Biomedical subjects

Y-L Chen

Publications and source records attributed to Y-L Chen.

18 recordsLinked to original sources

PubMed2006

hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells.

Telomerase activity is suppressed in normal somatic tissues but is activated in most cancer cells. We have previously found that all six telomerase subunit proteins, including hTERT and hsp90 are needed for full enzyme activity. Telomerase activity has been reported to be upregulated by protein kinase C (PKC), but the mechanism is not clear. In this study, we examined how PKC regulates telomerase activity in head and neck cancer cells. PKC inhibitor, bisindolylmaleimide I (BIS), inhibited telomerase activity but had no effect on the expressions of telomerase core subunits. RNA interference (RNAi) and in vitro phosphorylation studies revealed that PKC isoforms alpha, beta, delta, epsilon, zeta specifically involved in telomerase regulation, and the phosphorylation target was on hTERT. Treatment with the hsp-90 inhibitor novobiocin dissociated hsp90 and hTERT as revealed by immunoprecipitation and immunoblot analysis and reduced telomerase activity. Treatment with the PKC activator SC-10 restored the association of hsp90 and hTERT and reactivate telomerase, suggesting that hTERT phosphorylation by PKC is essential for telomerase holoenzyme integrity and function. Analysis on clinical normal and tumour tissues reveal that the expressions of PKC alpha, beta, delta, epsilon, zeta were higher in the tumour tissues, correlated with telomerase activity. Disruption of PKC phosphorylation by BIS significantly increased chemosensitivity to cisplatin. In conclusion, PKC isoenzymes alpha, beta, delta, epsilon, zeta regulate telomerase activity in head and neck cancer cells by phosphorylating hTERT. This phosphorylation is essential for telomerase holoenzyme assembly, leading to telomerase activation and oncogenesis. Manipulation of telomerase activity by PKC inhibitors is worth exploring as an adjuvant therapeutic approach.

Cell Transformation, Neoplastic↗

PubMed2006

Influence of diabetes mellitus on deep neck infection.

OBJECTIVE: To investigate the influence of hyperglycaemia on deep neck infection (DNI) and the differences between the diabetic and non-diabetic form of DNI. STUDY DESIGN AND SETTING: Retrospective review of 131 patients with DNI treated between 1993 and 2002 at Shin Kong Memorial Hospital, Taipei, Taiwan. RESULTS: Deep neck infection was significantly more prevalent in patients with diabetes mellitus (DM) over 60 years of age than in non-DM subjects of a similar age (p = 0.004). In the DM group, Klebsiella pneumoniae was the most common aerobic pathogen and tended to involve more than two anatomical spaces (p < 0.0001). Seventeen out of 18 patients (94.4 per cent) displayed an elevated (> or = 7 per cent) glycosylated haemoglobin level. The DM group had a significantly higher complication rate, longer hospital stay and tracheotomy rate than the non-DM group. CONCLUSIONS: Diabetic DNI differs from non-diabetic DNI in several aspects and is associated with a higher morbidity. A greater than normal haemoglobin A1c level was commonly observed.

Adolescent↗

PubMed2006

Identification of the osteoprotegerin/receptor activator of nuclear factor-kappa B ligand system in gingival crevicular fluid and tissue of patients with chronic periodontitis.

BACKGROUND AND OBJECTIVE: Recent findings have suggested that osteoclastogenesis is directly regulated by receptor activator of nuclear factor-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). However, no studies have described interactions of OPG/RANKL and the gp130 cytokine family in periodontal disease. This study aimed to identify and quantify OPG/RANKL in the gingival crevicular fluid (GCF) and connective tissue of patients with periodontitis, and to clarify possible correlations with disease severity and interleukin-6 (IL-6) cytokines. MATERIAL AND METHODS: Ninety-five sites in 20 patients with generalized chronic periodontitis were divided into four groups by site based on probing depth (PD) and bleeding on probing (BOP). In periodontitis patients, GCF was obtained using sterile paper strips from clinically healthy sites (PD 6 mm with BOP, n = 27). Fourteen clinically healthy sites from four periodontally healthy individuals were used as the control group. The levels of OPG, RANKL and two gp130 cytokines - IL-6 and oncostatin M (OSM) - in the GCF were determined by an enzyme-linked immunosorbent assay (ELISA) and are expressed as total amounts (pg/site). Immunohistochemical localization of OPG- and RANKL-positive cells was also performed on gingival connective tissues harvested from patients with periodontitis (inflammatory group, n = 8 biopsies) and from non-diseased individuals (healthy group, n = 8 biopsies). RESULTS: GCF RANKL, but not OPG, was elevated in diseased sites of patients with periodontitis. However, the expressions of OPG and RANKL showed no correlation with disease severity (r = 0.174 and 0.056, respectively), but the content of RANKL in the GCF was significantly positively correlated with those of IL-6 (r = 0.207) and OSM (r = 0.231) (p < 0.01). Immunohistochemical staining showed that RANKL-positive cells were significantly distributed in the inflammatory connective tissue zone of diseased gingiva, compared with those of samples from non-diseased persons (p < 0.01). However, few OPG-positive cells were found in connective tissue zones of either the diseased gingiva or healthy biopsies. CONCLUSION: These findings imply that in this cross-sectional study of GCF, RANKL, IL-6 and OSM were all prominent in periodontitis sites, whereas OPG was inconsistently found in a few samples of diseased sites but was undetectable in any of the control sites. The results also imply that the expression of RANKL was positively correlated with IL-6 and OSM in the GCF.

Adult↗

PubMed2005

Potential of mean force between two nanometer-scale particles in a polymer solution.

Expanded ensemble density-of-states simulations and a connectivity altering algorithm are used to investigate the effective interactions that arise between nanoparticles suspended in polymer solutions. Our calculations with systems of long polymeric chains reveal oscillations in the effective polymer-induced interactions between the particles, even at low concentrations. The range of these interactions is considerably longer than originally anticipated, and their origin is traced back to the chain-end effects and density fluctuations that were absent in previous treatments of these systems.

Journal Article↗

PubMed2005

Barrier hopping, viscous flow, and kinetic gelation in particle-polymer suspensions.

The naive mode coupling-polymer reference interaction site model (MCT-PRISM) theory of gelation and elasticity of suspensions of hard sphere colloids or nanoparticles mixed with nonadsorbing polymers has been extended to treat the emergence of barriers, activated transport, and viscous flow. The barrier makes the dominant contribution to the single particle relaxation time and shear viscosity, and is a rich function of the depletion attraction strength via the polymer concentration, polymer-particle size asymmetry ratio, and particle volume fraction. The dependences of the barrier on these three system parameters can be accurately collapsed onto a single scaling variable, and the resultant master curve is well described by a power law. Nearly universal master curves are also constructed for the hopping or alpha relaxation time for system conditions not too close to the ideal MCT transition. Based on the calculated barrier hopping time, a theory for kinetic gel boundaries is proposed. The form and dependence on system parameters of the kinetic gel lines are qualitatively the same as obtained from prior ideal MCT-PRISM studies. The possible relevance of our results to the phenomenon of gravity-driven gel collapse is studied. The general approach can be extended to treat nonlinear viscoelasticity and rheology of polymer-colloid suspensions and gels.

Journal Article↗

PubMed2005

Effects of surface electrical stimulation on the muscle-tendon junction of spastic gastrocnemius in stroke patients.

PURPOSE: The purpose of this study was to explore the effects of spasticity suppression by surface electrical stimulation (ES) o the muscle-tendon junction of spastic gastrocnemius muscles in stroke. METHODS: Twenty-four neurologically stable stroke patients (aged 41-69 years, 12-35 months post-stroke), with spasticity graded 2 or 3 on the modified Ashworth scale, were recruited and divided into two groups. In the ES group, each patient received 20 min of surface ES once daily, 6 days per week for 1 month. In the control groups, ES was used with stimulation intensity kept at zero. To evaluate the therapeutic effect, the modified Ashworth scale, Fmax/Mmax ratio, H-reflex latency, H-reflex recovery curve, and the 10-m walking time were tested before and after the 1-month of treatment. RESULTS: In the ES group, the modified Ashworth scale showed a trend toward reduced spasticity after 1 month of treatment. The Fmax/Mmax ratio decreased from 8.10% +/- 4.84% to 4.00% +/- 1.36%; the H-reflex latency increased from 28.87 +/- 2.45 ms to 29.40 +/- 2.57 ms; the H-reflex recovery curves indicated a downward shift; and the 10-metre walking time significantly decreased after ES. In the control group, none of the measures showed a statistically significant change. CONCLUSIONS: In this study, we demonstrated a way to suppress spasticity at a metameric site and to increase walking speed effectively by applying surface ES on the muscle-tendon junction of spastic gastrocnemius muscles.

Adult↗

PubMed2005

Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice.

BACKGROUND: Surfactant protein D (SP-D) is involved in the innate immunity within the lung and may have important roles in modulating the inflammatory process of asthma. OBJECTIVE: To examine the potential immunomodulating role of SP-D on the allergic response in mice, and its interaction with the alveolar macrophages (AMs) during allergic inflammation. METHODS: A recombinant 60 kDa fragment of human SP-D (rfh SP-D), Survanta, and budesonide were administrated, respectively, to Der p-sensitive BALB/c mice before or after allergen challenge (AC). Total and differential cell counts, levels of cytokines in bronchoalveolar lavage fluids(BALFs), and levels of Der p-specific IgE and IgG1 antibodies in sera, were assayed. The production of nitric oxide (NO), and inducible NO synthase (iNOS) expression, in AMs, were determined by ELISA and RT-PCR, respectively. RESULTS: Instillation of rfh SP-D to sensitized mice 6 h after AC (therapeutic), but not 24 h before AC (preventive), markedly reduced infiltration of eosinophils, and also reduced levels of IL-4, IL-5, eotaxin, and TNF-alpha but elevated levels of IFN-gamma in the BALF. These effects were comparable with those obtained with budesonide treatment, whereas Survanta did not have a suppressive effect, either before or after AC. There was significant inhibition of NO production in the rfh SP-D pre-treated AMs of allergen-sensitized mice, but not in naive mice. CONCLUSIONS: These results indicate that rfh SP-D has a therapeutic effect on allergen-induced bronchial inflammation, and that this might be because of its inhibitory effect on NO and TNF-alpha production by AMs, and it thus prevents the development of T-helper type 2 cytokine response.

Allergens↗

PubMed2005

ABO/secretor genetic complex is associated with the susceptibility of childhood asthma in Taiwan.

BACKGROUND: Histo-blood groups, ABO, Lewis (Le) and secretor (Se) were found to be associated with lower lung function and wheezing in coal miners as well as in asthmatic children in some studies but not others, possibly reflecting the genetic heterogeneity among different ethnicities and local environmental exposure. OBJECTIVE: The present study was conducted to determine the association between ABO, Lewis and secretor genetic complex with susceptibility of childhood asthma in Taiwan. METHODS: We randomly selected 136 asthmatic children and 161 age-matched controls from a childhood asthma survey conducted in primary schools. ABO and Lewis blood groups were determined by red blood cell agglutination methods. Analysis of Se genotype was performed by PCR with sequence-specific primers. RESULTS: There was a higher prevalence rate in secretor subjects (Se/Se) (odds ratio (OR)=1.7, confidence interval (CI)=1.022-2.938) in asthma as compared with controls. The combined effect of these three blood systems revealed that blood group O/secretor phenotype (Se/Se) (OR=2.7, CI=1.126-6.033), and blood group O/Le(a-b-) (OR=3.6, CI=1.080-11.963, P<0.03) individuals were significantly associated with asthma. The Lewis Le(a-b-) recessive genotype (OR=3.3, CI=1.267-8.482), or the joint blood group O/Le(a-b-) phenotype (OR=5.2, CI=1.259-21.429, P<0.02), was significantly associated with high serum IgE (>500 IU), respectively. There was no association of these three blood systems with the sensitivity of dust mite, Dermatophagoide pteronyssinus, in our study population. CONCLUSIONS: We concluded that blood group O/secretors (Se/Se) and O/Le(a-b-) were associated with childhood asthma, and may act as one of the predominant factors for environmental triggers of allergy for asthmatic children in Taiwan.

ABO Blood-Group System↗

PubMed2005

Mite allergen induces nitric oxide production in alveolar macrophage cell lines via CD14/toll-like receptor 4, and is inhibited by surfactant protein D.

BACKGROUND: Previously, we have found that dust mite allergens can directly activate alveolar macrophages (AMs), induce inflammatory cytokines, and enhance T-helper type 2 cytokine production. A molecule of innate immunity in the lung, surfactant protein D (SP-D), is able to bind mite allergens and alleviates allergen-induced airway inflammation. OBJECTIVES: This study was aimed at investigating the activation pathway of mite allergen (Dermatophagoides pteronyassinus, Der p)-induced nitric oxide (NO) production by AMs, and the role of SP-D in the modulation of activated AMs by mite allergens. METHODS: Porcine SP-D was purified from bronchoalveolar lavage fluids of Lan-Yu mini-pigs, by affinity chromatography on maltose-sepharose. NO production, inducible expression of lipopolysaccharides (LPS)-related binding and responding surface receptors complex, CD14 and toll-like receptor 4 (TLR4), as well as inducible NO synthase (iNOs) and nuclear factor-kappaB activation were studied in two AMs cell lines, MH-S (BALB/c strain),and AMJ2-C11 (C57BL/6 strain), and one peritoneal macrophage cell line (RAW264.7), after stimulation with LPS, or Der p. RESULTS: LPS and Der p elicited different responses of NO production in the different cell lines, and the response might depend upon the expression of the cell surface CD14/TLR4 complex in different genetic backgrounds of macrophage cell lines. Pretreatment of macrophages with SP-D could inhibit NO production from Der p or LPS-stimulated alveolar macrophages. CONCLUSION: Mite allergen-induced alveolar macrophage activation is mediated by CD14/TLR4 receptors and can be inhibited by SP-D; it further supports the concept that SP-D may be an important modulator of allergen-induced pulmonary inflammation.

Animals↗

PubMed2005

Inhibition of angiotensin II induced endothelin-1 gene expression by 17-beta-oestradiol in rat cardiac fibroblasts.

OBJECTIVE: To examine whether 17-beta-oestradiol (E(2)) may alter angiotensin II (Ang II) induced cell proliferation and to identify the putative underlying signalling pathways in rat cardiac fibroblasts. DESIGN: Cultured rat cardiac fibroblasts were preincubated with E(2) then stimulated with Ang II. [(3)H]Thymidine incorporation and endothelin-1 (ET-1) gene expression were examined. The effect of E(2) on Ang II induced NADPH oxidase activity, reactive oxygen species (ROS) formation, and extracellular signal regulated kinase (ERK) phosphorylation were tested to elucidate the intracellular mechanism of E(2) in proliferation and ET-1 gene expression. RESULTS: Ang II increased DNA synthesis, which was inhibited with E(2) (1-100 nmol/l). E(2), but not 17-alpha-oestradiol, inhibited Ang II induced ET-1 gene expression as shown by northern blotting and promoter activity assay. This effect was prevented by co-incubation with the oestrogen receptor antagonist ICI 182,780 (1 micromol/l). E(2) also inhibited Ang II increased NADPH oxidase activity, ROS formation, ERK phosphorylation, and activator protein-1 mediated reporter activity. CONCLUSIONS: The results suggest that E(2) inhibits Ang II induced cell proliferation and ET-1 gene expression, partially by interfering with the ERK pathway through attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of oestrogen on the cardiovascular system.

Angiotensin II↗

PubMed2004

Conformation and dynamics of single DNA molecules in parallel-plate slit microchannels.

The conformation and diffusion of a single DNA molecule confined between two parallel plates are examined using both single molecule experiments and Brownian dynamics simulations accounting for hydrodynamic interactions. The degree of chain stretching and the diffusivity are characterized as a function of the chain confinement and the channel geometry. Good agreement is found between the simulations, experiments, and scaling theory predictions.

Computer Simulation↗

PubMed2004

Elasticity and clustering in concentrated depletion gels.

X-ray scattering and rheology are employed to study the volume fraction dependence of the collective structure and elastic moduli of concentrated nanoparticle-polymer depletion gels. The nonequilibrium gel structure consists of locally densified nonfractal clusters and narrow random interfaces. The elastic moduli display a power law dependence on volume fraction with effective exponents that decrease with increasing depletion attraction strength. A microscopic theory that combines local structural information with a dynamic treatment of gelation is in good agreement with the observations.

Colloids↗

PubMed2004

Polymer-particle mixtures: depletion and packing effects.

The structure of polymers in the vicinity of spherical colloids is investigated by Monte Carlo simulations and integral equation theory. Polymers are represented by a simple bead-spring model; only repulsive Lennard-Jones interactions are taken into account. Using advanced trial moves that alter chain connectivity, depletion and packing effects are analyzed as a function of chain length and density, both at the bond and the chain level. Chain ends segregate to the colloidal surface and polymer bonds orient parallel to it. In the dilute regime, the polymer chain length governs the range of depletion and has a negligible influence on monomer packing in dense polymer melts. Polymers adopt an ellipsoidal shape, with the larger axis parallel to the surface of the particle, as they approach larger colloids. The dimensions are perturbed within the range of the depletion layer.

Journal Article↗

PubMed2004

Adenovirus-mediated overexpression of catalase attenuates oxLDL-induced apoptosis in human aortic endothelial cells via AP-1 and C-Jun N-terminal kinase/extracellular signal-regulated kinase mitogen-activated protein kinase pathways.

In a variety of vascular disorders, endothelial cells (ECs) are exposed to high levels of reactive oxygen species (ROS) generated intercellularly. Recently, several anti-oxidants, including catalase, have been suggested to be cytoprotective against the development of atherosclerosis. The object of this study was to investigate whether adenovirus-mediated gene transfer of catalase in ECs can attenuate ROS production and cell apoptosis under oxidized low density lipoprotein (oxLDL) stimulation. Adenovirus-mediated gene transfer of human catalase gene (Ad-Cat) resulted in a high level of catalase overexpression in human arterial EC (HAEC), which manifested a time-dependent increase in cell viability under the exposure of oxLDL and decreased oxLDL-induced apoptosis. Phosphorylation studies of ERK1/2, JNK, and p38, three subgroups of mitogen activator protein kinase demonstrated that catalase overexpression suppressed JNK phosphorylation and increased ERK1/2 phosphorylation. NF-kappaB and AP-1 were induced after the exposure of HAECs to oxLDL. While catalase overexpression was found to inactivate AP-1, it had no effect on NF-kappaB activity. These results provide the evidence that overexpression of catalase in ECs attenuates ROS production and cell apoptosis under oxLDL stimulation. The protective effect is mediated through the downregulation of JNK and the upregulation of ERK1/2 phosphorylation as well as AP-1 inactivation. This observation supports the feasibility of catalase gene transfer to human endothelium to protect against oxidant injury.

Adenoviridae↗

PubMed2003

A head orientated wheelchair for people with disabilities.

PURPOSE: Most electric wheelchairs available on the market are joystick-controlled making people with hand or arm disabilities unable to control the wheelchairs easily. This study proposes a new head-orientated wheelchair design for people with disabilities. METHOD: This study involves a tilt sensor module fitted onto the operator's headgear that will sense head movements used to control the wheelchair's direction and speed. This system includes: the tilt sensor module, the signal processing circuit and a main controller. RESULTS: The average times required for completing experiments by seven volunteers using joystick-controlled and the newly developed wheelchairs were recorded. It was revealed that the difference in average operating time for the two wheelchairs were statistically insignificant (p>0.05). CONCLUSIONS: The wheelchair developed in this study, although not absolutely superior to the joystick-controlled method, should still provide a better alternative for people with disabilities unsuited to traditional input devices.

Adult↗

PubMed2002

Granulocytes mediates the Fas-L-associated apoptosis during lung metastasis of melanoma that determines the metastatic behaviour.

The survival of tumour cells in a new tissue environment is crucial for tumour metastasis. Factors contributing to the death of tumour cells during metastasis are not completely understood. In murine melanoma model, activation of Fas (CD95, APO-1) signal in tumour cells reduces their lung metastasis potential, which may be associated with an induction of apoptosis in tumours. To elucidate the cellular mechanism, we used a Fas-ligand (Fas-L) specific ribozyme (Fas-L(ribozyme)) to suppress the expression of Fas-L but not Fas or TNF-alpha in B16F10 melanoma cells. The Fas-L(ribozyme)-carrying cells grew slightly faster in vitro with better viability than controls. Suppression of Fas-L in B16F10 melanoma cells by Fas-L(ribozyme) enhanced lung metastasis of the cells in C57BL/6 mice, and that was correlated with reductions in both apoptotic tumour cells and granulocytic infiltration. Mice depleted of granulocytes, but not CD4+ and CD8+ cells, showed a greatly elevated susceptibility to lung metastasis. Moreover, apoptosis in tumour cells was significantly reduced in granulocyte-depleted mice during the course of tumour formation. Taken together, our findings indicate that Fas-L-associated apoptosis in tumour cells determines the metastasis behaviour of melanoma in the lung and this apoptosis is primarily mediated by the cytotoxicity of recruited granulocytes.

Apoptosis↗

PubMed1997

A non-invasive protocol for the determination of lumbosacral vertebral angle.

OBJECTIVE: The purpose of this study was to develop a non-invasive method to predict the lumbosacral and vertebral angles. DESIGN: The candidate predicting variables were the externally measured marker angle, pelvic angle, and lumbosacral angle. BACKGROUND: Several investigators used surface rigid markers to represent the angles of lumbosacral vertebrae. Previous studies show a high level of validity for measuring the lumbar curvature during stance and for obtaining the vertebral angle in the lumbar region. However, our review of literature failed to find a data transformation model illustrating the lumbosacral vertebral angle using external measurements as predictors. METHODS: Sixteen healthy male subjects participated in the radiographic and videographic measurements. Data of 12 of the 16 subjects were used for model development, and data of the other four subjects were used for model validation. RESULTS: The results showed significant differences between the directly measured vertebral angle from the X-ray film and the externally measured angles of the surface markers at the L(5) and S(1) levels (P<0.05). Linear regression models for calculating vertebral angles were developed with R(2) values of 0.97, 0.98, 0.91, and 0.92 for the vertebral levels of L(1), L(3), L(5), and S(1) respectively. The validation result showed that there was no significant difference between the calculated and the X-ray data. CONCLUSIONS: The protocol of using the skin-surface rigid markers and the predicting models was justified in the study to provide a simple and valid non-invasive method for the recording of the internal vertebral angle in the sagittal plane. RELEVANCE: Measurements of lumbosacral vertebral angle are important in assessing the stresses acting on the low back in lifting. The results of this study provided a simple and valid non-invasive method by rigid markers for the prediction of internal vertebral angles under various trunk positions.

Journal Article↗

PubMedDate not supplied

Application of SEMG in computer mouse access for the disabilities.

PURPOSE: To improve the operating speed of the traditional row-column scanning computer keyboard-mouse composite panel controlled using a single key. METHOD: Using a single mouse input control window can avoid scanning unnecessary keyboard characters, thereby increasing the speed in performing mouse commands. In addition, the surface electromyographic (SEMG) sensing input can also be used to provide an input option for the disabled. RESULTS: Eleven volunteers operated the single mouse input control window using the SEMG input and the traditional computer keyboard-mouse composite panel controlled using a single key. The average operating times were 121.3+/-8.9 sec and 208.6+/-10.7 sec, respectively. The difference was statistically significant (p<0.05). CONCLUSIONS: The row-column scanning method with the single mouse control window using SEMG input can effectively decrease the operating time. Through this system, the disabled can operate a computer and lead an independent life.

Adult↗