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Biomedical subjects

C Wu

Publications and source records attributed to C Wu.

At least 55 records · Page 3Linked to original sources

Preliminary evidence that estrogen protects against age-related hippocampal atrophy.

Few studies have examined gender differences in hippocampal volumes, and the potential effect of estrogen on these measures has not been well studied. We used MRI to measure hippocampal volumes in elderly Mexican American men and women subjects in order to determine if there were gender differences and if estrogen replacement therapy (ERT) had an effect on hippocampal volume in postmenopausal women. MRI measures of hippocampal volumes (normalized to intracranial volume) were compared in 59 women and 38 men. Further comparisons were made between men subjects, women subjects taking ERT, and women subjects not taking ERT. There were no significant effects of gender on normalized hippocampal volumes. However, women subjects taking ERT had larger right hippocampal volumes than women subjects not taking ERT and larger anterior hippocampal volumes than men subjects and women subjects not taking ERT. These findings suggest a neuroprotective effect of estrogen.

Aged↗

A description of Ca2+ channels in human detrusor smooth muscle.

OBJECTIVE: To characterize the Ca2+ channels in human detrusor smooth muscle and to investigate their contribution to spontaneous electrical activity. MATERIALS AND METHODS: Isolated human detrusor smooth muscle myocytes were used to measure ionic currents under voltage-clamp or membrane potential under current-clamp. Membrane potential oscillations were analysed in terms of oscillation frequency and amplitude using fast Fourier transforms. RESULTS: Under voltage-clamp an inward current dependent on extracellular Ca2+ was recorded using Cs+-filled patch electrodes. The current could be separated into two components on the basis of their sensitivity to Ni2+, verapamil or nicardipine, and their dependence on holding and clamp potential. A Ni2+-sensitive component activated over a relatively negative range of potentials (-60 to -20 mV) comprised about a third of the total current and was designated a T-type Ca2+ current. A verapamil/nicardipine-sensitive component, activated at more positive potentials, was designated an l-type Ca2+ current. Using K+-based filling solutions spontaneous transient outward currents were recorded that had the characteristics of current flow through BK channels. Membrane potential oscillations, under current-clamp increased in frequency but not amplitude as the mean membrane potential was made less negative. The voltage-dependence of oscillation frequency was similar to that of the l-type, but not T-type, Ca2+ current activation curve. Furthermore oscillation frequency was slowed by verapamil but not Ni2+. CONCLUSION: The study showed, for the first time, the presence of both T- and L-type Ca2+ channels in human detrusor smooth muscle; we propose a role for these channels in spontaneous activity. The results suggest that the L-type Ca2+ current can control membrane potential oscillation frequency. The significance of this finding for spontaneous contractions is discussed.

Calcium Channels, L-Type↗

In silico analysis indicates a similar gene expression pattern between human brain and testis.

OBJECTIVES: Previous data has reported similarity between human brain and testis gene expression patterns. Brain is the most important tissue in human speciation. Hence, it means that human testis could also play a crucial role in human speciation if these two tissues exhibit similar gene expression patterns. However, previous reports were based on only limited and scattered data. Determining the large scale anatomy of gene expression patterns of various human tissues could draw a more convincing conclusion, and better our understanding of the correlation/inter-correlation among different tissues. Furthermore, it could also provide a clue for evolutionary study. METHODS: To obtain gene expression information for large-scale data analysis, expression data of 760 Unigenes in seventeen human tissues (liver, lung, testis, brain, ovary, uterus, colon, stomach, heart, eye, kidney, spleen, gall bladder, breast, thymus, prostate and pancreas) were retrieved by DDD (differential digital display) analysis, and this expression data was subjected to clustering analysis. These Unigenes represent a wide range of genes classified according to their characterization and function. RESULTS: Among the 17 tissues, the highest similarity in gene expression patterns was between human brain and testis, based on DDD and clustering analysis. Genes contributing to the similarity include ribosomal protein (RP) genes as well as genes involved in transcription, translation and cell division. CONCLUSIONS: Present results provide evidence to support the proposal that human testis and brain share the highest similarity of gene expression patterns. The implications of the similarity regarding that both brain and testis contributed to human speciation are discussed.

Brain↗

Efficacy of pulsed-dye laser for viral warts--an internal audit.

Pulsed-dye laser (PDL) surgery is a recognized treatment of viral warts. Initial studies in 1993 by Tan et al achieved a 72% cure rate for 39 patients after a mean of 1.68 treatments. Since then, conflicting response rates ranging from 47-95% have been reported. The records of 44 patients, who attended the Laser Unit at St. James's Hospital between January 1999 to June 2000, were reviewed. Follow-up was conducted by telephone interview or questionnaire. Twenty-eight (64%) patients identified for the study responded. The average number of treatments was 4 (range 1-12) and mean treatment intervals were 4.9 weeks (3-10). Our results showed 64% complete clearance of all the areas treated, and 46% complete clearance of the 13 areas identified as recalcitrant. Rates for complete clearance varied with anatomic site: 73% for the face, 68% for the hands, and 40% for feet. Seventy-eight percent (7/9) of periungal warts completely cleared, and 70% (7/10) mosaic warts cleared. Twenty-five percent of the patients complained of severe pain during treatment. Post-operative complications were few, and rarely affected the patients' lifestyle. The recurrence of warts, in weeks to months following the last treatment, was reported by 36% of the patients. Seventy-nine percent of patients were satisfied with the treatment they were given. PDL may be useful in treatment of refractory warts in selected patient populations. The study identified a need to address pain control in a significant number of patients.

Adolescent↗

The role of the L-type Ca(2+) channel in refilling functional intracellular Ca(2+) stores in guinea-pig detrusor smooth muscle.

The transient rise of intracellular Ca(2+) in detrusor smooth muscle cells is due to the release of Ca(2+) from intracellular stores. However, it is not known how store refilling is maintained at a constant level to ensure constancy of the contractile response. The aim of these experiments was to characterise the role of L-type Ca(2+) channels in refilling. Experiments used isolated guinea-pig detrusor myocytes and store Ca(2+) content was estimated by measuring the magnitude of change to the intracellular [Ca(2+)] ([Ca(2+)](i)) after application of caffeine or carbachol using epifluorescence microscopy. Membrane potential was controlled when necessary by voltage clamp. After Ca(2+) stores were emptied they refilled with an exponential time course, with a time constant of 88 s. The value of the time constant was similar to that of the undershoot of [Ca(2+)](i) following store Ca(2+) release. The degree of store filling was enhanced by maintained depolarisation, or by transient depolarising pulses, and attenuated by L-type Ca(2+) channel antagonists. Inhibition of the sarcoplasmic reticular Ca(2+)-ATPase prevented refilling. Reduction of the resting [Ca(2+)](i) was accompanied by membrane depolarisation; under voltage clamp reduction of [Ca(2+)](i) decreased the number and magnitude of spontaneous transient outward currents. Ca(2+) release from intracellular stores, elicited by caffeine or carbachol, is independent of membrane potential under physiological conditions. However, store refilling occurs via Ca(2+) influx through L-type Ca(2+) channels. Ca(2+) influx is regulated by a feedback mechanism whereby a fall of [Ca(2+)](i) reduces the activity of Ca(2+)-activated K(+) channels, causing cell depolarisation and an enhancement of L-type Ca(2+) channel conductance.

Animals↗

Genomic-scale analysis of gene expression profiles in TNF-alpha treated human umbilical vein endothelial cells.

OBJECTIVE AND DESIGN: TNF-alpha is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, and in the control of cell proliferation, differentiation and programmed cell death. However, it is known that TNF-alpha is also the founding member of a still growing family of cytokines with diverse bioregulative functions. Its detailed molecular mechanisms on endothelial activation and injury remain to be elucidated. This study was aimed at determining genomic-scale gene expression profiles in TNF-alpha treated human endothelial cells. MATERIALS AND METHODS: In this study cultured human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha (10 ng/ml) for 2 and 16 h, respectively, and the gene expression pattern was profiled using a cDNA array representing 14,000 gene/cDNA clusters. RESULTS: In total, 72 known human genes were identified the expression levels of which altered over 2-fold in response to TNF-a stimulation. Such alteration was confirmed for IL-8 and MCP-1, with an independent quantitative mRNA assay. It was observed that genes with related biological functions were often temporally co-regulated. CONCLUSIONS: These results indicate the transcriptional pathways mediated by TNF-alpha inside the HUVECs. Expression profiling in HUVECs responding to TNF-alpha stimulation should give an understanding of the molecular mechanisms involved in vascular inflammation.

Cells, Cultured↗

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and their soluble receptors in coal workers' pneumoconiosis.

The aim of this study was to investigate whether systemic tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors (p55, p75), interleukin 6 (IL-6), and soluble IL-6 receptor could be markers of biological activities of coal workers' pneumoconiosis (CWP). The study population was composed of 182 Chinese retired coal miners who had similar dust exposure histories. Among them, 71 were cases with CWP and 111 were controls. Chest radiographs were classified according to International Labour Organization Criteria (ILO, 1980). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Serum concentrations of TNF-alpha, TNF-alpha receptors (p55, p75), IL-6, and IL-6 receptor were measured by ELISA techniques. Mean serum levels of p55, p75 and IL-6 were significantly higher in cases than in controls (P < or = 0.01 for each comparison by crude analyses). Results from logistic regression models, adjusted for age, dust exposure variables, and smoking habits, found similar associations between soluble p55 and p75 levels and the presence of CWP. Linear regression analysis revealed that CWP radiographic stage (by ILO criteria) was significantly correlated with the individual serum concentrations of p55, p75 and IL-6. Serum concentrations of all measured cytokines were notcorrelated to age, dust exposure, or smoking, but there were correlations between soluble p75 and p55 levels, and between p75 and IL-6 levels. The results of this study suggest that serum levels of TNF receptors and IL-6 are associated with the fibrotic process of CWP and serum cytokine levels may be correlated with the severity of CWP.

Aged↗

Genetic diversity of Chinese native chicken breeds based on protein polymorphism, randomly amplified polymorphic DNA, and microsatellite polymorphism.

Genetic diversity of Chinese native chicken breeds was investigated using protein polymorphism, randomly amplified polymorphic DNA (RAPD), and microsatellite polymorphism. Imported broiler and layer breeds were also included in the analysis. The results from protein polymorphism did not show distinct differences between Chinese native chicken and imported broilers; however, there were small significant differences between these two types of chickens. The results from RAPD indicated that gene diversity within a population was large in Chinese native chickens, intermediate in broilers, and low in layers and that there were small differences between Chinese native chickens and both broilers and layers. A great difference between broilers and layers was observed. Microsatellite polymorphism data showed that genetic diversity was high in the Chinese native chickens and low in layers and that there was a close relationship between Chinese native chickens and broiler but a remote relationship between Chinese native chickens and layers. The wide genetic diversity of Chinese native breeds can meet different requirements of breeding for chicken quality in China.

Alkaline Phosphatase↗

Comparative analysis of allozyme, random amplified polymorphic DNA, and microsatellite polymorphism on Chinese native chickens.

Allozyme, random amplified polymorphic DNA (RAPD), and microsatellite polymorphisms were examined and compared among five native populations of Chinese chickens, two fast-growing broiler lines, and one layer line. Three assay systems resulted in a different average heterozygosity or gene diversity in each of the eight populations. The lowest average heterozygosity was obtained with allozyme analysis (0.2209), intermediate heterozygosity was obtained with RAPD (0.2632), and the highest heterozygosity was observed with microsatellite analysis (0.7591). The genetic distances among all populations measured by three methods were also different. Allozyme data showed close relationships between Chinese native chickens and the two broiler lines, but they were both remotely related to the layer line. Microsatellite polymorphism analysis was similar to the allozyme analysis but genetic distances from RAPD showed a close relationship between Chinese native chickens and broiler and layer chickens.

Albumins↗

Sublethal cerebral ischemia inhibits caspase-3 activation induced by subsequent prolonged ischemia in the C57Black/Crj6 strain mouse.

Caspase-3 activation has been implicated in ischemic neuronal death. In the present study, we examined if cerebral ischemic tolerance induced by sublethal ischemia is associated with an attenuation of caspase-3 activation in a mouse forebrain ischemia model. Forebrain ischemia in C57Black/Crj6 strain mice was induced by bilateral common carotid artery occlusion (BCCAO) for 18 min. Two episodes of 6-min ischemia were carried out as preconditioning 48 and 72 h before the 18-min BCCAO. Caspase-3-like activity was determined by fluorescently monitoring the release of amino-4-methylcoumarin from N-acetyl-Asp-Glu-Val-Asp-7-amino-4-methylcoumarin in the striatal protein extracts at 4, 24, and 72 h after reperfusion. The results showed that the ischemic preconditioning significantly attenuated caspase-3 activation at 4, 24, and 72 h after reperfusion, and reduced neuronal loss caused by the 18-min ischemia as examined on the 7th day after reperfusion. The present results suggest that the neuroprotection achieved by ischemic preconditioning is related to an attenuation of caspase-3 activation.

Animals↗

Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF.

Nucleosome Remodeling Factor (NURF) is an ATP-dependent nucleosome remodeling complex that alters chromatin structure by catalyzing nucleosome sliding, thereby exposing DNA sequences previously associated with nucleosomes. We systematically studied how the unstructured N-terminal residues of core histones (the N-terminal histone tails) influence nucleosome sliding. We used bacterially expressed Drosophila histones to reconstitute hybrid nucleosomes lacking one or more histone N-terminal tails. Unexpectedly, we found that removal of the N-terminal tail of histone H2B promoted uncatalyzed nucleosome sliding during native gel electrophoresis. Uncatalyzed nucleosome mobility was enhanced by additional removal of other histone tails but was not affected by hyperacetylation of core histones by p300. In addition, we found that the N-terminal tail of the histone H4 is specifically required for ATP-dependent catalysis of nucleosome sliding by NURF. Alanine scanning mutagenesis demonstrated that H4 residues 16-KRHR-19 are critical for the induction of nucleosome mobility, revealing a histone tail motif that regulates NURF activity. An exchange of histone tails between H4 and H3 impaired NURF-induced sliding of the mutant nucleosome, indicating that the location of the KRHR motif in relation to global nucleosome structure is functionally important. Our results provide functions for the N-terminal histone tails in regulating the mobility of nucleosomes.

Adenosine Triphosphate↗

Influence of ibuprofen as a solid-state plasticizer in Eudragit RS 30 D on the physicochemical properties of coated beads.

The purpose of this study was to investigate the physicochemical properties of nonpareil beads coated with Eudragit RS 30 D containing ibuprofen as a multifunctional agent. The influence of the concentration of ibuprofen in the film coating and the effect of the coating level on drug release from coated beads was determined in pH 7.2 phosphate buffer solution. The influence of storage time at 23 degrees C and 60 degrees C on the release of ibuprofen from coated beads was also investigated. The thermal properties of the films were determined using a differential scanning calorimeter. Scanning electron microscopy was employed to image the surface morphology of the coated beads. Infrared spectroscopy was used to study the interaction of Eudragit RS 30 D and ibuprofen. Results from the dissolution studies demonstrated that increasing the amount of ibuprofen in the polymeric film reduced the rate of drug release, mainly because of a more complete coalescence of the polymeric particles of the latex dispersion. The glass transition temperature (Tg) of Eudragit RS 30 D films decreased and the surface of the coated beads became smoother as the concentration of ibuprofen was increased. Hydrogen bonding between the polymer and ibuprofen was demonstrated by Fourier transform infrared spectroscopy. No significant differences were found in drug dissolution between the coated beads stored at 23 degrees C for 12 months and those stored at 60 degrees C for 12 hours. The results of this study demonstrated that the ibuprofen plasticized the Eudragit RS 30 D. Furthermore, the dissolution rate of ibuprofen can be controlled and changes in the drug release rate can be minimized by using the drug-induced plasticization technique with this polymer.

Acrylic Resins↗

Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes.

How intracellular cytoskeletal and signaling proteins connect and communicate with the extracellular matrix (ECM) is a fundamental question in cell biology. Recent biochemical, cell biological, and genetic studies have revealed important roles of cytoplasmic integrin-linked kinase (ILK) and its interactive proteins in these processes. Cell adhesion to ECM is an important process that controls cell shape change, migration, proliferation, survival, and differentiation. Upon adhesion to ECM, integrins and a selective group of cytoskeletal and signaling proteins are recruited to cell matrix contact sites where they link the actin cytoskeleton to the ECM and mediate signal transduction between the intracellular and extracellular compartments. In this review, we discuss the molecular activities and cellular functions of ILK, a protein that is emerging as a key component of the cell-ECM adhesion structures.

Actin Cytoskeleton↗

Application of the polysilicone fullerene coating for solid-phase microextraction in the determination of semi-volatile compounds.

Solid-phase microextraction using polysilicone fullerene (PF) coating has been applied for the determination of semi-volatile compounds. Detection limits at the 10 ng l(-1) to approximately microg l(-1) level were achieved using flame ionization detection. A wide linear range was obtained with precision below 7% relative standard deviation. Parameters that affect the extraction process were investigated, which included sampling time, desorption time, sampling temperature, and salting out effect. Compared to the non-polar commercial polydimethylsiloxane (PDMS) coating, the PF coating has higher extraction efficiency, better selectivity and greater sensitivity for aromatic compounds. The experimental results revealed the thermal stability and life span are superior to commercially available PDMS. The PF coating has been demonstrated to possess planarity molecular recognition. The theoretical study confirmed that quantification is feasible under non-equilibrium conditions by use of the PF coating.

Reproducibility of Results↗

RyR3 amplifies RyR1-mediated Ca(2+)-induced Ca(2+) release in neonatal mammalian skeletal muscle.

The neonatal mammalian skeletal muscle contains both type 1 and type 3 ryanodine receptors (RyR1 and RyR3) located in the sarcoplasmic reticulum membrane. An allosteric interaction between RyR1 and dihydropyridine receptors located in the plasma membrane mediates voltage-induced Ca(2+) release (VICR) from the sarcoplasmic reticulum. RyR3, which disappears in adult muscle, is not involved in VICR, and the role of the transiently expressed RyR3 remains elusive. Here we demonstrate that RyR1 participates in both VICR and Ca(2+)-induced Ca(2+) release (CICR) and that RyR3 amplifies RyR1-mediated CICR in neonatal skeletal muscle. Confocal measurements of intracellular Ca(2+) in primary cultured mouse skeletal myotubes reveal active sites of Ca(2+) release caused by peripheral coupling between dihydropyridine receptors and RyR1. In myotubes lacking RyR3, the peripheral VICR component is unaffected, and RyR1s alone are able to support inward CICR propagation in most cells at an average speed of approximately 190 microm/s. With the co-presence of RyR1 and RyR3 in wild-type cells, unmitigated radial CICR propagates at 2,440 microm/s. Because neonatal skeletal muscle lacks a well developed transverse tubule system, the RyR3 reinforcement of CICR seems to ensure a robust, uniform, and synchronous activation of Ca(2+) release throughout the cell body. Such functional interplay between RyR1 and RyR3 can serve important roles in Ca(2+) signaling of cell differentiation and muscle contraction.

Animals↗

Nerve growth factor activates persistent Rap1 signaling in endosomes.

We investigated a role for endogenous Rap1, a small monomeric GTP-binding protein of the Ras family, in nerve growth factor (NGF) signaling in PC12 cells. Although both epidermal growth factor (EGF) and NGF caused transient activation of Ras, only NGF induced the activation of Rap1. Moreover, Rap1 activation was sustained for hours, an effect that matched the sustained activation of the mitogen-activated protein kinase (MAPK) pathway. To investigate the molecular basis for Rap1 activation, we examined complexes containing C3G, a guanine nucleotide exchange factor for Rap1, and CrkL, an adapter protein known to influence Rap1 signaling. NGF induced the formation of a long-lived complex containing C3G/CrkL/Shp2/Gab2/TrkA. Linking the complex to Rap1 activation, we coprecipitated activated TrkA and activated MAPK with activated Rap1 in NGF-treated cells. Confocal microscopy and subcellular fractionation showed that activated Rap1 and the other proteins of the signaling complex were present in endosomes. Pretreatment of PC12 cells with brefeldin A (BFA), which disrupts the Golgi and endosomal compartments, had little effect on Ras activation but strongly inhibited NGF-induced Rap1 activation and continuing MAPK activation. We propose that endosomes are a site from which NGF induces the prolonged activation of Rap1 and MAPK.

Adaptor Proteins, Signal Transducing↗