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Y W Lee

Publications and source records attributed to Y W Lee.

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

Modeling multivariate survival data by a semiparametric random effects proportional odds model.

In this article, the focus is on the analysis of multivariate survival time data with various types of dependence structures. Examples of multivariate survival data include clustered data and repeated measurements from the same subject, such as the interrecurrence times of cancer tumors. A random effect semiparametric proportional odds model is proposed as an alternative to the proportional hazards model. The distribution of the random effects is assumed to be multivariate normal and the random effect is assumed to act additively to the baseline log-odds function. This class of models, which includes the usual shared random effects model, the additive variance components model, and the dynamic random effects model as special cases, is highly flexible and is capable of modeling a wide range of multivariate survival data. A unified estimation procedure is proposed to estimate the regression and dependence parameters simultaneously by means of a marginal-likelihood approach. Unlike the fully parametric case, the regression parameter estimate is not sensitive to the choice of correlation structure of the random effects. The marginal likelihood is approximated by the Monte Carlo method. Simulation studies are carried out to investigate the performance of the proposed method. The proposed method is applied to two well-known data sets, including clustered data and recurrent event times data.

Animals↗
PubMed2002

Indoor thermal fogging against vector mosquitoes with two Bacillus thuringiensis israelensis formulations, Vectobac ABG 6511 water-dispersible granules and Vectobac 12AS liquid.

Bioefficacy of thermal fogging application of 2 Bacillus thuringiensis israelensis formulations, Vectobac ABG 6511 water-dispersible granules (3,000 international toxic unit [ITU]/mg) and Vectobac 12AS liquid (1,200 ITU/mg), was assessed for larvicidal activities against Aedes aegypti, Aedes albopictus, Anopheles dirus, and Culex quinquefasciatus. Portable Agrofog AF35 sprayers were used to apply the 2 formulations indoors in residential premises on Penang Island, Malaysia. Vectobac ABG 6511 showed good larvicidal effect against all 4 mosquito species at 3 of the higher doses tested (2.91 x 10(9), 1.45 x 10(9), and 0.71 x 10(9) ITU/ha), with more than 96% mortality at 48 h after spraying. As a comparative formulation, Vectobac 12AS also showed good larvicidal activity against all 4 mosquito species at 2 of the higher doses tested (2.87 x 10(9) and 1.46 x 10(9) ITU/ha), with more than 92.5% mortality at 48 h after spraying. Larvae of An. dirus were significantly more susceptible to both water-based Vectobac formulations when compared to the other 3 mosquito species. Both microbial formulations showed better efficacy at higher doses. However, even at the lowest dose tested, Vectobac ABG 6511 and Vectobac 12AS (both at 0.36 x 10(9) ITU/ha) showed larvicidal properties, with more than 66% mortality at 48 h after spraying. Overall, for this bacterial agent, the water-dispersible granule formulation has better prospects than the liquid formulation for the control of larvae of vector mosquitoes.

Aedes↗
PubMed2002

Comparison of phytotoxicity and mammalian cytotoxicity of nontrichothecene mycotoxins.

The phytotoxicity and mammalian cytotoxicity of four nontrichothecene mycotoxins (apicidin, sambutoxin, wortmannin, HC-toxin) were compared. Phytotoxicity was evaluated in terms of electrolyte leakage, growth inhibition, and reduction in chlorophyll content. Based on the parameters evaluated, the relative order of phytotoxicity to duckweed (Lemna pausicostata L.) was wortmannin > HC-toxin > apicidin >> sambutoxin. A 48-hr exposure to 10 microM wortmannin, HC-toxin or apicidin caused electrolyte leakage from duckweed. The IC50 values for growth inhibition and chlorophyll reduction for wortmannin, HC-toxin, and apicidin were 0.2 and 2.6 microM, 15.4 and 12.6 microM, and 27.7 and 45.3 microM, respectively. Based on the parameters measured, a 72-hr exposure to 100 microM sambutoxin was not toxic to duckweed. Kudzu (Pueraria lobata L.) leaf disc assays revealed a similar trend in relative toxicities, but higher mycotoxin concentrations were required to elicit phytotoxic effects compared to duckweed. All four mycotoxins were cytotoxic to four mammalian cell cultures. However, in contrast to plants, wortmannin was the least toxic (IC50 = 10 to 20 microM) and sambutoxin exhibited a high level of toxicity (IC50 = 0.5 to 1 microM).

Animals↗
PubMed2001

Cocaine activates redox-regulated transcription factors and induces TNF-alpha expression in human brain endothelial cells.

Cocaine abuse is frequently associated with cerebrovascular pathology. Although the cellular and molecular mechanisms of these alterations are not fully understood, they may involve oxidative injury or dysfunction of brain microvascular endothelial cells. To test this hypothesis, total glutathione levels, activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), as well as induction of the TNF-alpha gene expression were determined in human brain microvascular endothelial cells (HBMEC) exposed to cocaine. Exposure of HBMEC to cocaine resulted in a dose-dependent depletion of total glutathione levels. In addition, cocaine markedly activated redox-regulated transcription factors, NF-kappaB and AP-1. Activation of these transcription factors was accompanied by induction of AP-1- or NF-kappaB-dependent transcription, as measured by dual luciferase assay in HBMEC transfected with the AP-1- or NF-kappaB-responsive reporter constructs. Furthermore, HBMEC treatment with cocaine induced a dose-dependent expression of the tumor necrosis factor-alpha (TNF-alpha) gene. These results indicate that exposure to cocaine can trigger inflammatory pathways via activation of redox-sensitive transcription factors and induction of expression of the inflammatory genes in HBMEC. These events may contribute to the cerebrovascular insults observed in cocaine-abused patients.

Brain Chemistry↗
PubMed2001

Methamphetamine induces AP-1 and NF-kappaB binding and transactivation in human brain endothelial cells.

Cellular and molecular mechanisms of methamphetamine (METH)-induced neurotoxicity may involve alterations of cellular redox status and induction of inflammatory genes in endothelial cells. To study these hypotheses, molecular signaling pathways of METH-induced inflammatory responses via activation of redox-sensitive transcription factors were investigated in human brain microvascular endothelial cells (HBMEC). A dose-dependent depletion of total glutathione levels was detected in HBMEC exposed to METH. In addition, electrophoretic mobility shift assay (EMSA) showed significant increases in DNA binding activities of redox-responsive transcription factors, AP-1 and NF-kappaB, in HBMEC treated with METH. METH-mediated AP-1 or NF-kappaB activation was accompanied by induction of transactivation of AP-1 or NF-kappaB, as measured by dual luciferase assay using specific reporter plasmids. Because NF-kappaB and AP-1 are known to regulate expression of inflammatory genes, expression of the gene encoding for tumor necrosis factor-alpha (TNF-alpha) was also studied in METH-treated HBMEC. A dose-dependent overexpression of the TNF-alpha gene was observed in HBMEC treated with METH. The importance of AP-1 and NF-kappaB in METH-induced TNF-alpha gene was confirmed in functional promoter studies using constructs of the TNF-alpha promoter with mutated AP-1 or NF-kappaB sites. These results indicate that METH-induced disturbances in cellular redox status and activation of AP-1 and NF-kappaB can play critical roles in the signaling pathways leading to upregulation of inflammatory genes in human brain endothelial cells.

Amphetamine-Related Disorders↗
PubMed2001

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↗
PubMed2001

Design of null lenses for testing of elliptical surfaces.

Null lenses are designed for testing the oblate elliptical surface that is the third mirror of the off-axis three-mirror anastigmatic camera used for remote sensing. Modifying the conventional autostigmatic and autocollimation types of null lenses yields a mixed-type design that has a small annular flat mirror and high sensitivity. Detailed analyses of the sensitivity of the mixed-type null lens system with changes in each surface parameter are described.

Journal Article↗
PubMed2001

Jasmonic acid carboxyl methyltransferase: a key enzyme for jasmonate-regulated plant responses.

Methyl jasmonate is a plant volatile that acts as an important cellular regulator mediating diverse developmental processes and defense responses. We have cloned the novel gene JMT encoding an S-adenosyl-l-methionine:jasmonic acid carboxyl methyltransferase (JMT) from Arabidopsis thaliana. Recombinant JMT protein expressed in Escherichia coli catalyzed the formation of methyl jasmonate from jasmonic acid with K(m) value of 38.5 microM. JMT RNA was not detected in young seedlings but was detected in rosettes, cauline leaves, and developing flowers. In addition, expression of the gene was induced both locally and systemically by wounding or methyl jasmonate treatment. This result suggests that JMT can perceive and respond to local and systemic signals generated by external stimuli, and that the signals may include methyl jasmonate itself. Transgenic Arabidopsis overexpressing JMT had a 3-fold elevated level of endogenous methyl jasmonate without altering jasmonic acid content. The transgenic plants exhibited constitutive expression of jasmonate-responsive genes, including VSP and PDF1.2. Furthermore, the transgenic plants showed enhanced level of resistance against the virulent fungus Botrytis cinerea. Thus, our data suggest that the jasmonic acid carboxyl methyltransferase is a key enzyme for jasmonate-regulated plant responses. Activation of JMT expression leads to production of methyl jasmonate that could act as an intracellular regulator, a diffusible intercellular signal transducer, and an airborne signal mediating intra- and interplant communications.

Amino Acid Sequence↗
PubMed2001

Transcriptional activation of p21(WAF1/CIP1) by apicidin, a novel histone deacetylase inhibitor.

Apicidin [cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-l-2-amino-8-oxodecanoyl)], a novel histone deacetylase inhibitor, has been identified as an antiprotozoal and antiproliferative agent. In this study, we show apicidin induces transcriptional activation of p21(WAF1/CIP1) (p21) in human prostate carcinoma cells. Apicidin induces expression of p21 protein and mRNA and activation of p21 promoter-luciferase reporter constructs. Apicidin causes an accumulation of acetylated histones H3 and H4 in total cellular chromatin. Chromatin immunoprecipitation shows p21 promoter DNA is associated with hyperacetylated histones H3 and H4 after treatment with apicidin. Therefore, the data here demonstrate that apicidin activates p21 transcription associated with the acetylation of histones H3 and H4.

Acetylation↗
PubMed2001

IL-4-induced oxidative stress upregulates VCAM-1 gene expression in human endothelial cells.

Vascular cell adhesion molecule-1 (VCAM-1) is expressed in early stages of atherosclerosis; however, the mechanisms of its upregulation are not fully understood. In the present study, we examined the effects of interleukin-4 (IL-4) on VCAM-1 gene expression and its transcriptional regulatory mechanism in human umbilical vein endothelial cells (HUVEC). Reverse transcription-polymerase chain reaction showed that VCAM-1 mRNA was induced in IL-4-treated HUVEC in a time- and dose-dependent manner. Among known transcription factors that have binding sites in the promoter region of the VCAM-1 gene, IL-4 activated only SP-1. In contrast, nuclear factor- kappa B (NF- kappa B), activator protein-1 (AP-1) and interferon regulatory factor-1 (IRF-1), which also have consensus binding sequences in the 5'-flanking region of the human VCAM-1 gene, were not activated. The role of SP-1 in IL-4-induced VCAM-1 expression was confirmed in HUVEC transfected with a reporter construct of the VCAM-1 promoter with mutated SP-1 binding site. As IL-4 treatment of HUVEC enhanced the intracellular oxidizing potential, as indicated by an increase in 2',7'-dichlorofluorescein (DCF) fluorescence, we studied the effect of antioxidants on IL-4-induced VCAM-1 expression. Pretreatment of HUVEC with pyrrolidine dithiocarbamate (PDTC) or N-acetylcysteine (NAC) completely prevented IL-4-induced VCAM-1 expression. In addition, PDTC inhibited IL-4-related activation of SP-1. These results suggest that IL-4-induced oxidative stress upregulates the expression of VCAM-1 gene in HUVEC at transcriptional levels via activation of SP-1 transcription factor. In contrast, NF- kappa B, AP-1 or IRF-1 do not appear to be involved in the signal transduction cascade.

Acetylcysteine↗
PubMed2001

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↗
PubMed2001

Dynamic random effects models for times between repeated events.

We consider recurrent event data when the duration or gap times between successive event occurrences are of intrinsic interest. Subject heterogeneity not attributed to observed covariates is usually handled by random effects which result in an exchangeable correlation structure for the gap times of a subject. Recently, efforts have been put into relaxing this restriction to allow non-exchangeable correlation. Here we consider dynamic models where random effects can vary stochastically over the gap times. We extend the traditional Gaussian variance components models and evaluate a previously proposed proportional hazards model through a simulation study and some examples. Besides, semiparametric estimation of the proportional hazards models is considered. Both models are easily used. The Gaussian models are easily interpreted in terms of the variance structure. On the other hand, the proportional hazards models would be more appropriate in the context of survival analysis, particularly in the interpretation of the regression parameters. They can be sensitive to the choice of model for random effects but not to the choice of the baseline hazard function.

Animals↗
PubMed2001

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↗
PubMed2001

The value of contrast echocardiography in the diagnosis of patent ductus arteriosus with Eisenmenger's syndrome.

When patent ductus arteriosus (PDA) is complicated by pulmonary hypertension resulting in a right-to-left shunt, an erroneous diagnosis of primary pulmonary hypertension may be made, even after echocardiographic examination. Among the 8 patients referred to our echocardiography laboratory with the diagnosis of primary pulmonary hypertension between June 1994 and November 1999, 2 patients were found to have PDA with Eisenmenger's syndrome. Patent ductus arteriosus with Eisenmenger's syndrome can be diagnosed by the opacification of the abdominal aorta without opacification of the left-sided chambers during contrast echocardiography.

Adolescent↗
PubMed2001

Linoleic acid-induced VCAM-1 expression in human microvascular endothelial cells is mediated by the NF-kappa B-dependent pathway.

Vascular cell adhesion molecule-1 (VCAM-1) has been reported to play an important role in cancer metastasis via the adhesive interaction between tumor cells and endothelial cells. In this study, we examined the effects of linoleic acid on VCAM-1 expression and its transcriptional regulatory mechanism in human microvascular endothelial cells (HMEC-1). Time- and dose-dependent increases of VCAM-1 mRNA levels were observed in linoleic acid-treated HMEC-1 as detected by reverse transcriptase-polymerase chain reaction. Flow cytometry analysis showed a significant and dose-dependent upregulation of VCAM-1 expression in HMEC-1 stimulated with linoleic acid compared with controls. To clarify the transcriptional regulatory pathway, we investigated the role of nuclear factor-kappa B (NF-kappa B) in the expression of VCAM-1 by linoleic acid in HMEC-1. Nuclear extracts from HMEC-1 stimulated with linoleic acid showed a dose-dependent increase in binding activity to the NF-kappa B consensus sequences. These effects were preventable by cotreatment with inhibitors of NF-kappa B activity, such as sodium salicylate, aspirin, or pyrrolidine dithiocarbamate. In addition, pretreatment with NF-kappa B inhibitors markedly suppressed the ability of linoleic acid to induce VCAM-1 gene expression. The role of NF-kappa B in linoleic acid-induced VCAM-1 expression was confirmed by functional promoter studies in HMEC-1 transfected with reporter constructs of the VCAM-1 promoter with or without mutated NF-kappa B binding site. These results indicate that linoleic acid upregulates VCAM-1 expression in HMEC-1 through the NF-kappa B-dependent pathway.

Binding Sites↗
PubMed2001

Identification of deoxynivalenol- and nivalenol-producing chemotypes of Gibberella zeae by using PCR.

Gibberella zeae, a major cause of cereal scab, may be divided into two chemotypes based on production of the trichothecenes deoxynivalenol (DON) and nivalenol (NIV). We cloned and sequenced the gene cluster for trichothecene biosynthesis from each chemotype. G. zeae H-11 is a DON producer isolated from corn, and G. zeae 88-1 is a NIV producer from barley. We sequenced a 23-kb gene cluster from H-11 and a 26-kb cluster from 88-1, along with the unlinked Tri101 genes. Each gene cluster contained 10 Tri gene homologues in the same order and transcriptional directions as those of Fusarium sporotrichioides. Between H-11 and 88-1 all of the Tri homologues except Tri7 were conserved, with identities ranging from 88 to 98% and 82 to 99% at the nucleotide and amino acid levels, respectively. The Tri7 sequences were only 80% identical at the nucleotide level. We aligned the Tri7 genes and found that the Tri7 open reading frame of H-11 carried several mutations and an insertion containing 10 copies of an 11-bp tandem repeat. The Tri7 gene from 88-1 carried neither the repeat nor the mutations. We assayed 100 G. zeae isolates of both chemotypes by PCR amplification with a primer pair derived from the Tri7 gene and could differentiate the chemotypes by polyacrylamide gel electrophoresis. The PCR-based method developed in this study should provide a simple and reliable diagnostic tool for differentiating the two chemotypes of G. zeae.

Cloning, Molecular↗