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Biomedical subjects

Y K Kim

Publications and source records attributed to Y K Kim.

At least 55 records · Page 3Linked to original sources

Activation of p21(WAF1/Cip1) transcription through Sp1 sites by histone deacetylase inhibitor apicidin: involvement of protein kinase C.

We previously reported that apicidin, a novel histone deacetylase inhibitor, inhibited the proliferation of tumor cells via induction of p21(WAF1/Cip1). In this study, we determined the molecular mechanisms by which apicidin induced the p21(WAF1/Cip1) gene expression in HeLa cells. Apicidin induced p21(WAF1/Cip1) mRNA independent of the de novo protein synthesis and activated the p21(WAF1/Cip1) promoter through Sp1-3 site located at -82 and -77 relative to the transcription start site. This transcriptional activation appears to be mediated by protein kinase C (PKC), because calphostin C, a PKC inhibitor, significantly attenuated the activation of p21(WAF1/Cip1) promoter via Sp1 sites, which was accompanied by a marked suppression of p21(WAF1/Cip1) mRNA and protein expression induced by apicidin. Consistent with the transcriptional activation of p21(WAF1/Cip1) promoter by apicidin, apicidin treatment led to the translocation of PKCepsilon from cytosolic to particulate fraction, which was reversed by pretreatment with calphostin C, indicating the involvement of PKC in the transcriptional activation of p21(WAF1/Cip1) via Sp1 sites by apicidin. However, the PKC-mediated transcriptional activation of p21(WAF1/Cip1) by apicidin appears to be independent of the histone hyperacetylation, because apicidin-induced histone hyperacetylation was not affected by calphostin C. Furthermore, a PKC activator, phorbol 12,13-dibutyrate, alone induced the transcriptional activation of p21(WAF1/Cip1) promoter, p21(WAF1/Cip1) mRNA, and protein expression without induction of the histone hyperacetylation, suggesting that the transcriptional activation of p21(WAF1/Cip1) by apicidin might have been mediated by a mechanism other than chromatin remodeling through the histone hyperacetylation. Taken together, these results suggest that the PKC signaling pathway plays a pivotal role in the transcriptional activation of the p21(WAF1/Cip1) gene by apicidin.

Biological Transport↗

Regulation of sensorimotor gating in rats by hippocampal NMDA: anatomical localization.

Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor gating that is reduced in humans with certain neuropsychiatric disorders, including schizophrenia, and in rats after manipulations of limbic cortico-striato-pallido-pontine circuitry. We have reported that PPI is reduced after specific manipulations of the hippocampal complex (HPC) in rats, but the mechanisms for these effects remain poorly understood. For example, dopaminergic substrates clearly regulate PPI, but the PPI-disruptive effects of intra-HPC carbachol or NMDA are not reversed by D2 receptor antagonists. This study examined the anatomical specificity within the hippocampal complex of the PPI-disruptive effects of NMDA infusion. Startle magnitude and PPI were assessed after acute bilateral infusion of NMDA (0, 0.4 or 0.8 microg) into the dorsal subiculum (DS), region CA1, the ventral subiculum (VS), the rostral entorhinal cortex (ECr) and the caudal entorhinal cortex (ECc). A dorsal-ventral gradient for NMDA effects was observed, with a dose-dependent disruption of PPI after NMDA infusion into the VS or EC, but not the DS, and with intermediate level effects observed after NMDA infusion into CA1. A second set of studies confirmed that the failure of NMDA effects in the DS did not reflect site-related differences in startle magnitude or baseline levels of PPI. These findings demonstrate the importance of the ventral, but not the dorsal HPC, in the glutamatergic regulation of PPI.

Animals↗

Suppression by a sesquiterpene lactone from Carpesium divaricatum of inducible nitric oxide synthase by inhibiting nuclear factor-kappaB activation.

Excessive nitric oxide (NO) produced by inducible NO synthase (iNOS) acts as a causative regulator in various inflammatory disease states. Carpesium divaricatum has been used in Korean traditional herbal medicine for its antipyretic, analgesic, vermifugic, and anti-inflammatory properties. We investigated the molecular mechanism for the suppression of lipopolysaccharide/interferon-gamma (LPS/IFN-gamma)-induced NO production in RAW 264.7 macrophages by the sesquiterpene lactone 2beta,5-epoxy-5,10-dihydroxy-6alpha-angeloyloxy-9beta-isobutyloxy-germacran-8alpha,12-olide (C-1), which has been identified recently as a new compound from C. divaricatum. C-1 decreased NO production in LPS/IFN-gamma-stimulated RAW 264.7 cells in a concentration-dependent manner, with an IC50 of approximately 2.16 microM; however, it had no direct effect on the iNOS activity of fully LPS/IFN-gamma-stimulated RAW 264.7 cells. Furthermore, treatment with C-1 led to a decrease in iNOS protein and mRNA. These effects appear to be due to inhibition of nuclear factor-kappaB (NF-kappaB) activation through a mechanism involving stabilization of the NF-kappaB/inhibitor of the kappaB (I-kappaB) complex, since inhibition of NF-kappaB DNA binding activity by C-1 was accompanied by a parallel reduction of nuclear translocation of subunit p65 of NF-kappaB and I-kappaBalpha degradation. Taken together, the results suggest that the ability of C-1 to inhibit iNOS gene expression may be responsible, in part, for its anti-inflammatory effects.

Animals↗

Development of liquid chromatographic method for the analysis of kanamycin residues in varicella vaccine using phenylisocyanate as a derivatization reagent.

A liquid chromatographic method for the determination of the aminoglycoside kanamycin in varicella vaccine is described. Kanamycin sulfate was derived with phenylisocyanate (PIC) and triethylamine for 10 min at 70 degrees C and chromatographed on a alkylamide-bonded column, Suplex pKb-100. A derivative of kanamycin sulfate was attached to four phenylisocynato groups and that molecular mass was confirmed with liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The kanamycin-PIC derivative was found to have a retention time of 11.7 min using an eluent composed of 40% acetonitrile in water at 1.2 ml/min column flow-rate. Detection was at a wavelength of 240 nm. Recoveries ranging from 97.5 to 99.8% were found. The correlation coefficient was greater than 0.9998 over the range between 10 and 100 microg/ml. The method precision of within-day assay showed a 0.5 to 4.0% coefficient of variation (n = 5) ranging from 10 to 70 microg/ml of kanamycin concentration levels. Kanamycin-PIC derivative in reaction solution was stable for 24 h at room temperature. A simple and efficient method for the analysis of the kanamycin in varicella vaccine was developed and validated.

Anti-Bacterial Agents↗

Purification and characterization of protein methylase II from Helicobacter pylori.

Protein methylase II (AdoMet:protein-carboxyl O-methyltransferase, EC 2.1.1.24) was identified and purified 115-fold from Helicobacter pylori through Q-Sepharose ion exchange column, AdoHcy-Sepharose 4B column, and Superdex 200 HR column chromatography using FPLC. The purified preparation showed two protein bands of about 78 kDa and 29 kDa molecular mass on SDS-PAGE. On non-denaturing gel electrophoresis, the enzyme migrated as a single band with a molecular mass of 410 kDa. In addition, MALDI-TOF-MS analysis and Superdex 200 HR column chromatography of the purified enzyme showed a major mass signal with molecular mass values of 425 kDa and 430 kDa, respectively. Therefore, the above results led us to suggest that protein methylase II purified from H. pylori is composed of four heterodimers with 425 kDa (4x(78+29)=428 kDa). This magnitude of molecular mass is unusual for protein methylases II so far reported. The enzyme has an optimal pH of 6.0, a K(m) value of 5.0x10(-6) M for S-adenosyl-L-methionine and a V(max) of 205 pmol methyl-(14)C transferred min(-1) mg(-1) protein.

Amino Acid Sequence↗

Differential regulation of protein tyrosine kinase on free radical production, granule enzyme release, and cytokine synthesis by activated murine peritoneal macrophages.

The present study examined the regulatory effect of tyrosine kinase inhibitors (genistein, tyrphostin, and 2,5-dihydroxycinnamate) on the free radical production, granule enzyme release, and synthesis of interleukin (IL)-8 and granulocyte macrophage-colony stimulating factor (GM-CSF) in murine peritoneal macrophages exposed to different stimulators [10 ng/mL of IL-1, 1 microgram/mL of lipopolysaccharide (LPS), and 1 microM N-formyl-methionyl-leucyl-phenylalanine (fMLP)]. Protein tyrosine kinase (PTK) inhibitors attenuated the stimulated superoxide, hydrogen peroxide, and nitric oxide production in macrophages stimulated with IL-1, LPS, or fMLP. N,N-Dimethylsphingosine (DMS) alone stimulated superoxide and hydrogen peroxide production by intact macrophages, but at 45 microM the stimulatory effect on superoxide production was not found. In contrast, DMS attenuated nitric oxide production by macrophages. High concentrations of DMS, tyrphostin, and 2,5-dihydroxycinnamate showed cytotoxic effects. PTK inhibitors did not exhibit a significant effect on granule enzyme release induced by IL-1, whereas they attenuated the effect of LPS and fMLP on degranulation. Genistein and tyrphostin decreased the production of IL-8 and GM-CSF in macrophages activated by IL-1, whereas 2,5-dihydroxycinnamate did not affect it. The results suggest that tyrosine kinases exposed to IL-1, LPS, and fMLP may exert different modulatory actions on macrophage responses. The IL-1-activated macrophage responses, particularly degranulation, appear to be differently regulated by tyrosine kinases compared with the responses activated by LPS and fMLP.

Animals↗

Evaluation of rapid immunocapture assays for diagnosis of Plasmodium vivax in Korea.

The rapid immunocapture assays, OptiMal and ICT, were evaluated from 87 individuals for the diagnosis of malaria infections directly from whole blood. A total of 87 individuals was examined for malaria parasites by microscopic examination of Giemsa-stained blood smears, and 65 cases were positive for Plasmodium vivax by microscopy. Correspondingly, the OptiMal test identified malaria infection in 45 cases (69.2%) of microscopy positive cases. Of these, two cases were misinterpreted as Plasmodium falciparum, whereas ICT detected P. vivax infection in 29 (44.6%) patients. We would like to propose that rapid immuno capture assays are an easy method that can serve as a useful tool in addition to microscopy for the diagnosis of malaria, but sensitivity is not yet satisfactory for diagnosis of P. vivax in Korea.

Animals↗

Age-hardening reactions in a type III dental gold alloy.

The age-hardening reactions in a commercial type III dental gold alloy were studied by means of hardness test, X-ray diffraction study and scanning and transmission electron microscopic observations. The hardening was attributed to the formation of the metastable AuCu 1' type ordered phase in the grain interior by the isothermal ageing at 225 and 450 degrees C at which two hardness peaks were observed by the isochronal ageing. By ageing at 450 degrees C, the hardening did not begin immediately because the incubation period was required. The age hardening at 225 degrees C was characterized by a slow growth rate of the metastable AuCu 1' type ordered phase. The overageing with softening which occurred following prolonged ageing at 450 degrees C was due to the formation of the lamellar structure composed of the Ag-rich alpha1 and AuCu 1 type ordered phases at grain boundaries.

Dental Alloys↗

Optical organophosphorus biosensor consisting of acetylcholinesterase/viologen hetero Langmuir-Blodgett film.

The fiber-optic biosensor consisting of an acetylcholinesterase (AChE)-immobilized Langmuir-Blodgett (LB) film was developed to detect organophosphorus compounds in contaminated water. The sensing scheme was based on the decrease of yellow product, o-nitrophenol, from a colorless substrate, o-nitrophenyl acetate, due to the inhibition by organophosphorus compounds on AChE. Absorbance change of the product as the output of enzyme reaction was detected and the light was guided through the optical fibers. The enzyme portion of the sensor system was fabricated by the LB technique for formation of the enzyme film. AChE-immobilized LB film was formed by adsorbing the enzyme molecules onto a viologen monolayer using the electrostatic force. The proposed kinetics for irreversible inhibition of organophosphorus compounds on AChE agreed well with the experimental data. The surface topography of AChE-immobilized LB film was investigated by atomic force microscope (AFM). The immobilized AChE had the maximum activity at pH 7. The proposed biosensor could successfully detect the organophosphorus compounds up to 2 ppm and the response time to steady signal of the sensor was about 10 min.

Acetylcholinesterase↗

Distribution and cytokine production of CD4 and CD8 T-lymphocyte subsets in patients with acute asthma attacks.

BACKGROUND: The activation of T cells and the elevation of Th2-type cytokines have been observed in asthmatic patients, but the relative role of CD4 and CD8 T cell is still unclear. OBJECTIVE: To investigate the role of T cell subset in patients with acute asthma attacks, we analyzed the distribution, activation status, and cytokine production of CD4 and CD8 cells. METHODS: The percentages of the CD4 and CD8 cell in peripheral blood (PB) and bronchoalveolar lavage (BAL) fluid were analyzed by flow cytometry. The cytokines (IL-4, IL-5, and IFN-gamma) and soluble IL-2 receptor (sIL-2R) were measured by ELISA in culture supernatants of CD4 and CD8 cells purified from PB. RESULTS: The CD4/CD8 ratio in PB of asthmatic patients was significantly higher than that of controls, which was significantly reduced after treatment. In contrast, there was a tendency to high percentage of CD8 cells in asthmatic patients as compared with controls in BAL, which resulted in a decreased CD4/CD8 ratio. Comparing the T cell subsets in BAL with paired PB in asthma, the CD4 cells were higher in PB, but CD8 cells were higher in BAL. The IL-4, IL-5, and sIL-2R produced by CD4 cells were significantly higher than those produced by CD8 cells in asthmatic patients. CONCLUSIONS: Our results provide evidence that activated CD4 T cells increase and produce type 2 cytokines in PB, but CD8 T cell are more sequestrated than CD4 T cells in the airway during an acute asthma attack.

Acute Disease↗

Differences in sensitization rates to outdoor aeroallergens, especially citrus red mite (Panonychus citri), between urban and rural children.

BACKGROUND: A recent investigation has suggested that citrus red mite (Panonychus citri, CRM) is the most important allergen in citrus-cultivating farmers with asthma and allergic rhinitis. OBJECTIVE: A cross-sectional survey was performed to evaluate the prevalence of asthma and chronic rhinitis symptoms and sensitization to common indoor and outdoor aeroallergens, including CRM and Japanese cedar pollen, in rural and urban Korean children. METHODS: A total of 2,055 children (1,055 subjects living in rural areas with citrus farms and 1,000 controls in urban areas without citrus farms) were enrolled. They were evaluated by a questionnaire, and by skin prick tests with 13 common indoor and outdoor aeroallergens, including CRM and Japanese cedar pollen. RESULTS: The prevalence of wheezing and chronic rhinitis symptoms during the last 12 months was 8.3% and 35.7% in the rural children and 10.5% and 22.4% in the control group. The most common sensitizing allergens in order of decreasing frequency were Dermatophagoides pteronyssinus (26.6%), Dermatoplagoides farinae (22.7%), CRM (14.2%), cockroach (11.3%), and Japanese cedar pollen (9.7%) among the rural children, but the sensitization rates to CRM and Japanese cedar pollen were 1.3% and 0.2% among the control children, respectively. The prevalence of wheeze during the last 12 months was not different between rural children with sensitization to CRM or Japanese cedar pollen and those without sensitization (5.4% vs 6.1%; 6.9% vs 5.9%). However, the prevalence of chronic rhinitis during the last 12 months was higher among those with sensitization to CRM or to Japanese cedar pollen than among those without sensitization (40.8% vs 34.4%; 51.5% vs 33.5%). CONCLUSIONS: CRM is a common sensitizing allergen in rural children, and the sensitization rates to outdoor aeroallergens, especially CRM and Japanese cedar pollen, are very different between children from rural and urban areas in Korea.

Adolescent↗

Repeated exposure to low levels of sulfur dioxide (SO2) enhances the development of ovalbumin-induced asthmatic reactions in guinea pigs.

BACKGROUND: Sulfur dioxide (SO2) is one of the major air pollutants. It is known to aggravate asthma symptoms in human beings, but few studies have focused on the effects of SO2 upon the development of bronchial asthma in animal models. OBJECTIVE: This study was undertaken to evaluate the role of SO2 upon the development of ovalbumin (OA)-induced asthmatic reactions in guinea pigs. METHODS: Guinea pigs were divided into four groups: (1) OA- and SO2-exposed group (n = 12), (2) SO2-exposed group (n = 12), (3) OA-exposed group (n = 11), and (4) saline-exposed group (n = 7). Guinea pigs of the first and second groups were exposed to 0.1 ppm SO2 for 5 hours a day on 5 consecutive days. Guinea pigs in the first and third groups inhaled 0.1% OA aerosols for 45 minutes a day on days 3, 4, and 5. One week after the sensitization procedure, all the guinea pigs underwent bronchial challenge with 1.0% OA aerosols, using unrestricted whole-body plethysmography. Bronchoalveolar lavage and histopathologic examination were performed 24 hours after the bronchial challenge. RESULTS: Increases in enhanced pause (Penh), as an index of airway obstruction, after the bronchial challenge was significantly higher in OA- and SO2-exposed group (group 1) than the other groups (P < .05, respectively). Eosinophil counts in bronchoalveolar lavage fluids were also significantly higher in group 1 than in the other groups (P < .05, respectively). Histopathologic findings of bronchial and lung tissue in the group 1 showed an infiltration of inflammatory cells, bronchiolar epithelial damage, and mucus and cell plug in the lumen, but no significant abnormalities were observed in the other groups. CONCLUSIONS: These results indicate that repeated exposure to low levels of sulfur dioxide may enhance the development of ovalbumin-induced asthmatic reactions in guinea pigs.

Air Pollutants↗

Outdoor air pollutants derived from industrial processes may be causally related to the development of asthma in children.

BACKGROUND: There is no consistent evidence that outdoor air pollutants are involved in the development of asthma. OBJECTIVE: The aim of this study was to determine whether outdoor air pollutants derived from industrial processes were related to the prevalence of asthma, bronchial hyperresponsiveness, and atopy in exposed children. METHODS: A total of 7,511 children from 7 to 12 years of age were recruited in the study. Eight hundred eighty-eight of 1,009 (88%) of the subjects living around industrial factories and 5,998 of 6,502 (92%) living in a less polluted neighboring area responded to the ISAAC questionnaire. A total of 1,492 subjects 8 to 9 years old underwent skin prick tests for 11 common aeroallergens. A total of 732 of the subjects from 8 to 9 years of age underwent bronchial provocation tests with hypertonic saline (BPT-HS). RESULTS: The prevalence of ever experiencing wheezing and wheeze during the last 12 months was 25.6%, and 18.8% among the children living in the more polluted area. This was significantly higher than for those living in the less polluted area (14.2% and 9.0%, respectively). The positive rate of BPT-HS (the provocative dose of hypertonic saline causing 20% fall of FEV, < or = 23 mL) was higher among those in the more polluted area than in children living in the less polluted area (12.2% vs 7.5%). However, the rate of atopy based on the skin tests was the same in the two groups (28.3% vs 30.6%). CONCLUSIONS: The prevalence of asthma and bronchial hyperresponsiveness was higher among children living around the heavily industrial area compared with those living in the less polluted area, despite similar atopic sensitization.

Air Pollutants↗

H2O2-induced cell death in human glioma cells: role of lipid peroxidation and PARP activation.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of a number of neurodegenerative disorders. However, the underlying mechanism of ROS-induced cell injury remains to be defined. This study was undertaken to examine the role of lipid peroxidation and poly (ADP-ribose) polymerase (PARP) activation in H2O2-induced cell death in A172 cells, a human glioma cell line. H2O2 induced a dose- and time-dependent cell death. The cell death was prevented by thiols (dithiothreitol and glutathione), iron chelators (deferoxamine and phenanthroline), H2O2 scavengers (catalase and pyruvate), and a hydroxyl radical scavenger (dimethylthiourea). Antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD) and Trolox had no effect on the H2O2-induced cell death. Lipid peroxidation did not increase in human glioma cells exposed to H2O2. The PARP inhibitor 3-aminobenzamide prevented the cell death induced by H2O2. The PARP activity was increased by H2O2 and the H2O2 effect was prevented by 3-aminobenzamide, dithiothreitol, and phenanthroline. The ATP depletion induced by H2O2 was prevented by catalase, dithiothreitol, phenanthroline, and 3-aminobenzamide, but not by DPPD. These results indicate that the H2O2-induced cell death is mediated by PARP activation but not by lipid peroxidation in human glioma cells.

Benzamides↗

Role of reactive oxygen species and glutathione in inorganic mercury-induced injury in human glioma cells.

The present study was undertaken to examine the role of reactive oxygen species (ROS) and glutathione (GSH) in glia cells using human glioma cell line A172 cells. HgCl2 caused the loss of cell viability in a dose-dependent manner. HgCl2-induced loss of cell viability was not affected by H2O2 scavengers catalase and pyruvate, a superoxide scavenger superoxide dismutase, a peroxynitrite scavenger uric acid, and an inhibitor of nitric oxide N(G)-nitro-arginine Methyl ester. HgCl2 did not cause changes in DCF fluorescence, an H2O2-sensitive fluorescent dye. The loss of cell viability was significantly prevented by the hydroxyl radical scavengers dimethylthiourea and thiourea, but it was not affected by antioxidants DPPD and Trlox. HgCl2-induced loss of cell viability was accompanied by a significant reduction in GSH content. The GSH depletion was almost completely prevented by thiols dithiothreitol and GSH, whereas the loss of viability was partially prevented by these agents. Incubation of cells with 0.2 mM buthionine sulfoximine for 24 hr, a selective inhibitor of gamma-glutamylcysteine synthetase, resulted in 56% reduction in GSH content without any change in cell viability. HgCl2 resulted in 34% reduction in GSH content, which was accompanied by 59% loss of cell viability. These results suggest that HgCl2-induced cell death is not associated with generation of H2O2 and ROS-induced lipid peroxidation. In addition, these data suggest that the depletion of endogenous GSH itself may not play a critical role in the HgCl2-induced cytotoxicity in human glioma cells.

Brain Neoplasms↗

Dual diagnosis: HIV and mental illness, a population-based study.

This is a cross-sectional, population-based (n = 378,710) study using hospital discharge abstract data to determine the relative risk associated with having a dual diagnosis of mental illness and HIV/AIDS. The analysis addresses issues of gender, race, and age, as well as types of mental illness. Persons with a mental illness are 1.44 times more likely to have HIV/AIDS. Women are at increased risk of being dually diagnosed. There are no risk differences by race. Those with a specific diagnosis of substance abuse or a depressive disorder are more likely to have a diagnosis of HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

Citrus red mite (Panonychus citri) may be an important allergen in the development of asthma among exposed children.

BACKGROUND: Recent investigations have demonstrated that spider mites are important allergens in the development of asthma in fruit-cultivating farmers. OBJECTIVE: The aim of this study was to evaluate the sensitization rate to the citrus red mite (Panonychus citri) in children living in rural areas, and to determine the allergenic cross-reactivity with other mites. METHODS: A total of 7254 children (ages 7-15 years) living in rural areas were enrolled, and each subject was evaluated by a questionnaire and a skin prick test. Allergenic cross-reactivity was evaluated by ELISA inhibition tests. RESULTS: The most common sensitizing allergens were house dust mites, followed by citrus red mite and cockroach. High serum-specific IgE bindings to the citrus red mite were detected in 21 of 100 randomly selected subjects. The prevalence of asthma was higher among those with positive skin responses to the citrus red mite than with negative skin responses to this mite. ELISA inhibition tests showed that IgE bindings to this mite were minimally inhibited with additions of domestic mites. CONCLUSION: Spider mites such as the citrus red mite may be important outdoor allergens among children living in rural areas, and spider mite-derived allergens have unique allergenic determinants compared with domestic mites.

Adolescent↗