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Biomedical subjects

Y C Park

Publications and source records attributed to Y C Park.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nitric oxide synthesis and TNF-alpha secretion in RAW 264.7 macrophages: mode of action of a fermented papaya preparation.

Macrophage inducible nitric oxide synthase is able to generate massive amounts of nitric oxide (NO) which contributes to the host immune defense against viruses and bacteria. Monocyte-macrophages stimulated with the bacterial wall component lipopolysaccharide (LPS) and cytokines such as interferon-gamma (IFN-gamma) express the inducible form of nitric oxide synthase (iNOS). Furthermore, tumor necrosis factor-alpha (TNF-alpha) is one of the central regulatory cytokines in macrophage antimicrobial activity and synergizes with IFN-gamma in the induction of NO synthesis. Because of its pivotal role in both antimicrobial and tumoricidal activities of macrophages, a significant effort has focused on developing therapeutic agents that regulate NO production. In the present study fermented papaya preparation (FPP) is shown to exert both immunomodulatory and antioxidant activity in the macrophage cell line RAW 264.7. Interestingly, a low and a high molecular weight fraction (LMF and HMF, respectively) of FPP exhibited different activity patterns. FPP fractions alone did not affect NO production. However in the presence of IFN-gamma, both LMF and HMF significantly increased iNOS activity and nitrite as well as nitrate accumulation. NO radical formation measured in real-time by electron paramagnetic resonance spectroscopy was higher in the presence of LMF and IFN-gamma. On the contrary, iNOS mRNA levels were enhanced further with HMF than with LMF. Moreover, LMF displayed a stronger superoxide anion scavenging activity than HMF. In the presence of IFN-gamma, both FPP fractions stimulated TNF-alpha secretion. However in non-stimulated macrophages, TNF-alpha secretion was enhanced by HMF only. Since water-soluble FPP fractions contained no lipid A, present data indicate that FPP is a macrophage activator which augments nitric oxide synthesis and TNF-alpha secretion independently of lipopolysaccharides.

Animals↗
PubMed2000

A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction.

TRAF proteins are major mediators for the cell activation, cell survival, and antiapoptotic functions of the TNF receptor superfamily. They can be recruited to activated TNF receptors either by direct interactions with the receptors or indirectly via the adaptor protein TRADD. We now report the structure of the TRADD-TRAF2 complex, which is highly distinct from receptor-TRAF2 interactions. This interaction is significantly stronger and we show by an in vivo signaling assay that TRAF2 signaling is more readily initiated by TRADD than by direct receptor-TRAF2 interactions. TRADD is specific for TRAF1 and TRAF2, which ensures the recruitment of clAPs for the direct inhibition of caspase activation in the signaling complex. The stronger affinity and unique specificity of the TRADD-TRAF2 interaction are crucial for the suppression of apoptosis and provide a mechanistic basis for the perturbation of TRAF recruitment in sensitizing cell death induction.

Amino Acid Sequence↗
PubMed2000

Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-alpha secretion, and NF-kappaB-dependent gene expression in RAW 264.7 macrophages.

Flavonoids are potent antioxidants and have been associated with lowering the risk of cardiovascular diseases. In this study, the effect of flavonoids (monomers, dimers and a trimer) as well as French maritime pine bark extract, Pycnogenol, on NO production, tumor necrosis factor-alpha (TNF-alpha) secretion and nuclear factor (NF)-kappaB activity was compared. Monomers and dimers repressed NO production, TNF-alpha secretion and NF-kappaB-dependent gene expression induced by interferon gamma, whereas the trimeric procyanidin C2 and Pycnogenol enhanced these parameters. In addition, in unstimulated RAW 264.7 macrophages, both procyanidin C2 and Pycnogenol increased TNF-alpha secretion in a concentration- and time-dependent manner. These results demonstrate that procyanidins act as modulators of the immune response in macrophages.

Animals↗
PubMed2000

A convenient method for oxidation of organophosphorus pesticides in organic solvents.

Since organophosphorus pesticides can be oxidized to oxons in vivo and in the environment and their determination based on inhibition of cholinesterases can be more sensitive after their oxidation to oxons, development of an efficient method for their in vitro oxidation is important for their toxicological and analytical studies. This study demonstrated that treatment of organophosphorus pesticides with 10 molar excess bromine in acetonitrile is a rapid and efficient method for their oxidation. For the nine organophosphorus pesticides tested, the reaction was complete within a few seconds. All reactions gave the respective oxons as single major product, except that of fenthion, which gave two major products, the respective oxon and another product from further oxidation of the oxon. The yields of the oxons were 82-100%. The inhibitory power of the pesticides on acetylcholinesterase before and after oxidation was measured and, for all pesticides tested, the power after oxidation was much higher than that before oxidation. Inhibition calibration curves for both unoxidized and oxidized forms of fenitrothion and parathion were obtained. The sensitivity of the detection of these pesticides was much higher after oxidation.

Environmental Pollutants↗
PubMed2000

Children's experience of violence in China and Korea: a transcultural study.

OBJECTIVE: There were two aims: First, to compare children's rates of being battered in home, by peers, and by teachers among students between China and Korea, and second, to identify particular risk factors for such violence. METHODS: Children in grades four through six in Shanghai (238 cases) and Yanji (245 cases) in China and Seoul (248 cases) and Kimpo (241 cases) in Korea were surveyed by questionnaire method. They were asked to complete the Straus' Conflict Tactics Scale and their frequencies in the three situations respectively, and other demographic items. RESULTS: Family violence during the last 1 year was experienced in 70.6% (minor 42.2%; serious 22.6%) of the children in China and 68.9% (minor 9.4%; serious 51.3%) of those in Korea. Experience rates of violence by peers were 42.7% (minor 25.7%; serious 13.7%) in China and 26.0% (minor 11.5%; serious 14.3%) in Korea. Finally, rates of corporal punishment by teachers were 51.1% (minor 28.0%; serious 4.1%) in China and 62.0% (minor 8.8%; serious 43.8%) in Korea. The most important and common risk factor for violence in one situation was the presence of violence in another situation. CONCLUSIONS: The findings indicate that the differences in children's overall experience rates were not particularly striking. However, Korean children experienced more severe forms of violence from family members and from teachers. Findings of risk factors clearly imply that there are children vulnerable to violence from multiple sources.

Child↗
PubMed2000

Bioconversion of D-galactose into D-tagatose by expression of L-arabinose isomerase.

D-Tagatose is a potential bulking agent in food as a non-calorific sweetener. To produce D-tagatose from cheaper resources, plasmids harbouring the L-arabinose isomerase gene (araA) from Escherichia coli, Bacillus subtilis and Salmonella typhimurium were constructed because L-arabinose isomerase was suggested previously as an enzyme that mediates the bioconversion of galactose into tagatose as well as that of arabinose to ribulose. The constructed plasmids were named pTC101, pTC105 and pTC106, containing araA from E. coli, B. subtilis and S. typhimurium respectively. In the cultures of recombinant E. coli with pTC101, pTC105 and pTC106, tagatose was produced from galactose in 9.9, 7.1 and 6.9% yields respectively. The enzyme extract of E. coli with the plasmid pTC101 also converted galactose into tagatose with a 96.4% yield.

Aldose-Ketose Isomerases↗
PubMed2000

[A study of the clinical effect of estradiol transdermal therapeutic system alone on pollakisuria and urinary incontinence in postmenopausal woman].

PURPOSE: Our purpose of this study was to evaluate the effect of a transdermal estradiol delivery system in postmenopausal women with confirmed pollakisuria and urinary incontinence. PATIENTS AND METHODS: We investigated 10 postmenopausal women, age 54-83 years, with pollakisuria and urinary incontinence but did not show distinct urological and/or neurological abnormalities. In this study, estradiol transdermal therapeutic system (Estraderm TTS 2 mg) alone were administrated for total of 8-week and this is observational, not randomized, blinded or controlled. A clinical evaluation were performed two times at before and after administration. RESULTS: In seven eligible cases, the severity of urinary incontinence was graded down in almost of them and the therapeutic effect on urinary incontinence was evaluated as "very effective" in 3 cases, "improved" in 2, "slightly improved" in 1 and "no change" in 1, respectively. In three eligible cases, the severity of pollakisuria was no change in all of them. CONCLUSION: Thus, the estrogen supplement therapy was considered effective for postmenopausal urinary incontinence.

Administration, Cutaneous↗
PubMed2000

Effects of beta-adrenergic stimulation on the acutely obstructed ureter in dogs.

The objective of the present study was to evaluate the effects of a selective beta(3)-adrenoceptor agonist, (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate (CL 316243), on the acutely obstructed ureter in anesthetized dogs. After a complete ureteral obstruction produced by the inflation of a balloon catheter placed within the left lower ureter, the intraluminal ureteral pressure gradually rose to reach a plateau of approximately 52.5 mm Hg. Intravenous administration of isoproterenol (a nonselective beta-adrenoceptor agonist; 10 microg/kg) and CL 316243 (1 microg/kg) significantly decreased this elevated ureteral pressure (by 74.1 and 77.2%, respectively), with the reduction more sustained with CL 316243 than with isoproterenol. In addition, under both isoproterenol and CL 316243, urine flow (which had been interrupted by the balloon) was resumed, resulting in further sustained decreases in ureteral pressure. The mean blood pressure decreased and heart rate increased after the administration of both drugs, but these changes were greater in the isoproterenol group than in the CL 316243 group. In contrast, i.v. administration of butylscopolamine (an anticholinergic agent; 1000 microg/kg) had no evident effects on ureteral pressure or on urine flow. The increase in left kidney weight seen after ureteral obstruction was suppressed by CL 316243. We conclude that the selective beta(3)-adrenoceptor agonist tested appears to be more useful than isoproterenol for reducing ureteral pressure above the obstructed site and for promoting ureteral relaxation and increasing urine flow around the point of obstruction in dogs.

Adrenergic beta-Agonists↗
PubMed2000

Existence of a beta3-adrenoceptro and its functional role in the human ureter.

PURPOSE: We tried to determine the beta-adrenoceptor (AR) subtypes distributed in the human ureter and to clarify their functional role in ureteral relaxation. MATERIALS AND METHODS: 1) Effects of beta-AR agonists on either spontaneous or KCl-induced contractions of the human ureter and the antagonism by beta-AR antagonists on isoprenaline (a non-selective beta-AR agonist)-induced effects were evaluated in vitro. 2) Displacement by beta-AR antagonists of [3H]-dihydroalprenolol binding to a membrane preparation derived from human ureteral smooth muscle was evaluated. 3) A reverse transcription polymerase chain reaction assay was performed to determine the expression of the mRNA for beta1-, beta2- and beta3-ARs in human ureteral smooth muscle. RESULTS: 1) Isoprenaline and procaterol (a beta2-AR agonist) concentration-dependently suppressed both spontaneous and KCl-induced contractions of the human ureter. The beta3-AR agonists, CGP-12177A and CL-316243, also suppressed these ureteral contractions, but dobutamine (a beta1-AR agonist) had little relaxing effect. The rank order of relaxing potency for the catecholamines was isoprenaline > adrenaline > noradrenaline. ICI-118,551 (a beta2-AR antagonist) only partially antagonized the isoprenaline-induced relaxation. 2) Propranolol (a non-selective beta-AR antagonist) and ICI-118,551 concentration-dependently displaced [3H]-dihydroalprenolol binding to the membrane with Ki values of 1.5 x 10-9 M and 6.3 x 10-9 M, respectively, while metoprolol (a beta1-AR antagonist) was less effective in this assay. 3) beta1-, beta2- and beta3-AR mRNAs were all expressed in human ureteral smooth muscle. CONCLUSION: The present results provide the first evidence that the beta3-AR subtype is distributed in human ureteral smooth muscle and that it, and beta2-AR, mediate the ureteral relaxation induced by adrenergic stimulation.

Adult↗
PubMed1999

Structural basis for self-association and receptor recognition of human TRAF2.

Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. They are important in the regulation of cell survival and cell death. The carboxy-terminal region of TRAFs (the TRAF domain) is required for self-association and interaction with receptors. The domain contains a predicted coiled-coil region that is followed by a highly conserved TRAF-C domain. Here we report the crystal structure of the TRAF domain of human TRAF2, both alone and in complex with a peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self-association of the TRAF domain, which we confirm by studies in solution. The TRAF-C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C domain and does not contact the other protomers of the trimer. The nature of the interaction indicates that an SXXE motif may be a TRAF2-binding consensus sequence. The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands.

Amino Acid Sequence↗
PubMed1999

Experimental evolution of a dense cluster of residues in tyrosyl-tRNA synthetase: quantitative effects on activity, stability and dimerization.

A dense cluster of eight residues was identified at the crossing of two alpha-helices in tyrosyl-tRNA synthetase (TyrRS) from the thermophile Bacillus stearothermophilus. Its mechanism of evolution was characterized. Four residues of this cluster are not conserved in TyrRS from the mesophile Escherichia coli. The corresponding mutations were constructed in TyrRS(Delta1), a derivative of TyrRS from B. stearothermophilus in which the anticodon binding domain is deleted. Mutations I52L (i.e. Ile52 into Leu), M55L and L105V did not affect the activity of TyrRS(Delta1) in the pyrophosphate exchange reaction whereas T51P increased it. The kinetic stabilities of TyrRS(Delta1) and its mutant derivatives at 68.5 degreesC were determined from experiments of irreversible thermal precipitation. They were in the order L105V<I52L<T51P<Wild Type</=M55L; mutation I52L partially compensated L105V in these experiments whereas M55L was coupled neither to I52L nor to L105V. Mutations I52L and L105V affected the stability of the dimeric TyrRS(Delta1) at different steps of its unfolding by urea, monitored under equilibrium conditions by spectrofluorometry or size exclusion chromatography. I52L destabilized the association between the subunits even though residue Ile52 is more than 20 A away from the subunit interface. L105V destabilized the monomeric intermediate of unfolding. The two mutational pathways, going from the wild-type TyrRS(Delta1) to the I52L-L105V double mutant through each of the single mutants were not equivalent for the stability of the monomeric intermediate and for the total stability of the dimer. One pathway contained two neutral steps whereas the other pathway contained a destabilizing step followed by a stabilizing step. Mutation I52L allowed L105V along the first pathway and compensated it along the second pathway. Thus, the effects of I52L and L105V on stability depended on the structural context. The gain in activity due to T51P was at the expense of a slight destabilization.

Amino Acid Substitution↗
PubMed1999

Oxybutynin disrupts learning and memory in the rat passive avoidance response.

BACKGROUND: oxybutynin, a drug for pollakisuria and urinary incontinence, has a potent antimuscarinic activity. This study was aimed to determine whether this drug disrupts learning and memory in rats, because antimuscarinic activity in the central nervous system is considered to cause amnesia in humans. METHODS: male Wistar rats were given oxybutynin or scopolamine as a reference drug, and subjected to the acquisition trial of step-through passive avoidance response (PAR). Twenty-four hours later the retention test for each rat was performed and the latency time in the PAR was measured. RESULTS: oral administration of oxybutynin at 30 mg/kg or higher and intraperitonial injection of scoplamine at 0.5 mg/kg caused a significant decrease in the latency time in the retention test. CONCLUSIONS: oxubutynin caused a decrease in the retention time of the PAR in a manner similar to scopolamine, indicating that oxybutynin may cause disruption of learning and memory.

Administration, Oral↗
PubMed1999

The structural basis for the recognition of diverse receptor sequences by TRAF2.

Many members of the tumor necrosis factor receptor (TNFR) superfamily initiate intracellular signaling by recruiting TNFR-associated factors (TRAFs) through their cytoplasmic tails. TRAFs apparently recognize highly diverse receptor sequences. Crystal structures of the TRAF domain of human TRAF2 in complex with peptides from the TNFR family members CD40, CD30, Ox40, 4-1BB, and the EBV oncoprotein LMP1 revealed a conserved binding mode. A major TRAF2-binding consensus sequence, (P/S/A/T)x(Q/E)E, and a minor consensus motif, PxQxxD, can be defined from the structural analysis, which encompass all known TRAF2-binding sequences. The structural information provides a template for the further dissection of receptor binding specificity of TRAF2 and for the understanding of the complexity of TRAF-mediated signal transduction.

Amino Acid Sequence↗
PubMed1999

Heat shock and 5-azacytidine inhibit nitric oxide synthesis and tumor necrosis factor-alpha secretion in activated macrophages.

To elucidate the role of stress response during macrophage activation, the effects of heat shock and the amino acid analog, 5-azacytidine on nitric oxide (NO) production, tumor necrosis factor-alpha (TNF-alpha) secretion, and heat shock protein (HSP) synthesis have been studied in murine peritoneal macrophages (C57BL/6). Heat shock (1 hr at 43 degrees C) or 5-azacytidine markedly inhibited the release of NO into the medium from interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS)-stimulated macrophages. Although heat shock significantly decreased TNF-alpha secretion only at the initiation stage of macrophage stimulation, 5-azacytidine treatment resulted in a more prolonged reduction in the secretion of TNF-alpha. When heat-shocked cells were stimulated with IFN-gamma plus LPS under normal culture conditions at 37 degrees C, the heat shock-induced inhibition of NO release reversed progressively with increasing recovery time. Although the total amount of cellular HSP72 measured by Western blot increased time-dependently over 7 hr, newly synthesized HSP72 measured by [35S]methionine incorporation was evident only after 1 and 3 hr of recovery time after heat shock treatment. At these time points, the lowest nitrite accumulation and TNF-alpha secretion into the medium was evident. It is concluded that signaling pathways related to newly synthesized HSP such as HSP72 are implicated in the down regulation of NO synthesis and TNF-alpha secretion in macrophages.

Animals↗
PubMed1999

Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. TLC C-53 ARDS Study Group.

OBJECTIVE: To evaluate the safety and efficacy of an intravenous liposomal dispersion of prostaglandin E1 as TLC C-53 in the treatment of patients with acute respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled, phase III clinical trial. SETTING: Forty-seven community and university-affiliated hospitals in the United States. PATIENTS: A total of 350 patients with ARDS were enrolled in this clinical trial. INTERVENTION: Patients were prospectively randomized in a 1:1 ratio to receive either liposomal prostaglandin E1 or placebo. The study drug was infused intravenously for 60 mins every 6 hrs for 7 days starting with a dosage of 0.15 microg/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 microg/kg/hr) was attained or intolerance to further increases developed. Patients received standard aggressive medical/surgical care during the infusion period. OUTCOME MEASURES: The primary outcome measure was the time it took to wean the patient from the ventilator. Secondary end points included time to improvement of the PaO2/FIO2 ratio (defined as first PaO2/FIO2 > 300 mm Hg), day 28 mortality, ventilator dependence at day 8, changes in PaO2/FIO2, incidence of and time to development/resolution of organ failure other than ARDS. RESULTS: A total of 348 patients could be evaluated for efficacy. The distribution of variables at baseline describing gender, lung injury scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS or from institution of mechanical ventilation to the first dose of study drug was similar among patients in the liposomal prostaglandin E1 (n = 177) and the placebo (n = 171) treatment arms. There was no significant difference in the number of days to the discontinuation of ventilation in the liposomal prostaglandin E1 group compared with the placebo group (median number of days to off mechanical ventilation, 16.9 in patients receiving liposomal prostaglandin E1 and 19.6 in those administered placebo; p = .94). Similarly, mortality at day 28 was not significantly different in the two groups (day 28 mortality, 57 of 176 (32%) in the liposomal prostaglandin E1 group and 50 of 170 (29%) in patients receiving placebo; p = .55). In contrast, treatment with liposomal prostaglandin E1 was associated with a significantly shorter time to reach a PaO2/FIO2 ratio of >300 mm Hg (median number of days to reaching a PaO2/FIO2 ratio >300 mm Hg: 9.8 days in the liposomal prostaglandin E1 group and 13.7 days in patients receiving the placebo; p = .02). Among the subgroups examined, time to off mechanical ventilation was significantly reduced in patients who received at least 85% of a full dose (i.e., > 45.9 microg/kg) of liposomal prostaglandin E1 (median number of days to discontinuation of ventilation, 10.3 in the liposomal prostaglandin E1 group and 16.3 days in patients receiving placebo; p = .05). The overall incidence of serious adverse events was not significantly different in the liposomal prostaglandin E1 (40%) or placebo-treated (37%) groups. Drug-related adverse events of all kinds were reported in 69% of the patients receiving liposomal prostaglandin E1 compared with 33% of the placebo group, with hypotension and hypoxia (occurring in 52% and 24% of the liposomal prostaglandin E1-treated patients, respectively, and 17% and 5% of the placebo-treated patients, respectively) being noted most frequently. CONCLUSIONS: In the intent-to-treat population of patients with ARDS, treatment with liposomal prostaglandin E1 accelerated improvement in indexes of oxygenation but did not decrease the duration of mechanical ventilation and did not improve day 28 survival.

Adult↗
PubMed1999

Chloroquine inhibits inducible nitric oxide synthase expression in murine peritoneal macrophages.

Induction of inducible nitric oxide synthase in vivo or in vitro in response to stimuli is only temporary. However, chronic localized expression of inducible nitric oxide synthase in certain organs has been associated with the development of autoimmune diseases or chronic inflammatory diseases. Chloroquine is being used as an antiinflammatory drug, and its inhibitory effect on the synthesis of pro-inflammatory cytokines, such as tumour necrosis factor-alpha and interferon-gamma, has been reported. In this study, we examined whether chloroquine could inhibit nitric oxide synthesis in murine peritoneal macrophages stimulated with interferon-gamma and lipopolysaccharide. Although prolonged incubation of cells with high concentrations of chloroquine showed some cytotoxicity, the drug itself was not cytotoxic when macrophages were preincubated with chloroquine for 2 hr, washed and stimulated with interferon-gamma and lipopolysaccharide in the absence of chloroquine for another 48 hr. The nitric oxide production from stimulated macrophages was markedly reduced by chloroquine in a dose-dependent manner and induction of inducible nitric oxide synthase mRNA was also suppressed by chloroquine pretreatment. These results show that chloroquine inhibits the induction of inducible nitric oxide synthase from interferon-gamma and lipopolysaccharide-stimulated macrophages, thereby reducing nitric oxide synthesis.

Animals↗