimpo metropolitan landfill, Korea.

Hydraulic properties of waste and cover soil from Kimpo Metropolitan Landfill were experimentally measured by laboratory tests. The degree of compaction was changed to identify the effect on hydraulic conductivity, field capacity, and permanent wilting point. Properties were utilized in developing a reliable numerical tool for leachate analysis. HELP, a simulation model for hydrologic evaluation of landfill performance, was adopted for that purpose. For calibration, results from simulation using the parameter values measured by laboratory tests were compared against the field data. The model was applied to predict the leachate level change according to the degree of compaction and cover soil thickness variation. It was found that the increase in the degree of compaction for intermediate cover soil and waste results in the decrease of field capacity and hydraulic conductivity, hence, the increase of leachate level. The effect of cover layer thickness on the leachate level was minor. Based on the findings from laboratory and numerical experiments, a guideline for reclamation practice was recommended.

Calibration↗
PubMed2002

The response to iron deprivation in Saccharomyces cerevisiae: expression of siderophore-based systems of iron uptake.

The budding yeast Saccharomyces cerevisiae responds to growth in limiting amounts of iron by activating the transcription factor Aft1p and expressing a set of genes that ameliorate the effects of iron deprivation. Analysis of iron-regulated gene expression using cDNA microarrays has revealed the set of genes controlled by iron and Aft1p. Many of these genes are involved in the uptake of siderophore-bound iron from the environment. One family of genes, FIT1, FIT2 and FIT3, codes for mannoproteins that are incorporated into the cell wall via glycosylphosphatidylinositol anchors. These genes are involved in the retention of siderophore-iron in the cell wall. Siderophore-bound iron can be taken up into the cell via two genetically separable systems. One system requires the reduction and release of the iron from the siderophore prior to uptake by members of the Fre family of plasma-membrane metalloreductases. Following reduction and release from the siderophore, the iron is then taken up via the high-affinity ferrous transport system. A set of transporters that specifically recognizes siderophore-iron chelates is also expressed under conditions of iron deprivation. These transporters, encoded by ARN1, ARN2/TAF1, ARN3/SIT1 and ARN4/ENB1, facilitate the uptake of both hydroxamate- and catecholate-type siderophores. The Arn transporters are expressed in intracellular vesicles that correspond to the endosomal compartment, which suggests that intracellular trafficking of the siderophore and/or its transporter may be important for uptake.

Biological Transport↗
PubMed2002

Two cases of steakhouse syndrome associated with nutcracker esophagus.

The most common type of esophageal food-related foreign body is the meat bolus, which is frequently associated with underlying esophageal stenosis. Herein, we report two cases of meat bolus impaction associated with nutcracker esophagus. In the first case, the 63-year-old male patient had chest discomfort and swallowing difficulty after ingestion of butcher's meat. In the second case, the 55-year-old male patient had complained of swallowing difficulty after ingestion of chicken. In both cases, no pathologic findings were observed endoscopically after removal of the esophageal meat bolus. We performed esophageal manometry, which showed very high amplitudes of esophageal pressure in the mid- and distal esophagus. These findings were consistent with nutcracker esophagus. These cases show that esophageal motility disorder may be the cause of esophageal foreign body impaction, and esophageal manometry should be performed for evaluation of the cause of foreign body, especially in an endoscopically normal patient.

Deglutition Disorders↗
PubMed2001

Modulation of the multisubstrate specificity of Thermus maltogenic amylase by truncation of the N-terminal domain and by a salt-induced shift of the monomer/dimer equilibrium.

The relation between the quaternary structure and the substrate specificity of Thermus maltogenic amylase (ThMA) has been investigated. Sedimentation diffusion equilibrium ultracentrifugation and gel filtration analyses, in combination with the crystal structure determined recently, have demonstrated that ThMA existed in a monomer/dimer equilibrium. The truncation of ThMA by removing the N-terminal domain, which is composed of 124 amino acid residues, resulted in the complete monomerization of the enzyme (ThMADelta124) accompanied by a drastic decrease in the activity for beta-cyclodextrin (beta-CD) and a relatively smaller reduction of the activity for starch. Despite the overall low activity of ThMADelta124, the activity was higher toward starch than beta-CD, and the ratio of the specific activities toward these substrates was approximately 100 fold higher than that of wild-type ThMA. Furthermore, the addition of KCl to wild-type ThMA shifted the monomer/dimer equilibrium toward the monomer. In the presence of 1.0 M KCl, the relative activity of ThMA toward beta-CD decreased to 74%, while that for soluble starch increased to 194% compared to the activities in the absence of KCl. Thus, the ThMA monomer and dimer are both inferred to be enzymatically active but with a somewhat different substrate preference. Kinetic parameters of the wild-type and truncated enzymes also are in accordance with the changes in their specific activities. We thus provide evidence in support of a model, which shows that the relative multisubstrate specificity of ThMA is influenced by the monomer/dimer equilibrium of the enzyme.

Amino Acid Sequence↗
PubMed2001

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers.

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

Antibodies, Monoclonal↗
PubMed2001

Protein kinase C modulates telomerase activity in human cervical cancer cells.

Telomerase, a ribonucleoprotein reverse transcriptase that extends telomeres of eukaryotic chromosomes is repressed in normal somatic cells but is activated during development and neoplasia. The regulation mechanism of telomerase activity in cancer cells is not clearly known. In this report, a possible affect of PKC on telomerase activity was examined using HeLa and CUMC-6 cervical cancer cell lines. Exposure of cells to PKC inhibitor, bisindolylmaleimide I and Gö6976, and high levels of PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA) resulted in the inhibition of PKC activity in both cells. Telomerase activities were also inhibited by bisindolyl-maleimide I and Gö6976, respectively, in a time-dependent manner. As PKC activity changes in TPA-treated cervical cancer cells, telomerase activities were increased at low dose of TPA and decreased at high dose. The expression levels of human telomerase subunits, human telomerase RNA (hTR) were not influenced by PKC modulating drugs. In contrast, the expression of full-length human telomerase reverse transcriptase (hTERT) was decreased after exposure to bisindolylmaleimide I and Gö6976 in a time-dependent manner. hTERT expression was not affected by low dose of TPA. In contrast, high dose of TPA inhibited hTERT expression level. But the expression patterns of beta-deletion transcript of hTERT after 72 h of treatment with PKC inhibitors or high dose of TPA exposure were not discernable as compared with those of full-length hTERT transcripts to PKC modulating drugs. These results suggest that PKC-modulating drugs altered telomerase activities by affecting full-length hTERT expression profile in human cervical cancers.

Alternative Splicing↗
PubMed2001

Characterization of a novel laccase produced by the wood-rotting fungus Phellinus ribis.

The white-rot fungus Phellinus ribis produced a single form of laccase, which was purified to apparent electrophoretic homogeneity from cultures induced with 2,5-xylidine. This protein was a dimer, consisting of two subunits of 76 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Carbohydrate analysis revealed that the enzyme contained about 28% carbohydrate content. The laccase appeared to be different from other known laccases by the UV-visible absorption spectrum analysis. One enzyme molecule contained one copper, one manganese, and two zinc atoms. The laccase showed optimal activity at pH 4.0-6.0, 5.0, and 6.0 with 2,6-dimethoxyphenol, ABTS [2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)], and syringaldazine, respectively. The enzyme preferably oxidized dimethoxyphenol and aromatic amine compounds. The stability of the laccase was low at acidic pH, whereas it showed high stability at neutral pH and mild temperature. The N-terminal amino acid sequence revealed a very low homology with other microbial laccases. With some substrates, the addition of manganese and H2O2 resulted in a remarkable increase in the oxidation rate. Without an appropriate phenolic substrate, the enzyme could not oxidize Mn(II) in the presence of H2O2 or pyrophosphate.

Amino Acid Sequence↗
PubMed2001

An adenovirus expressing mutant p27 showed more potent antitumor effects than adenovirus-p27 wild type.

The main inhibitory action of p27, a cyclin-dependent kinase inhibitor (CDKI), arises from its binding with the cyclin E/cyclin-dependent kinase 2 (Cdk2) complex that results in G(1)-S arrest. Degradation of p27 is mediated by phosphorylation of Thr-187 of p27, which follows ubiquitination. In this study, we generated two adenoviruses expressing wild-type p27 (ad-p27wt) and mutant p27 (ad-p27mt), with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC), which was produced with the belief that mutant p27 would bind cyclin E/CDK2 more stably and show more potent antitumor effects. Ad-p27wt and ad-p27mt expressed p27 proteins that were indistinguishable by anti-p27 antibody. A pulse chase experiment showed that p27mt was more resistant to degradation than p27wt. In human lung cancer cell lines, ad-p27mt showed stronger growth inhibition than ad-p27wt. Both types of ad-p27 induced G(1)-S arrest and apoptosis; however, ad-p27mt induced stronger G(1)-S arrest and apoptosis. Intratumoral injection of ad-p27mt induced partial regression of established tumors and inhibited the growth of human lung cancer xenografts more strongly than ad-p27wt. From these results, we conclude that ad-p27mt has the potential to become a novel and powerful gene therapy tool.

Adenoviridae↗
PubMed2001

Synthesis and biological evaluation of novel A-ring modified hexacyclic camptothecin analogues.

Eleven A-ring modified hexacyclic analogues of camptothecin (CPT) containing a 1,4-oxazine ring were synthesized from 10-hydroxycamptothecin (11a) and 7-ethyl-10-hydroxycamptothecin (3) (SN-38) in four to five steps and were subjected to the biological tests such as cytotoxicity, topoisomerase I (Topo I) inhibitory activity, acetylcholinesterase (AChE) inhibition, and stability in human plasma. Four compounds 15a, 15b, 16a, and 16c were about 2-fold more potent than topotecan and as potent as CPT toward human cancer cell lines A549, H128, WiDr, MKN45, SK-OV-3, and SK-BR-3 in vitro, even though the most active compound 15b was slightly less potent than SN-38. The potency of Topo I inhibition of these compounds showed relatively good correlation with their cytotoxicity. Most of the compounds exhibited AChE inhibitory activity weaker (9 +/- 2 to 20 +/- 3%) than CPT (23 +/- 5%) or topotecan (20 +/- 4%) and similar to SN-38 (13 +/- 2%), indicating that they might have little effect on causing early diarrhea. The stability of lactone forms of these compounds in human plasma seemed to be much higher than that of CPT and similar to that of topotecan but lower than that of SN-38. Among the new hexacyclic CPT analogues, compound 15b showed higher antitumor activity against human tumor xenograft, WiDr, in nude mice compared to that of SN-38. The most promising compound 15b has been selected for further development.

Animals↗
PubMed2001

Membrane curvature induced by polymer adsorption.

The phenomena resulting from interaction between polymers and membranes pose important problems for biological applications. Based on a scaling theory, we investigate the spontaneous curvature of a membrane induced by either flexible or semiflexible chain adsorption. Irrespective of chain stiffness, a weakly adsorbed polymer induces the membrane to bend away (to have a positive curvature) from the polymer mostly due to increase of the conformational entropy compared with that for a flat surface. On the other hand, a strongly adsorbed polymer induces the membrane to bend toward the polymer mostly due to decrease in the interaction energy, leading to a possibility of encapsulation of polymer by the membrane.

Adsorption↗
PubMed2001

Increased expression of cFLIP(L) in colonic adenocarcinoma.

During tumour progression, cancer cells use diverse mechanisms to escape from apoptosis-inducing stimuli, which may include receptor internalization, inhibition of signal pathways, and regulation of specific sets of genes. Substantial numbers of colon cancer cells have been observed to express Fas/Fas ligand, but are resistant to Fas-mediated apoptosis, suggesting that colonic tumours might develop specific mechanisms to overcome Fas-mediated apoptosis. Recently, cellular FLICE-like inhibitory protein (cFLIP) has been identified as an endogenous inhibitor of Fas- or other receptor-mediated apoptosis and its altered high expression has a suspected association with tumour development or progression. In an effort to investigate the prevalence of cFLIP(L) alterations in colon carcinomas and their possible implications for the progression of colon cancers, cFLIP(L) expression was analysed in adenocarcinomas and adenomatous polyps of colon, with matched normal tissues, at RNA and protein levels, by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. cFLIP(L) transcripts were constitutively expressed in colon cancers and expression levels were significantly higher in carcinomas than in normal tissues (p<0.05). Overexpression of cFLIP(L) protein was found exclusively in carcinoma cells in all matched sets analysed and approximately three-fold induction was detected in cancer cells (p<0.05). The expression of cFLIP(L) protein was not significantly altered in adenomatous polyps compared with normal tissues. Taken together, these results strongly suggest that abnormal overexpression of cFLIP(L) is a frequent event in colon carcinomas and might contribute to in vivo tumour transformation.

Adenocarcinoma↗
PubMed2001

Malignant mixed müllerian tumor of the ovary: imaging findings.

OBJECTIVE: We describe the imaging findings of malignant mixed müllerian tumor (MMMT) of the ovary, which have not previously been reported. MATERIALS AND METHODS: We experienced 13 cases of ovarian MMMT in eight patients. All patients underwent surgical resection and the MMMTs were confirmed pathologically. US (n = 8), CT (n = 8), and MRI (n = 1) examinations were performed before operation. Imaging features were analyzed retrospectively for bilaterality, tumor solidity (cystic or solid), size, and contrast enhancement of the tumor on CT and MRI. Presence of ascites and other evidence of peritoneal seeding, adjacent organ invasion, distant metastasis, and surgical staging were also evaluated. RESULTS: There were bilateral ovarian MMMTs in five patients and unilateral MMMTs in three patients. Two of the MMMTs were multiseptated cystic, and 11 were mixed (solid and cystic). The diameter of the largest dimension was less than 5 cm in one case, 5-10 cm in two cases, and larger than 10 cm in 10 cases. Dense homogeneous contrast enhancement of the solid component was seen in 11 mixed masses. Ascites were found in all patients. Other evidence of peritoneal seeding and direct invasion into adjacent organ such as the uterus or sigmoid colon was seen in five patients each. Pleural metastasis was present in one patient. Surgical stages were FIGO classification IIIb and IV in one patient each, and IIIc in six patients. CONCLUSION: Ovarian MMMTs usually present as aggressive, bilateral, large, solid and cystic tumors, combined with ascites, frequent peritoneal seeding, and adjacent organ invasion.

Adult↗
PubMed2001

Clinical significance of urinary vascular endothelial growth factor and microvessel density in patients with renal cell carcinoma.

OBJECTIVES: To investigate the urinary vascular endothelial growth factor (VEGF) levels from patients with renal cell carcinoma (RCC). Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. VEGF is thought to exert potent angiogenic activity. METHODS: Urine samples were obtained before radical nephrectomy from 27 patients with RCC and 10 control subjects with no evidence of cancer or inflammatory disease. VEGF was measured by enzyme-linked immunosorbent assay in the urine and corrected according to the 24-hour urine concentration of creatinine. The microvessel density was measured by immunohistochemical staining with CD31 monoclonal antibody. Nuclear morphometry was performed by photomicroscopy. RESULTS: The corrected urinary VEGF levels in patients with RCC were much higher than those in the normal control group (P = 0.039) and were more elevated in patients with higher stages of RCC (Stages III and IV versus Stages I and II; P = 0.024). A tendency was also noted for the VEGF levels to be higher according to cell grade. However, no statistical correlation was found between the corrected urinary VEGF and age, sex, tumor size, cell type, microvessel density, platelet count, or hemoglobin. The nuclear area was higher with more advanced-stage tumors (P = 0.043) and tended to increase according to the tumor cell grade. CONCLUSIONS: The results of this study indicate that urinary VEGF levels are increased in patients with RCC. However, they may not reflect the underlying angiogenic activity, and it may be that other angiogenic factors play a more prominent role.

Analysis of Variance↗
PubMed2001

Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues.

New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Identification of a signal that distinguishes between the chloroplast outer envelope membrane and the endomembrane system in vivo.

Certain small outer envelope membrane proteins of chloroplasts are encoded by the nuclear genome without a cleavable N-terminal transit peptide. We investigated in vivo the targeting mechanism of AtOEP7, an Arabidopsis homolog of the small outer envelope membrane protein. AtOEP7 was expressed as a fusion protein with the green fluorescent protein (GFP) either transiently in protoplasts or stably in transgenic plants. In either case, fluorescence microscopy of transformed cells and protein gel blot analysis of fractionated proteins confirmed that the AtOEP7:GFP fusion protein was targeted to the chloroplast outer envelope membrane. In vivo targeting experiments revealed that two regions, the transmembrane domain (TMD) and its C-terminal neighboring seven-amino acid region, were necessary and sufficient for targeting to the chloroplast outer membrane. Substitution of aspartic acid or lysine residues with glycine residues or scrambling of the amino acid sequence of the seven-amino acid region caused mistargeting to the plasma membrane. Although the amino acid sequence of the TMD is not important for targeting, amino acid residues with large side chains inhibited targeting to the chloroplasts and resulted in the formation of large aggregates in the protoplasts. In addition, introduction of a proline residue within the TMD resulted in inhibition of targeting. Finally, a fusion protein, AtOEP7:NLS:GFP, was targeted efficiently to the chloroplast envelope membranes despite the presence of a nuclear localization signal. On the basis of these results, we conclude that the seven-amino acid region and the TMD are determinants for targeting to the chloroplast outer envelope membrane. The seven-amino acid region plays a critical role in AtOEP7 evading the endomembrane system and entering the chloroplast pathway, and the TMD plays critical roles in migration to the chloroplasts and/or subsequent insertion into the membrane.

Amino Acid Sequence↗