Lee Jie - Academia.edu (original) (raw)

Papers by Lee Jie

Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identified in Kaposi's sarcoma and... more Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identified in Kaposi's sarcoma and body cavity-based lymphoma. KSHV encodes a transforming protein called K1 which is structurally similar to lymphocyte receptors. We have found that a highly conserved region of the cytoplasmic domain of K1 resembles the sequence of immunoreceptor tyrosine-based activation motifs (ITAMs). To demonstrate the signal-transducing activity of K1, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8␣ polypeptide was replaced with that of KSHV K1. Expression of the CD8-K1 chimera in B cells induced cellular tyrosine phosphorylation and intracellular calcium mobilization upon stimulation with an anti-CD8 antibody. Mutational analyses showed that the putative ITAM of K1 was required for its signal-transducing activity. Furthermore, tyrosine residues of the putative ITAM of K1 were phosphorylated upon stimulation, and this allowed subsequent binding of SH2-containing proteins. These results demonstrate that the KSHV transforming protein K1 contains a functional ITAM in its cytoplasmic domain and that it can transduce signals to induce cellular activation.

European Journal of Pharmacology, 2006

The intracellular mechanisms underlying the signaling pathways of activated matrix metalloprotein... more The intracellular mechanisms underlying the signaling pathways of activated matrix metalloproteinase-9 (MMP-9) in platelets are not yet completely understood. Therefore, the aim of this study was to further examine the effects of activated MMP-9 in preventing platelet aggregation. In this study, activated MMP-9 time-dependently (3–60 min) inhibited platelet aggregation in washed human platelet suspensions stimulated by agonists. However, activated MMP-9 had no significant effect on the binding of FITC-triflavin to the platelet glycoprotein IIb/IIIa complex. Triflavin is a specific antagonist of the glycoprotein IIb/IIIa complex purified from snake venom. Moreover, activated MMP-9 (21 and 90 ng/ml) markedly decreased the fluorescence intensity of platelet membranes tagged with diphenylhexatriene. The thrombin-evoked increase in pHi was inhibited in the presence of activated MMP-9 (21 and 90 ng/ml). In addition, activated MMP-9 (21 and 90 ng/ml) markedly reduced the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 μg/ml)-activated platelets. These results indicate that the antiplatelet activity of activated MMP-9 may involve the following pathways: (1) activated MMP-9 may initially induce conformational changes in platelet membranes and hydroxyl radical formation, leading to inhibition of platelet aggregation; and (2) activated MMP-9 also inhibits the Na+/H+ exchanger, leading to reduced intracellular Ca2+ mobilization, and ultimately to inhibition of platelet aggregation. This study further provides new insights concerning the effects of activated MMP-9 on platelet aggregation.

Febs Letters, 2006

To investigate a role for histidine residues in the expression of normal acyl-CoA:cholesterol acy... more To investigate a role for histidine residues in the expression of normal acyl-CoA:cholesterol acyltransferase (ACAT) activity, the histidine residues located at five different positions in two isoenzymes were substituted by alanine, based on the sequence homology between ACAT1 and ACAT2. Among the 10 mutants generated by baculovirus expression technology, H386A–ACAT1, H460A–ACAT1, H360A–ACAT2, and H399A–ACAT2 lost their enzymatic activity completely. A reduction in catalytic activity is unlikely to result from structural changes in the substrate-binding pocket, because their substrate-binding affinities were normal. However, the enzymatic activity of H386A–ACAT1 was restored to <37% of the level of the wild-type activity when cholesterol was replaced by 25-hydroxycholesterol as substrate. H527A–ACAT1 and H501A–ACAT2, termed carboxyl end mutants, exhibit activities of ∼96% and ∼75% of that of the wild-type. Interestingly, H425A–ACAT1 showed 59% of the wild-type activity, in contrast to its equivalent mutant, H399A-ACAT2. These results demonstrate that the histidine residues located at the active site are very crucial both for the catalytic activity of the enzyme and for distinguishing ACAT1 from ACAT2 with respect to enzyme catalysis and substrate specificity.

As the complexity of the requirements for advanced traveler information systems (ATIS) continues ... more As the complexity of the requirements for advanced traveler information systems (ATIS) continues to grow, the research towards better and faster development of ATIS is gaining increasing attentions. However, two issues on the delivery of services remain to be addressed: 1) how to quickly build a flexible ATIS to incorporate services that reside in the extant software; and 2) how to perform complex services on the devices of limited resources like on-board PCs. In this paper, we propose a service delivery mechanism based on Web services and agent technology to alleviate these issues. Based on the proposed mechanism, a flexible and extensible ATIS can be developed and its services can be delivered in a systematic manner.

Neuroreport, 2006

The present study investigates the e¡ects of neighborhood size and neighborhood frequency in read... more The present study investigates the e¡ects of neighborhood size and neighborhood frequency in reading Chinese two-character words. The neighborhood size of a word is de¢ned as the summation of neighbors sharing the ¢rst constituent (neighborhood size 1) and the second constituent (neighborhood size 2) characters. The ¢rst experiment found two opposite neighborhood size e¡ects in lexical decision of high-frequency and low-frequency words. The regression analysis showed that neighborhood size 1 in£uenced word reading more than the neighborhood size 2. The second experiment con¢rmed this ¢nding and showed that reading words with higher frequency neighbors took a longer time and elicited greater N400 and LPC than those without higher frequency neighbors. These ¢ndings indicate that, when reading Chinese two-character words, all words sharing the ¢rst constituent character are activated in the early stage of word recognition and the existence of highfrequency words among neighbors leads to greater competition in the stage of semantic integration and response selection. NeuroReport17:1061^1065

Journal of Medical Virology, 2010

Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC strain has c... more Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 07_BC strain has caused serious outbreaks among injection drug users in Taiwan since 2004. The objective of this study was to conduct a molecular epidemiological study of HCV genotypes in intravenous drug users in Taiwan. Blood samples and questionnaires from 591 intravenous drug users infected with HIV-1 were collected nationwide. In total, 180 samples were selected for HCV genotyping using multiplex PCR and phylogenetic analysis of the core, E1 and NS5B regions. The Inno-Lipa assay was used to confirm multiple infections with different genotypes. Eighty percent had a single infection with subtype 1b being the most common subtype (24%), 12% had double infections and two had triple infections. In addition, three recombinant forms (RFs)-2a1a, 3a1b, and 2b6w were identified. Phylogenetic analyses showed that the 3a, 6a, and 6n strains were clustered with strains present in Thailand and mainland China. Full-length sequence analysis showed that two 6w strains shared 89.4–90.2% sequence homology with the 6(r) strain from the Guangdong Province, China. Bootscan analysis revealed that the recombination breakpoint of RF_2b6w was located at the NS2-NS3 junction. In summary, the distribution of HCV genotypes among Taiwanese intravenous drug users was complex and more than 12% of the drug users were infected with more than one genotype of HCV. J. Med. Virol. 82:57–68, 2010. © 2009 Wiley-Liss, Inc.

The notion of organizations is getting increasing attentions for building open multi-agent system... more The notion of organizations is getting increasing attentions for building open multi-agent systems by mimicking the collaboration of human beings for achieving the organization objectives. However, there is little support in the existing approaches to dealing with the issues of dynamic role binding towards building an agent organization in which roles and agents are designed by different designers. The main

Advances in Developing Human Resources, 2006

The problem and the solution. As a transitioning society in the developing world, Morocco has mad... more The problem and the solution. As a transitioning society in the developing world, Morocco has made significant progress in improving human development and social conditions and has recently introduced a number of reforms that are intended to promote human rights and economic ...

Sid Symposium Digest of Technical Papers, 2007

As open multi-agents systems are getting increasing attentions in building large-scale software s... more As open multi-agents systems are getting increasing attentions in building large-scale software systems, the study on agent organizations - a building block of multi-agents systems, becomes a promising research track. Roles as a first class citizen in agent organizations impose an imperious demand for dealing with the major challenge: how agents bind roles in the formation of agent organizations in

Journal of Surgical Oncology, 2009

Background and ObjectivesSeveral studies have reported controversial results about clinicopatholo... more Background and ObjectivesSeveral studies have reported controversial results about clinicopathological features and prognoses in gastric cancer patients with respect to age, partly due to variable definitions of young age and inhomogeneity of the patient population. The aim of study was to analyze clinicopathological features and prognostic value of all stages of gastric cancer in a large consecutive series.Several studies have reported controversial results about clinicopathological features and prognoses in gastric cancer patients with respect to age, partly due to variable definitions of young age and inhomogeneity of the patient population. The aim of study was to analyze clinicopathological features and prognostic value of all stages of gastric cancer in a large consecutive series.MethodsBetween 2000 and 2005, 3,362 patients with all stages of gastric cancer were enrolled in database. Patients were divided into three groups: group 1 (≤45), group 2 (46–70), and group 3 (≥71).Between 2000 and 2005, 3,362 patients with all stages of gastric cancer were enrolled in database. Patients were divided into three groups: group 1 (≤45), group 2 (46–70), and group 3 (≥71).ResultsUpper location and linitis plastica were more frequent in group 1. Young patients had a higher proportion of poorly differentiated and signet ring cell type with elevated CA19-9 level. Depressed type was more frequent in early gastric cancer (EGC) while Bormann type IV and Lauren diffuse type were more common in AGC in group 1. In curatively resected patients, a 5-year survival rate was significantly higher in group 1 than older groups. Stage, vein invasion, curative resection, and CA19-9 level were significant prognostic factors in all gastric cancer.Upper location and linitis plastica were more frequent in group 1. Young patients had a higher proportion of poorly differentiated and signet ring cell type with elevated CA19-9 level. Depressed type was more frequent in early gastric cancer (EGC) while Bormann type IV and Lauren diffuse type were more common in AGC in group 1. In curatively resected patients, a 5-year survival rate was significantly higher in group 1 than older groups. Stage, vein invasion, curative resection, and CA19-9 level were significant prognostic factors in all gastric cancer.ConclusionsClinicopathological features associated with young gastric cancer include upper location, linitis plastica, histopathologically diffuse type, and unresectability. J. Surg. Oncol. 2009;99:395–401. © 2009 Wiley-Liss, Inc.Clinicopathological features associated with young gastric cancer include upper location, linitis plastica, histopathologically diffuse type, and unresectability. J. Surg. Oncol. 2009;99:395–401. © 2009 Wiley-Liss, Inc.

Journal of Allergy and Clinical Immunology, 2008

Activation of mast cells through the high-affinity receptor for IgE (FcepsilonRI) underlies atopi... more Activation of mast cells through the high-affinity receptor for IgE (FcepsilonRI) underlies atopic allergic reactions. Curcumin can block this activation, but the mechanism and the effects of curcumin on IgE-mediated allergic reactions are unknown. We sought to determine the antiallergic activity of curcumin in vivo and its mechanism of action in mast cells. The antiallergic activity of curcumin was evaluated in mast cell cultures and the passive cutaneous anaphylaxis model. The effects of curcumin on mast cell signaling events were examined by using immunoblotting, immunoprecipitation, RT-PCR, and other molecular biologic approaches. Curcumin inhibited antigen-mediated activation of mast cells and passive cutaneous anaphylaxis in mice. Suppression of degranulation and secretion of TNF-alpha and IL-4 was apparent at concentrations as low as 3 micromol/L curcumin in activated mast cells. Similar concentrations of curcumin suppressed Syk-dependent phosphorylations of the adaptor proteins linker of activated T cells and Grb2-associated binder 2, which are critical for mast cell activation. Although curcumin did not inhibit the phosphorylation of Syk itself, it directly inhibited Syk kinase activity in vitro. Further downstream, activating phosphorylations of Akt and the mitogen-activated protein kinases p38, p44/42 (extracellular signal-regulated kinase 1/2), and c-Jun N-terminal kinase, which are critical for the production of inflammatory cytokines, were also inhibited. Curcumin inhibits Syk kinase-dependent signaling events in mast cells and might thus contribute to its antiallergic activity. Therefore curcumin might be useful for the treatment of mast cell-related immediate and delayed allergic diseases.

Annals of Biomedical Engineering, 2010

This study presents a new steady-state visual evoked potential (SSVEP)-based brain computer inter... more This study presents a new steady-state visual evoked potential (SSVEP)-based brain computer interface (BCI). SSVEPs, induced by phase-tagged flashes in eight light emitting diodes (LEDs), were used to control four cursor movements (up, right, down, and left) and four button functions (on, off, right-, and left-clicks) on a screen menu. EEG signals were measured by one EEG electrode placed at Oz position, referring to the international EEG 10-20 system. Since SSVEPs are time-locked and phase-locked to the onsets of SSVEP flashes, EEG signals were bandpass-filtered and segmented into epochs, and then averaged across a number of epochs to sharpen the recorded SSVEPs. Phase lags between the measured SSVEPs and a reference SSVEP were measured, and targets were recognized based on these phase lags. The current design used eight LEDs to flicker at 31.25 Hz with 45° phase margin between any two adjacent SSVEP flickers. The SSVEP responses were filtered within 29.25–33.25 Hz and then averaged over 60 epochs. Owing to the utilization of high-frequency flickers, the induced SSVEPs were away from low-frequency noises, 60 Hz electricity noise, and eye movement artifacts. As a consequence, we achieved a simple architecture that did not require eye movement monitoring or other artifact detection and removal. The high-frequency design also achieved a flicker fusion effect for better visualization. Seven subjects were recruited in this study to sequentially input a command sequence, consisting of a sequence of eight cursor functions, repeated three times. The accuracy and information transfer rate (mean ± SD) over the seven subjects were 93.14 ± 5.73% and 28.29 ± 12.19 bits/min, respectively. The proposed system can provide a reliable channel for severely disabled patients to communicate with external environments.

International Journal of Dermatology, 2001

AbstractBackground Melanocyte number and the amount of melanin pigment are related to diagnosis ... more AbstractBackground Melanocyte number and the amount of melanin pigment are related to diagnosis and treatment of pigmentary skin diseases. Various histologic methods are used, such as Fontana-Masson stain for melanin pigment or immunohistochemical stain for melanocytes. Recently, computerized image analysis has been applied to many fields to avoid interobserver bias. In this study, we applied a computerized image analysis to assess the melanin content and melanocyte density of human epidermis.Methods We evaluated the skin biopsy specimens (paraffin blocks) from normal human skin (33 ± 6.6, n = 11) and diseased skins; vitiligo (32 ± 10.0, n = 8), melasma (35 ± 8.6, n = 11), and lentigo senilis (40 ± 7.2, n = 11) (mean age ± SD). Each specimen was stained with Fontana–Masson for melanin pigments and immunohistochemical method for melanocytes. Quantitative analysis of melanin pigment and melanocyte number (density) were investigated through two methods: (1) two dermatologists measured the visual scales; and (2) computerized image analysis was used to measure melanin content indices (MCI). The data were evaluated using one-way anova.Results The visual scale of the Fontana–Masson stain was the highest for lentigo senilis (3.8 ± 0.40), followed by melasma (2.6 ± 0.67), normal skin (1.8 ± 0.60) and vitiligo (0) (P < 0.05). These findings were consistent with objective measurements made by computerized image analysis. MCI values were 120.3 ± 20.74 for lentigo senilis, 81.1 ± 19.27 for melasma, 45.5 ± 16.92 for normal skin, and 0.3 ± 0.30 for vitiligo in decreasing order (P < 0.05). MC/1E (melanocyte number per 1 mm epidermis) was about two fold larger in lentigo senilis (18.1 ± 8.92) than melasma (9.7 ± 2.40) or normal skin (9.3 ± 2.67) (P < 0.05). MC/1B (melanocyte number per 1 mm basal layer) was about 1.5 fold higher in lentigo senilis (13.5 ± 4.17), compared to normal skin (9.0 ± 3.55) (P < 0.05). Melasma showed increased melanocyte numbers compared to normal skin, but it was not statistically significant (P > 0.05).Conclusion We believe this computerized image analysis could be useful tool for diagnosis and comparison of interval changes in pigmentary diseases like melasma or lentigo senilis by quantifying melanin pigments or melanocytes in skin biopsy specimens.

Febs Letters, 2003

Angiotensin I-converting enzymes (ACEs) are zinc metallopeptidases that cleave carboxy-terminal d... more Angiotensin I-converting enzymes (ACEs) are zinc metallopeptidases that cleave carboxy-terminal dipeptides from short peptide hormones. We have determined the crystal structures of AnCE, a Drosophila homolog of ACE, with and without bound inhibitors to 2.4 A î resolution. AnCE contains a large internal channel encompassing the entire protein molecule. This substrate-binding channel is composed of two chambers, reminiscent of a peanut shell. The inhibitor and zinc-binding sites are located in the narrow bottleneck connecting the two chambers. The substrate and inhibitor speci¢city of AnCE appears to be determined by extensive hydrogen-bonding networks and ionic interactions in the active site channel. The catalytically important zinc ion is coordinated by the conserved Glu395 and histidine residues from a HExxH motif. ß

Journal of Clinical Investigation, 2000

Cell Transplantation, 2009

Abstract: A number of emerging tools…

Nature, 2009

The lipopolysaccharide (LPS) of Gram negative bacteria is a well-known inducer of the innate immu... more The lipopolysaccharide (LPS) of Gram negative bacteria is a well-known inducer of the innate immune response. Toll-like receptor (TLR) 4 and myeloid differentiation factor 2 (MD-2) form a heterodimer that recognizes a common &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;pattern&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; in structurally diverse LPS molecules. To understand the ligand specificity and receptor activation mechanism of the TLR4-MD-2-LPS complex we determined its crystal structure. LPS binding induced the formation of an m-shaped receptor multimer composed of two copies of the TLR4-MD-2-LPS complex arranged symmetrically. LPS interacts with a large hydrophobic pocket in MD-2 and directly bridges the two components of the multimer. Five of the six lipid chains of LPS are buried deep inside the pocket and the remaining chain is exposed to the surface of MD-2, forming a hydrophobic interaction with the conserved phenylalanines of TLR4. The F126 loop of MD-2 undergoes localized structural change and supports this core hydrophobic interface by making hydrophilic interactions with TLR4. Comparison with the structures of tetra-acylated antagonists bound to MD-2 indicates that two other lipid chains in LPS displace the phosphorylated glucosamine backbone by approximately 5 A towards the solvent area. This structural shift allows phosphate groups of LPS to contribute to receptor multimerization by forming ionic interactions with a cluster of positively charged residues in TLR4 and MD-2. The TLR4-MD-2-LPS structure illustrates the remarkable versatility of the ligand recognition mechanisms employed by the TLR family, which is essential for defence against diverse microbial infection.