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Biomedical subjects

Y B Kim

Publications and source records attributed to Y B Kim.

At least 37 records · Page 2Linked to original sources
PubMed2002

Occurrence of zearalenone in Korean barley and corn foods.

The presence of zearalenone (ZEN) in Korean foods such as barley, barley-based foods, corn, corn-based foods, fruits and vegetables was investigated by direct competitive enzyme-linked immunosorbent assay (dcELISA) and the liquid chromatography (LC) method. A total of 164 samples was collected from Seoul, Korea, in 1998 and 1999 including 30 barley, 32 barley-based foods, 18 corn, 47 corn-based foods, 19 dried red pepper, nine dried jujube, and nine dried persimmon. Average recoveries of ZEN from barley and corn by dcELISA were 138 and 145%, and by LC were 91 and 83% respectively at spiking levels of 5-500 ngg(-1). The detection limit for ZEN was 3 ng g(-1) by dcELISA and 4 ngg(-1) by LC. From 164 samples analysed, ZEN was found by dcELISA in 35 samples (21%) with a mean level of 30 ng g(-1). Barley-based foods had the highest incidence of ZEN (38%) followed by barley (33%), corn-based foods (26%) and corn (22%). No ZEN was detected in any red pepper, jujube or persimmon samples. A high degree of correlation (r2 = 0.86) was observed between the 35 positive samples detected by dcELISA and 31 samples by LC.

Chromatography, Liquid↗
PubMed2002

Natural co-occurrence of aflatoxin B1, fumonisin B1 and ochratoxin A in barley and corn foods from Korea.

A survey for aflatoxin B1 (AFB1), fumonisin B1 and ochratoxin A (OTA) was conducted on 127 samples that included 30 food-grade barley, 32 barley foods, 18 food-grade corn and 47 corn foods, randomly collected during 1998-99 in Seoul, Korea. The presence of mycotoxins was analysed by direct competitive enzyme-linked immunosorbent assay (ELISA), and most of the positive samples from ELISA were confirmed using high-performance liquid chromatography (HPLC). Recoveries of AFB1 and OTA spiked at 10 ng g(-1) and FB1 spiked at 50 ng g(-1) were 106, 87 and 105% by ELISA, whereas those by HPLC were 80, 79 and 84%, respectively. Detection limits by ELISA for AFB1, FB1 and OTA were 1, 5 and 5 ng g(-1), and those by HPLC were 0.6, 35 and 1 ng g(-1). Naturally occurring AFB1, FB1 and OTA were found in 4/32 (12%), 2/32(6%) and 4/32 (12%) samples of barley foods with an average of 26, 16 and 9 ng g(-1), respectively. AFB1 and FB1 in corn foods were detected in 4/47 (8%) and 9/47 (19%) samples with the average being 20 and 74 ng g(-1), while no OTA was found in any corn foods samples. No AFB1, FB1 or OTA was detected in any of food-grade barley and corn samples. This is the first report on the natural co-occurrence of AFB1 and FB1 in barley and corn foods as well as on surveillance of OTA in Korea.

Aflatoxin B1↗
PubMed2001

Development of a safe and rapid neutralization assay using murine leukemia virus pseudotyped with HIV type 1 envelope glycoprotein lacking the cytoplasmic domain.

Neutralizing antibody (NAb) is a critical component of an immune system that can potentially provide sterilizing protection against human immunodeficiency virus type 1 (HIV-1). Therefore, an in vitro assay that can rapidly, safely, and accurately evaluate the NAb response vaccine candidates elicit, especially against a large number of HIV-1 variants, would be highly valuable. It has been demonstrated that HIV-1 envelope glycoprotein lacking the cytoplasmic domain can pseudotype murine leukemia virus encoding the beta-galactosidase gene and that this pseudovirus can specifically infect CD4(+) cells (Schnierle BS, Stitz J, Bosch V, et al.: Proc Natl Acad Sci USA 1997;94:8640-8645). Because the pseudovirus is not biohazardous and because the infection can be quantitatively determined within 2 days, we examined the feasibility of using the pseudovirus for high-throughput neutralization assays for HIV-1. We have generated viruses pseudotyped with gp140 of six different HIV-1 isolates (LAI, RF, Bal, AD8, 89.6, and DH12). All six pseudoviruses were infectious and exhibited expected coreceptor usage phenotype in HOS-CD4 cells expressing either CCR5 or CXCR4. More importantly, the neutralization sensitivity profile of these pseudoviruses was virtually identical to that observed from more conventional neutralization assays using either HIV-1 or SHIV. All pseudoviruses could be neutralized by broadly reactive human monoclonal antibody IgG1 b12. Our results indicate that the pseudoviruses are ideal for high-throughput evaluation of immune sera for their capacity to broadly neutralize a large number of HIV-1 isolates.

Base Sequence↗
PubMed2001

Apoptosis and proliferation in hepatocarcinogenesis related to cirrhosis.

BACKGROUND: Dysplastic nodules (DNs) recently have been identified as preneoplastic lesions of hepatocellular carcinoma (HCC). To test an alternative hypothesis regarding DN development, in which we have suggested that DNs develop as an infiltrating clonal expansion in advance of, or parallel to cirrhosis, the authors investigated the rates of apoptosis and proliferation in human hepatocarcinogenesis. METHODS: The authors performed terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and proliferation cell nuclear antigen (PCNA) staining in 11 low-grade DNs, 8 high-grade DNs including 3 cases with HCC subnodules, 10 small HCCs, and 29 cases of surrounding cirrhotic nodules. Hepatocellular carcinoma subnodules were present in three cases of high DNs. They determined TUNEL-labeling indices (LIs) and PCNA-LIs as the percentage of positive hepatocyte nuclei per 500 randomly counted cells. RESULTS: TUNEL-LIs (mean +/- standard deviation) were 0.8 +/- 0.82 in cirrhotic nodules, 1.0 +/- 0.98 in low-grade DNs, 3.0 +/- 4.33 in high-grade DNs, 8.7 +/- 7.71 in HCC subnodules of high-grade DNs, and 3.2 +/- 3.58 in small HCCs. The peak values of apoptotic activity were higher in high-grade DNs and HCCs than in low-grade DNs and cirrhotic nodules. Each case of low-grade DN showed a low to medium level of apoptotic activity when compared with those of the four surrounding cirrhotic nodules. The PCNA-LIs were 2.6 +/- 1.35 in cirrhotic nodules, 4.5 +/- 2.31 in low-grade DNs, 15.3 +/- 10.50 in high-grade DNs, 25.4 +/- 5.25 in HCC subnodules of high-grade DNs, and 34.9 +/- 15.70 in small HCCs. The peak values gradually increased, although only HCC showed significantly elevated proliferation activity. The differences of PCNA-LIs and TUNEL-LIs, measured in each case, were 1.7 +/- 1.89 in cirrhotic nodules, 3.6 +/- 2.43 in low-grade DNs, 7.9 +/- 5.69 in high-grade DNs, 16.2 +/- 2.87 in HCC subnodules of high-grade DNs, 28.2 +/- 13.97 in small HCCs. At all stages of hepatocarcinogenesis, the rates of cell proliferation were higher than apoptosis, allowing a preferential net gain of (pre)neoplastic cells, and it was significantly increased in small HCCs. In regenerative cirrhotic nodules, 14% (4 cases) showed higher rates of apoptosis than proliferation. CONCLUSIONS: The regulation/dysregulation of apoptosis of (pre)neoplastic cells as well as of proliferation may play an important role in the process of hepatocarcinogenesis.

Adult↗
PubMed2001

Methylation of O(6)-methylguanine-DNA methyltransferase gene is associated significantly with K-ras mutation, lymph node invasion, tumor staging, and disease free survival in patients with gastric carcinoma.

BACKGROUND: O(6)-methylguanine-DNA methyltransferase (MGMT) can remove O(6)alkylG DNA adducts. If they are not removed, then the adducts mispair with T during DNA replication, resulting in G-to-A mutation. Interrelations between MGMT gene inactivation by promoter methylation, K-ras mutation, and clinicopathologic features in patients with gastric carcinoma were studied. METHODS: Surgically removed tumor tissues from 79 patients were analyzed with MGMT methylation by genomic DNA modification and methylation specific polymerase chain reaction analysis, K-ras mutation by mutant allele specific amplification, TNM classification according to the International Union Against Cancer system, and MGMT protein expression by immunohistochemistry. RESULTS: MGMT-promoter methylation was found in 18 of 79 tumors. Among those 18 tumors, K-ras mutations were found in 33% and 11% of tumors at codons 12 and 13, respectively, corresponding to 20 times and 7 times greater rates of mutation compared with unmethylated tumors. MGMT methylation was associated significantly with lymph node invasion (P < 0.01), tumor stage (P < 0.03) and 5-year disease free survival (P < 0.02). MGMT protein expression was detected in intestinal metaplasia and adenocarcinoma samples, whereas no expression was detected in normal foveolar cells. CONCLUSIONS: MGMT-promoter methylation in patients with gastric carcinoma was associated significantly with point mutations of K-ras at codons 12 and 13, lymph node invasion, tumor stage, and disease free survival. These associations indicate a significant role of MGMT methylation during gastric carcinogenesis.

Adenocarcinoma↗
PubMed2001

Biosynthesis of polyhydroxyalkanoate copolyester containing cyclohexyl groups by Pseudomonas oleovorans.

Production of polyhydroxyalkanoates (PHAs) substituted with cyclohexyl groups by Pseudomonas oleovorans grown with 4-cyclohexylbutyric acid (4-CHB) and its mixtures with nonanoic acid (NA) was investigated. Addition of NA to medium gave rise to an increase in the total concentration of 3-hydroxy-4-cyclohexylbutyrate repeating unit in the PHAs, indicating that the bioconversion rate of 4-CHB to polyester was significantly improved by the cometabolic effect. Increasing the proportion of NA from 1.0 to 7.5 mM at a concentration of 10 mM total carbon substrate also accelerated the uptake speed of 4-CHB by the organism and resulted in an increase of the ratio of 3-hydroxynonanoate to 3-hydroxyheptanoate from 1.28 to 2.05. Differential scanning calorimetric analysis of the PHAs bearing the corresponding functional groups showed one melting transition and one glass transition temperature varying according to the composition. These results indicated that random copolyesters were obtained from the carbon substrates used in this study.

Butyric Acid↗
PubMed2001

Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett's esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants.

Oxidative damage has long been related to mucosal damages of gastrointestinal tracts and their ensuing carcinogenesis. In spite of treatment with anti-secretory medications for reflux esophagitis, considerable portions of patient did not achieve the complete mucosal healings or suffered from sustaining symptoms or development of dread complication like Barrett's esophagus, suggesting other damaging factors or impaired mucosal resistance are also involved in their pathogenesis. The present study was designed either to evaluate the oxidative stress as the major pathogenic factor of reflux esophagitis or to find out the usefulness of antioxidant in the treatment of reflux esophagitis and the prevention of development of Barrett's esophagus. Acute or chronic reflux esophagitis was induced through either narrowing the third portion of duodenal lumen or performing myotomy of lower esophageal sphincter in rats, respectively. DA-9601, a new phytopharmaceutical possessing antioxidative properties, significantly attenuated the gross and histopathologic scores of acute reflux esophagitis in a dose-dependent manner compared to those treated with ranitidine alone. Only scattered erosions were observed in antioxidant pre-treated group, but acid suppression by ranitidine was not so effective in decreasing the severity of reflux esophagitis. Significantly increased amounts of malondialdehyde (MDA), increased NF-kappa B activations, and depletions of reduced glutathione (GSH) were observed in experimentally induced reflux esophagitis, but DA-9601 pre-treatment attenuated the decrement of mucosal GSH levels and decreased MDA formations significantly. DA-9601 treatment showed significant reductions in the activation of NF-kappa B transcription factor. DA-9601 significantly decreased the proliferating cell nuclear antigen-labeling index (PCNA-LI) of esophagus (P<0.05) in chronic reflux esophagitis model and prevented the development of Barrett's esophagus. In conclusion, reflux esophagitis provoked considerable levels of oxidative stress in the esophageal mucosa. Antioxidant treatment seems to be the first line therapeutics in the prevention or treatment of reflux esophagitis. Moreover, antioxidant possibly played the chemopreventive role through preventing the development of Barrett's esophagus.

Acute Disease↗
PubMed2001

Restriction fragment length dimorphism-PCR method for the detection of extended-spectrum beta-lactamases unrelated to TEM- and SHV-types.

The diagnostic ability of the restriction fragment length dimorphism-polymerase chain reaction (RFLD-PCR) method was evaluated. Seven primer pairs, newly designed from 44 beta-lactamase genes encoding extended-spectrum beta-lactamases not related to TEM- and SHV-types, were used to differentiate OXA-2, FOX-3, CMY-3, IMP-1, and IMI-1 beta-lactamases. The RFLD-PCR was carried out successfully, and these genes were differentiated by the sizes of their PCR products and by the difference in restriction fragment length when each amplicon was digested with a unique restriction enzyme. This discriminatory detection of the genes was confirmed by sequencing the PCR products.

Bacterial Proteins↗
PubMed2001

Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes.

beta cells sense glucose through its metabolism and the resulting increase in ATP, which subsequently stimulates insulin secretion. Uncoupling protein-2 (UCP2) mediates mitochondrial proton leak, decreasing ATP production. In the present study, we assessed UCP2's role in regulating insulin secretion. UCP2-deficient mice had higher islet ATP levels and increased glucose-stimulated insulin secretion, establishing that UCP2 negatively regulates insulin secretion. Of pathophysiologic significance, UCP2 was markedly upregulated in islets of ob/ob mice, a model of obesity-induced diabetes. Importantly, ob/ob mice lacking UCP2 had restored first-phase insulin secretion, increased serum insulin levels, and greatly decreased levels of glycemia. These results establish UCP2 as a key component of beta cell glucose sensing, and as a critical link between obesity, beta cell dysfunction, and type 2 diabetes.

Adenosine Triphosphate↗
PubMed2001

The significance of granzyme B expression in patients with angiocentric lymphoma of the head and neck.

BACKGROUND: The objectives of this study were to establish a correlation between granzyme B expression and the clinicopathologic characteristics of patients with angiocentric lymphomas of the head and neck and to determine whether the expression of granzyme B had any influence on the treatment outcomes of such patients. METHODS: Fifty-seven patients with angiocentric lymphoma of the head and neck who were treated between 1987 and 1996 were divided into two groups according to whether their tumors were immunoreactive for granzyme B: the granzyme B negative group (n = 22 patients) and the granzyme B positive group (n = 35 patients). The clinicopathologic features, immunohistochemical findings, patterns of disease failure, and survival data for the granzyme B positive group were compared with those for the granzyme B negative group. RESULTS: Greater than 60% of patients with angiocentric lymphoma of the head and neck were shown to have granzyme B positive tumors. All tumors that expressed granzyme B also consistently coexpressed CD56, indicating that they probably are the neoplastic equivalent of either natural killer (NK) cells or activated cytotoxic T cells. Although there were no significant differences in histopathologic features or expression of CD45RO and polyclonal CD3-epsilon between the groups, the Epstein-Barr virus genomes were detected more frequently in the granzyme B positive group compared with the granzyme B negative group. Despite a similar rate of complete remission after initial treatment, the locoregional recurrence rate of patients in the granzyme B positive group was much higher compared with patients in the granzyme B negative group. In addition, compared with patients in the granzyme B negative group, patients in the granzyme B positive group also had an increased risk of systemic disease recurrence and a decreased overall survival rate. CONCLUSIONS: The data indicate that the cytotoxic granule-associated protein, granzyme B, may be used as an additional marker for identifying NK/T-cell lymphoma and as a prognostic indicator for risk assessment in patients with angiocentric lymphoma of the head and neck.

Adult↗
PubMed2001

Human mdm2 mediates multiple mono-ubiquitination of p53 by a mechanism requiring enzyme isomerization.

The mdm2 gene product is an important regulator of p53 function and stability. mdm2 is an E3 ubiquitin ligase for p53 and the RING finger domain of mdm2 is critical for ligase activity. Ubiquitin (Ub) conjugation is a general targeting modification and poly-ubiquitin chains specifically target proteins to the proteasome for degradation. In this report, we show that the multistep cascade of mdm2-mediated p53 ubiquitination can be reduced to three purified recombinant proteins: ubiquitin-conjugated E2, mdm2, and p53. This simplification allows enzymatic analysis of the isolated ligase reaction. The simplified reaction recapitulates the ubiquitination of p53 observed with individual components and the p53-Ub((n)) is qualitatively similar to p53-Ub((n)) detected in lactacystin-treated cells. Surprisingly, we find that p53 is modified with multiple mono-ubiquitin moieties as opposed to a poly-ubiquitin chain. Finally, kinetic analysis indicates the transfer reaction proceeds either through a modified Ping Pong mechanism involving requisite enzyme isomerization steps, or through a Rapid Equilibrium Random Bi Bi mechanism involving very large anti-cooperative interactions between the two substrate binding pockets on the enzyme, mediated through allosteric changes in enzyme structure.

Ethylmaleimide↗
PubMed2001

Isolation and characterization of cultured human periodental ligament fibroblast-specific cDNAs.

The molecular mechanisms that control the function of periodontal ligament (PDL) fibroblasts remain unclear. We speculated that the character of differentiating PDL fibroblasts is defined by the altered expansion of specific genes not found in neighboring gingival fibroblasts in the periodontium. To expand this set, subtractive hybridization was applied between cultured human PDL and gingival fibroblasts to identify genes differentially expressed in PDL. Consequently five candidate clones, PDLs (periodontal ligament specific) 5, -17, -22, -25, and -31 were identified and characterized by homology search, Northern analysis, and in situ hybridization. Although the mRNAs of these clones were expressed by bone marrow cells and rarely by gingival fibroblasts, the highest expression was detected in the PDL cells, which were uniformly distributed throughout the whole PDL. Amongst the five candidate clones, we focused on PDLs17, because it is a hypothetical protein whose biological function has not been reported yet in the database. Polyclonal antiserum raised against PDLs17 peptide was made, and stained the PDL fibroblasts, osteoblast-like cells and stromal cells in the bone marrow, but not gingival fibroblasts. The results suggest that clones, PDLs5, -17, -22, -25, and -31 may be used as PDL fibroblast-specific markers, and that PDLs17 could act as an important factor in the differentiation process of PDL fibroblasts.

Blotting, Northern↗
PubMed2001

Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance.

Previous reports indicate that the expression and/or activity of the protein-tyrosine phosphatase (PTP) LAR are increased in insulin-responsive tissues of obese, insulin-resistant humans and rodents, but it is not known whether these alterations contribute to the pathogenesis of insulin resistance. To address this question, we generated transgenic mice that overexpress human LAR, specifically in muscle, to levels comparable to those reported in insulin-resistant humans. In LAR-transgenic mice, fasting plasma insulin was increased 2.5-fold compared with wild-type controls, whereas fasting glucose was normal. Whole-body glucose disposal and glucose uptake into muscle in vivo were reduced by 39-50%. Insulin injection resulted in normal tyrosyl phosphorylation of the insulin receptor and insulin receptor substrate 1 (IRS-1) in muscle of transgenic mice. However, phosphorylation of IRS-2 was reduced by 62%, PI3' kinase activity associated with phosphotyrosine, IRS-1, or IRS-2 was reduced by 34-57%, and association of p85alpha with both IRS proteins was reduced by 39-52%. Thus, overexpression of LAR in muscle causes whole-body insulin resistance, most likely due to dephosphorylation of specific regulatory phosphotyrosines on IRS proteins. Our data suggest that increased expression and/or activity of LAR or related PTPs in insulin target tissues of obese humans may contribute to the pathogenesis of insulin resistance.

Animals↗
PubMed2001

Oxidative damages are critical in pathogenesis of reflux esophagitis: implication of antioxidants in its treatment.

BACKGROUND: The facts that the severity of reflux esophagitis cannot be accurately predicted on the basis of acid exposure and acid suppression treatment is not enough for the complete healing, suggested that other damaging factors might be involved in pathogenesis of reflux esophagitis. AIMS: The present study was designed to evaluate the oxidative stress as the major pathogenic factor of reflux esophagitis and the importance of antioxidant in treatment of reflux esophagitis. MATERIALS AND METHODS: Reflux esophagitis was induced by the insertion of small caliber ring (3 mm in diameter) into the duodenum 1 cm distal to the ligament of Treitz in rats. RESULTS: DA-9601, a novel antioxidant substance, attenuated the gross esophagitis significantly compared to that treated with ranitidine, histamine-2 receptor antagonist (H2-RA), in a dose-dependent manner. Severe, hemorrhagic, and longitudinal ulcerations were developed in H2-RA pretreated group, whereas mildly scattered erosions were observed in antioxidant-pretreated group. Significantly increased amounts of malondialdehyde (MDA), increased NF-kappaB activation, and the mucosal depletion of reduced glutathione (GSH) were observed in the esophagus of reflux esophagitis. H2-RA treatment didn't affect the levels of GSH and MDA, whereas DA-9601 attenuated the decrement of the GSH levels and significantly decreased lipid peroxides in the esophagus. Antioxidants treatment showed significant reductions in the activation of NF-kappaB, inflammation-associated transcription factor, especially p50 component in accordance with significant higher levels of NF-kappaB repressor, IkappaBalpha expression. CONCLUSION: Oxygen-derived free radicals seem to be one of the important mediators in generation of reflux esophagitis, which suggests that the combination of antioxidant and anti-secretory medications will be ideal and more beneficial in the prevention and treatment of reflux esophagitis than currently prescribed antisecretory treatment alone.

Animals↗
PubMed2001

Molecular cloning and expression pattern of porcine myeloid DAP12-associating lectin-1.

DAP12 is an ITAM-bearing membrane protein that is associated with activating receptors in natural killer cells, granulocytes, macrophages, and monocytes. Myeloid DAP12-associating lectin-1 (MDL-1) is a type II membrane protein that associates with DAP12. In this study, we report the molecular cloning of two isoforms of porcine MDL-1 cDNA from pulmonary alveolar macrophages. The porcine MDL-1 short form has 165 amino acids and 70% sequence identity with the mouse MDL-1 short form. The long form has 20 more amino acids in the stalk region and 71% sequence identity with human MDL-1 and 67% with the mouse MDL-1 long form. Porcine MDL-1 contains a conserved lysine in the transmembrane domain. There are six putative N-linked glycosylation sites in the MDL-1 long form. MDL-1 transcripts were detected exclusively in macrophages and monocytes by RT-PCR. When transfected into 293 cells, porcine MDL-1 is expressed on the cell surface associated with DAP12.

Amino Acid Sequence↗
PubMed2001

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with neurobehavioral test scores in South Korean lead workers.

The authors performed a cross-sectional study to evaluate associations between blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead and measures of neurobehavioral and peripheral nervous system function among 803 lead-exposed workers and 135 unexposed controls in South Korea. The workers and controls were enrolled in the study between October 1997 and August 1999. Central nervous system function was assessed with a modified version of the World Health Organization Neurobehavioral Core Test Battery. Peripheral nervous system function was assessed by measuring pinch and grip strength and peripheral vibration thresholds. After adjustment for covariates, the signs of the beta coefficients for blood lead were negative for 16 of the 19 tests and blood lead was a significant predictor of worse performance on eight tests. On average, for the eight tests that were significantly associated with blood lead levels, an increase in blood lead of 5 microg/dl was equivalent to an increase of 1.05 years in age. In contrast, after adjustment for covariates, tibia lead level was not associated with neurobehavioral test scores. Associations with DMSA-chelatable lead were similar to those for blood lead. In these currently exposed workers, blood lead was a better predictor of neurobehavioral performance than was tibia or DMSA-chelatable lead, mainly in the domains of executive abilities, manual dexterity, and peripheral motor strength.

Adult↗