Biomedical subjects

S K Han

Publications and source records attributed to S K Han.

At least 37 records · Page 2Linked to original sources

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

Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides.

Apolipoprotein E plays an important role in recovery from acute brain injury and risk of developing Alzheimer's disease. We demonstrate that biologically relevant concentrations of apoE suppress microglial activation and release of TNFalpha and NO in a dose-dependent fashion. Peptides derived from the apoE receptor-binding region mimic the effects of the intact protein, whereas deletion of apoE residues 146-149 abolishes peptide bioactivity. These results are consistent with the hypothesis that apoE modulates microglial function by binding specific cell surface receptors and that the immunomodulatory effects of apoE in the central nervous system may account for its role in acute and chronic neurological disease.

Animals↗

PubMed2001

Performance of UASB reactor treating leachate from acidogenic fermenter in the two-phase anaerobic digestion of food waste.

This study was conducted to investigate the performance of the upflow anaerobic sludge blanket (UASB) reactor treating leachate from acidogenic fermenter in the two-phase anaerobic digestion of food waste. The chemical oxygen demand (COD) removal efficiency was consistently over 96% up to the loading rates of 15.8 g COD/l d. The methane production rate increased to 5.51/l d. Of all the COD removed, 92% was converted to methane and the remaining presumably to biomass. At loading rates over 18.7 g COD/l d, the COD removal efficiency decreased due to sludge flotation and washout in the reactor, which resulted from short HRT of less than 10.6 h. The residual propionate concentration was the highest among the volatile fatty acids (VFA) in the effluent. The specific methanogenic activity (SMA) analysis showed that the VFA-degrading activity of granule was the highest for butyrate, and the lowest for propionate. Typical granules were found to be mainly composed of microcolonies of Methanosaeta. The size distribution of sludge particles indicated that partially granulated sludge could maintain the original structure of granular sludge and continue to gain size in the UASB reactor treating leachate from acidogenic fermenter.

Acids↗

PubMed2001

Activation of metabotropic glutamate receptors inhibits GABAergic transmission in the rat subfornical organ.

Glutamate is known to increase neuronal excitability in the subfornical organ, a circumventricular organ devoid of the blood-brain barrier. To understand the synaptic mechanism of neuronal excitation by glutamate in this nucleus, we examined the effects of glutamate on GABAergic spontaneous inhibitory postsynaptic currents recorded from subfornical organ neurons in the rat brain slice. The baseline frequency, amplitude and decay time-constant of such spontaneous synaptic currents were 5.60 Hz, 119 pA and 17.3 ms, respectively. Glutamate (10-1000 microM) selectively inhibited the frequency of spontaneous GABAergic inhibitory postsynaptic currents (half-maximal effective concentration=47 microM) with little effects on their amplitudes and decay time constants. The inhibitory effect of glutamate on the frequency of spontaneous GABAergic postsynaptic currents was not blocked by tetrodotoxin (1 microM), or by the antagonists of ionotropic glutamate receptors. In contrast, such inhibitory effect of glutamate was mimicked by general or group II selective metabotropic glutamate receptor agonists such as DCGIV (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (half-maximal effective concentration=112 nM), but not by the agonists for group I or group III metabotropic glutamate receptors. Under current clamp mode, glutamate reduced the frequencies of spontaneous inhibitory postsynaptic potentials and action potentials in subfornical organ neurons. Our data indicate that glutamate decreases the frequency of spontaneous inhibitory postsynaptic currents by acting on the group II metabotropic glutamate receptors on axonal terminals in the subfornical organ. From these results we suggest that the glutamate-induced modulation of tonic GABAergic inhibitory synaptic activity can influence the excitability of subfornical organ neurons.

Animals↗

PubMed2001

Multi-step sequential batch two-phase anaerobic composting of food waste.

This study was conducted to evaluate the newly devised process, called MUlti-step Sequential batch Two-phase Anaerobic Composting (MUSTAC). The MUSTAC process consisted of several leaching beds for hydrolysis, acidification and post-treatment, and a UASB reactor for methane recovery. This process to treat food waste was developed with a high-rate anaerobic composting technique based on the rate-limiting step approach. Rumen microorganisms were inoculated to improve the low efficiency of acidogenic fermentation. Both two-phase anaerobic digestion and sequential batch operation were used to control environmental constraints in anaerobic degradation. The MUSTAC process demonstrated excellent performance as it resulted in a large reduction in volatile solids (VS) (84.7%) and high methane conversion efficiency (84.4%) at high organic loading rates (10.8 kg VS m(-3) d(-1)) in a short SRT (10 days). Methane yield was 0.27 m3 kg(-1) VS, while methane gas production rate was 2.27 m3 m(-3) d(-1). The output from the post-treatment could be used as a soil amendment, which was produced at the same acidogenic fermenter without troublesome moving. The main advantages of the MUSTAC process were simple operation and high efficiency. The MUSTAC process proved stable, reliable and effective in resource recovery as well as waste stabilization.

Animals↗

PubMed2001

Joint QSAR analysis using the Free-Wilson approach and quantum chemical parameters.

A new quantitative structure-activity relationship (QSAR) technique combining the Free-Wilson method and constructed quantum chemical parameters was used to simulate the aqueous solubility (Sw), 1-octanol/water partition coefficient (Kow) of 14 new synthesized benzanilide derivatives and their 96 h acute toxicity (EC50) to Daphnia magna. The mode of action of the 14 selected compounds to Daphnia magna was shown to be a complex process involving a physical partition stage and a bio-chemical reaction stage. The results also indicated that the joint (QSAR) analysis was much effective than the original Free-Wilson method and Hansch method not only in predicting properties/toxicity, but also in investigating the mode of action of chemicals.

1-Octanol↗

PubMed2001

Effect of acetylsalicylic acid on endogenous I kappa B kinase activity in lung epithelial cells.

The anti-inflammatory effect of acetylsalicylic acid (ASA) has been thought to be secondary to the inhibition of prostaglandin synthesis. Because doses of ASA necessary to treat chronic inflammatory diseases are much higher than those needed to inhibit prostaglandin synthesis, a prostaglandin-independent pathway has been emerging as the new anti-inflammatory mechanism of ASA. Here, we examined the effect of ASA on the interleukin (IL)-1 beta- and tumor necrosis factor (TNF)-alpha-induced proinflammatory cytokine expression and evaluated whether this effect is closely linked to the nuclear factor (NF)-kappa B/I kappa B-alpha pathway. A high dose of ASA blocked IL-1 beta- and TNF-alpha-induced TNF-alpha and IL-8 expression, respectively. ASA inhibited TNF-alpha-induced activation of NF-kappa B by preventing phosphorylation and subsequent degradation of I kappa B-alpha in a prostanoid-independent manner. TNF-alpha-induced activation of I kappa B kinase was also suppressed by ASA pretreatment. These observations suggest that the anti-inflammatory effect of ASA in lung epithelial cells may be due to suppression of I kappa B kinase activity, which thereby inhibits subsequent phosphorylation and degradation of I kappa B-alpha, activation of NF-kappa B, and proinflammatory cytokine expression in lung epithelial cells.

Aspirin↗

PubMed2001

Anti-inflammatory effect of adenovirus-mediated IkappaBalpha overexpression in respiratory epithelial cells.

Many studies into basic biological characteristics of inflammation and tissue injury have implicated pro-inflammatory cytokine-mediated tissue injury in the pathogenesis of inflammatory lung diseases. Because transcription of most proinflammatory cytokines is dependent on the activation of nuclear factor (NF)-kappaB, NF-kappaB could be a good potential target to suppress the cytokine cascade. Cytokine-induced activation of NF-kappaB requires phosphorylation and subsequent degradation of IkappaBa. Therefore, the blocking NF-kappaB activation by IkappaBalpha could inhibit the pro-inflammatory cytokine-induced tissue injury. To evaluate whether blocking of NF-kappaB activation shows an anti-inflammatory effect, this study investigated the effect of adenovirus-mediated overexpression of IkappaBalpha super-repressor (IkappaBalpha-SR) on the pro-inflammatory cytokine expression in respiratory epithelial cells. The transduction efficiency of adenovirus was >90% in both A549 and NCI-H157 cells. Ad5IkappaBalpha-SR-transduced cells expressed high levels of IkappaBalpha-SR, which was resistant to tumour necrosis factor (TNF)-alpha-induced degradation. Adenovirus-mediated overexpression of IkappaBalpha-SR blocked cytokine-induced nuclear translocation of p65 and NF-kappaB deoxyribonucleic acid binding activity without affecting total cellular expression level of NF-kappaB. Ad5IkappaBalpha-SR transduction suppressed cytokine-induced interleukin-8 and TNF-alpha expressions at both ribonucleic acid and protein levels. These results suggest that blocking the nuclear factor-kappaB pathway by adenovirus-mediated overexpression of IkappaBalpha-super-repressor shows an effective anti-inflammatory effect in respiratory epithelial cells.

Adenoviridae↗

PubMed2001

Surgical treatment of digital ischemia occurred after radial artery catheterization.

Permanent ischemic injury of the hand after radial artery cannulation is rare, but several cases of thromboembolism after the cannulation leading to amputation of affected limb or digits have been reported. A 48-yr-old man undergoing spine surgery showed normal modified Allen's test and had no preoperative vascular disease. We inserted 20-G radial artery catheter for the continuous monitoring of the blood flow and serial blood sampling. There was no specific event during the operation and the catheter was removed immediately after the operation. The signs and symptoms of the circulatory impairment of the radial artery developed four days after the operation and aggravated thereafter. Through the angiographic study, we found the total occlusion of the radial artery and some of its branches. After an emergent surgical exploration of the radial artery for removal of the thrombus and vein graft for the defect of the artery on the 8th postoperative day, the ischemic signs and symptoms disappeared and the radial pulse was restored.

Catheterization, Peripheral↗

PubMed2001

Hepatopulmonary syndrome in poorly compensated postnecrotic liver cirrhosis by hepatitis B virus in Korea.

BACKGROUND: Hepatopulmonary syndrome (HPS) refers to the association of hypoxemia, intrapulmonary shunting and chronic liver disease. But there is no clear data about the prevalence of HPS in postnecrotic liver cirrhosis by hepatitis B virus (HBV), the most common cause of liver disease in Korea. The aim of this study was to investigate the prevalence of HPS in poorly compensated postnecrotic liver cirrhosis by HBV, and the correlation of the hepatopulmonary syndrome with clinical aspects of postnecrotic liver cirrhosis by HBV. METHODS: Thirty-five patients underwent pulmonary function test, arterial blood gas analysis and contrast-enhanced echocardiography. All patients were diagnosed as HBV-induced Child class C liver cirrhosis and had no evidence of intrinsic cardiopulmonary disease. RESULTS: Intrapulmonary shunt was detected in 6/35 (17.1%) by contrast-enhanced echocardiography. Two of six patients with intrahepatic shunts had significant hypoxemia (PaO2 < 70 mmHg) and four showed increased alveolar-arterial oxygen gradient over 20 mmHg. Only cyanosis could reliably distinguish between shunt positive and negative patients. CONCLUSIONS: The prevalence of intrapulmonary shunt in poorly compensated postnecrotic liver cirrhosis by HBV was 17.1% and the frequency of hepatopulmonary syndrome was relatively low (5.7%). 'Subclinical' hepatopulmonary syndrome (echocardiographically positive intrapulmonary shunt but without profound hypoxemia) exists in 11.4% of cases with poorly compensated postnecrotic liver cirrhosis by HBV. Cyanosis is the only reliable clinical indicator of HPS of HBV-induced poorly compensated liver cirrhosis. Further studies are required to determine if the prevalence and clinical manifestations of HPS varies with etiology or with geographical and racial differences.

Adult↗

PubMed2001

Differential effects of adenovirus-p16 on bladder cancer cell lines can be overcome by the addition of butyrate.

High frequency of p16 alteration and high local recurrence rate of bladder cancer make this cancer an ideal target for p16 gene therapy. However, a low transduction rate of p16 via adenoviral vector causes an inconsistent result. In this study, we have tested adenovirus-p16 in several bladder cancer cell lines and investigated a way of improving the low transduction rate. Adenovirus-p16 showed a strong antitumor effect on bladder cancer cell lines (253J and T24) with strong Coxackie-adenoviral receptor (CAR) expression but little antitumor effect on bladder cancer cell lines (J82 and HT1376) with little CAR expression. In this study, we suggest a simple way of overcoming the differential effects of the adenovirus. The addition of butyrate to media was found to increase the transduction rate of adenovirus remarkably and increase the antitumor effect of adenovirus-p16 in bladder cancer cell lines with little CAR expression. Butyrate effects were related with increased CAR expression on the cell surface as well as increased transgene expression from adenoviral vector. From these observations, application of adenovirus-p16 gene therapy with butyrate can overcome the obstacle of low gene transfer and enhance the antitumor effect of adenovirus-p16 in bladder cancer.

Adenoviridae↗

PubMed2001

Effect of nitrite and propolis preservative on volatile basic nitrogen changes in meat products.

Pig meat was treated with 0.3% ethanol extracted propolis (EEP), 0.3% water extracted propolis (WEP), 0.4% dried residue of ethanol extracted propolis (DREEP) and 0.2% potassium sorbate (PS). The samples were stored for 8 weeks at 4, 10 and 20 degrees C, respectively. Volatile basic nitrogen (VBN) tests were carried out to measure the influence of temperature after 0, 2, 4 and 8 weeks. The VBN value in 0.3% EEP pork sausages was the lowest for all treatments after 8 weeks of storage at 4 degrees C. The 0.3% EEP treatment was superior to the 0.2% PS treatment. This was due to the lower VBN of the former than that of the latter. Hence, EEP, WEP and DREEP can serve as good chemical preservatives of pork meat products and can contribute to promote human health because they are naturally produced.

Amino Acids↗

PubMed2001

Predicting octanol/water partition coefficient using solvation free energy and solvent-accessible surface area.

The regression model for octanol/water partition coefficients (Kow), is founded with only two molecular descriptors available through quantum chemical calculations: solvation free energy (delta Gs), and solvent-accessible surface area (SASA). For the properties of 47 organic compounds from 17 types, the model gives a correction coefficient (adjusted for degrees of freedom) of 0.959 and a standard error of 0.277 log unit. It is a suitable way to predict the partition properties that are related to solute-solvent interactions in the water phase.

Kinetics↗

PubMed2000

Mechanism of human group V phospholipase A2 (PLA2)-induced leukotriene biosynthesis in human neutrophils. A potential role of heparan sulfate binding in PLA2 internalization and degradation.

Human group V phospholipase A(2) (hVPLA(2)) has been shown to have high activity to elicit leukotriene production in human neutrophils (Han, S. K., Kim, K. P., Koduri, R., Bittova, L., Munoz, N. M., Leff, A. R., Wilton, D. C., Gelb, M. H., and Cho, W. (1999) J. Biol. Chem. 274, 11881-11888). To determine the mechanism by which hVPLA(2) interacts with cell membranes to induce leukotriene formation, we mutated surface cationic residues and a catalytic residue of hVPLA(2) and measured the interactions of mutants with model membranes, immobilized heparin, and human neutrophils. These studies showed that cationic residues, Lys(7), Lys(11), and Arg(34), constitute a part of the interfacial binding surface of hVPLA(2), which accounts for its moderate preference for anionic membranes. Additionally, hVPLA(2) binds heparin with high affinity and has a well defined heparin-binding site. The site is composed of Arg(100), Lys(101), Lys(107), Arg(108), and Arg(111), and is spatially distinct from its interfacial binding surface. Importantly, the activities of the mutants to hydrolyze cell membrane phospholipids and induce leukotriene biosynthesis, when enzymes were added exogenously to neutrophils, correlated with their activities on phosphatidylcholine membranes but not with their affinities for anionic membranes and heparin. These results indicate that hVPLA(2) acts directly on the outer plasma membranes of neutrophils to release fatty acids and lysophospholipids. Further studies suggest that products of hVPLA(2) hydrolysis trigger the cellular leukotriene production by activating cellular enzymes involved in leukotriene formation. Finally, the temporal and spatial resolution of exogenously added hVPLA(2) and mutants suggests that binding to cell surface heparan sulfate proteoglycans is important for the internalization and clearance of cell surface-bound hVPLA(2).

Biological Transport↗

PubMed2000

NF-kappaB activation is related to the resistance of lung cancer cells to TNF-alpha-induced apoptosis.

In diverse cell types, NF-kappaB transcription factors have been shown to have a role in regulating the apoptotic program, either as essential for the induction of apoptosis or, perhaps more commonly, as blockers of apoptosis. We investigated the role of NF-kappaB activation in the TNF-alpha-mediated apoptosis in lung cancer cells. TNF-alpha-resistant NCI-H157 cells became sensitized to TNF-alpha by prior treatment with cycloheximide, suggesting the presence of newly synthesized antiapoptotic protein(s). We next evaluated whether the transcription of antiapoptotic protein(s) depends on the activation of NF-kappaB. NF-kappaB activation was blocked by either adenovirus-mediated overexpression of IkappaBalpha superrepressor or pretreatment with proteasome inhibitor, MG132. Both methods of blocking NF-kappaB activation enhanced TNF-alpha-induced apoptosis in NCI-H157 cells. These results suggest that NF-kappaB activation confers resistance to TNF-alpha-mediated apoptosis in lung cancer cells.

Adenoviridae↗

PubMed2000

The molecular basis of phosphatidylcholine preference of human group-V phospholipase A2.

Human group-V phospholipase A(2) (hVPLA(2)) is a secretory phospholipase A(2) (PLA(2)) that is involved in eicosanoid formation in such inflammatory cells as macrophages and mast cells. We showed that hVPLA(2) can bind phosphatidylcholine membranes and hydrolyse phosphatidylcholine molecules much more efficiently than human group-IIa PLA(2), which accounts for its high activity on the outer plasma membrane of mammalian cells. To understand the molecular basis of the high phosphatidylcholine specificity of hVPLA(2), we mutated several residues (Gly-53, Glu-56 and Glu-57) that might be involved in interaction with an active-site-bound phospholipid molecule. Phospholipid head-group specificities of mutants determined using polymerized mixed-liposome substrates indicate that a small glycine residue in position 53 is important for accommodating a bulky choline head group. Also, results indicated that two anionic residues, Glu-56 and Glu-57, favourably interact with cationic head groups of phosphatidylcholine and phosphatidylethanolamine. Together, these steric and electrostatic properties of the active site of hVPLA(2) allow for effective binding and hydrolysis of a bulky cationic choline head group of phosphatidylcholine, which is unique among mammalian secretory PLA(2)s.

Amino Acid Sequence↗

PubMed2000

Anti-inflammatory effect of heat shock protein induction is related to stabilization of I kappa B alpha through preventing I kappa B kinase activation in respiratory epithelial cells.

Heat shock protein (HSP) induction confers protection against diverse forms of cellular and tissue injury. However, the mechanism by which HSP exerts cytoprotective effects is unclear. Because HSP induction inhibits genetic expression of pro-inflammatory cytokines, the transcription of which is dependent on NF-kappa B activation, we explored the relationship between the anti-inflammatory effect of HSP induction and the NF-kappa B/I kappa B alpha pathway. Both HS and sodium arsenite treatment increased HSP70 expression time dependently at mRNA and protein levels. Prior induction of HSP suppressed cytokine-induced IL-8 and TNF-alpha expression at both mRNA and protein levels. Although HSP induction did not affect total cellular expression of NF-kappa B, TNF-alpha-induced increase in NF-kappa B-DNA binding activity and nuclear translocation of the p65 subunit of NF-kappa B were inhibited by prior HSP induction, suggesting that activation of NF-kappa B was blocked. Cytokine-induced I kappa B alpha phosphorylation and its degradation were blocked in HSP-induced cells. Immune complex kinase assays demonstrated that TNF-alpha induced increase in I kappa B kinase activity was suppressed by prior HSP induction. These results suggest that the anti-inflammatory effect of HSP induction in respiratory epithelial cells is related to stabilization of I kappa B alpha, possibly through the prevention of I kappa B kinase activation, which thereby inhibits activation of NF-kappa B.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Biochemical, molecular and physiological characterization of a new beta-casein variant detected in Korean cattle.

There are seven known genetic variants of bovine beta-casein (beta-CN)--A1, A2, A3, B, C, D and E. In this study, we identified a new genetic variant (named beta-CN H) which migrates slower than the other variants in acidic starch gel electrophoresis. We confirmed through protein and DNA sequence analyses that the H variant differs at five residues from the A2 sequence: Arg25/Cys, Leu88/Ile, Gln117/Glu, Glu175/Gln and Gln195/Glu. Of these substitutions the 25th residue was contained in the casein phosphopeptide (CPP) region. In rats, calcium solubilizing effect of the CPP of bovine variant H was increased by approximately 23% compared with that of the CPP of non-H. Using extensive Korean Bos taurus pedigrees, we confirmed that beta-CN H was controlled by a codominant allele.

Animals↗