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Biomedical subjects

X Wu

Publications and source records attributed to X Wu.

At least 55 records · Page 3Linked to original sources
PubMed2005

Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation.

Neural stem cells (NSCs) are present not only in the developing nervous systems, but also in the adult human central nervous system (CNS). It is long thought that the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus are the main sources of human adult NSCs, which are considered to be a reservoir of new neural cells. Recently adult NSCs with potential neural capacity have been isolated from white matter and inferior prefrontal subcortex in the human brain. Rapid advances in the stem cell biology have raised appealing possibilities of replacing damaged or lost neural cells by transplantation of in vitro-expanded stem cells and/or their neuronal progeny. However, sources of stem cells, large scale expansion, control of the differentiations, and tracking in vivo represent formidable challenges. In this paper we review the characteristics of the adult human NSCs, their potentiality in terms of proliferation and differentiation capabilities, as well as their large scale expansion for clinical needs. This review focuses on the major advances in brain stem cell-based therapy from the clinical perspective, and summarizes our work in clinical phase I-II trials with autologuous transplantation of adult NSCs for patients with open brain trauma. It also describes multiple approaches to monitor adult human NSCs labeled superparamagnetic nanoparticles after transplantation and explores the intriguing possibility of stem cell transplantation.

Animals↗
PubMed2004

Time-frequency and coherence analysis of fMEG signals.

Fetal magnetoencephalographic (fMEG) measurements are performed with interference from the fetal and maternal magnetocardiogram (MCG). Fetal movement, fetal breathing, fetal eye blinks or eye rollings and maternal muscle-contraction may generate detectable signals. These factors can be called "interventions," which can be manifested in space and/or time. They make the fMEG signals nonstationary. By examining temporal relationship of the multi-channel records, we are able to find the spatial signature of these "interventions." The aim of this study is to examine nonstationarity in single channel and nonhomogeniety in multiple channels of the fMEG data. Preliminary results are reported here, and may be used in further studies, leading toward intervention identification, and ultimately fetal state determination.

Fetal Monitoring↗
PubMed2004

The accuracy of dynamic wedge dose computation in the ADAC Pinnacle RTP system.

The nonphysical wedge is a modality that uses computer-controlled jaw motion to generate wedge-shaped dose distributions. There are Varian enhanced dynamic wedges (EDWs) and Siemens virtual wedges (VWs). We recently commissioned dynamic wedges on both Varian and Siemens LINACs. The beam data, acquired with a Wellhofer chamber array and a Sun Nuclear profiler, are used for modeling in the ADAC Pinnacle system. As recommended by ADAC, only a limited number of beam data is measured and used for beam modeling. Therefore, the dose distributions of dynamic wedges generated by Pinnacle must be examined. Following the commissioning of the dynamic wedges, we used Pinnacle to generate a number of dose distributions with different energies, wedge angles, field sizes, and depths. The computed data from Pinnacle are then compared with the measured data. The deviations of the output factor in all square and rectangular fields are mostly within 2.0% for both EDW and VW. For asymmetric fields, the deviations are within 3%. However, exceptions of differences more than 3% have been found in a larger field and large wedge combinations. The precision of the beam profiles generated by Pinnacle is also evaluated. As a result of this investigation, we present a scope of quality assurance tests that are necessary to ensure acceptable consistency between the delivered dose and the associated treatment plan when dynamic wedges are applied.

Equipment Failure Analysis↗
PubMed2004

Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase.

The contributing role of environmental factors to the development of Parkinson's disease has become increasingly evident. We report that mesencephalic neuron-glia cultures treated with diesel exhaust particles (DEP; 0.22 microM) (5-50 microg/ml) resulted in a dose-dependent decrease in dopaminergic (DA) neurons, as determined by DA-uptake assay and tyrosine-hydroxylase immunocytochemistry (ICC). The selective toxicity of DEP for DA neurons was demonstrated by the lack of DEP effect on both GABA uptake and Neu-N immunoreactive cell number. The critical role of microglia was demonstrated by the failure of neuron-enriched cultures to exhibit DEP-induced DA neurotoxicity, where DEP-induced DA neuron death was reinstated with the addition of microglia to neuron-enriched cultures. OX-42 ICC staining of DEP treated neuron-glia cultures revealed changes in microglia morphology indicative of activation. Intracellular reactive oxygen species and superoxide were produced from enriched-microglia cultures in response to DEP. Neuron-glia cultures from NADPH oxidase deficient (PHOX-/-) mice were insensitive to DEP neurotoxicity when compared with control mice (PHOX+/+). Cytochalasin D inhibited DEP-induced superoxide production in enriched-microglia cultures, implying that DEP must be phagocytized by microglia to produce superoxide. Together, these in vitro data indicate that DEP selectively damages DA neurons through the phagocytic activation of microglial NADPH oxidase and consequent oxidative insult.

Animals↗
PubMed2004

Integration target site selection for retroviruses and transposable elements.

When a retrovirus infects a cell, its RNA genome is reverse transcribed into a double-stranded DNA, which is then permanently integrated into the host chromosome. Integration is one of the essential steps in the retroviral life cycle. Many transposable elements also move around and integrate into the host genome as part of their life cycle, some through RNA intermediates and some through 'cut and paste' mechanisms. Integration of retroviruses and transposable elements into 'sensitive areas' of the genome can cause irreparable damage. On the other hand, because of their ability to integrate permanently, and the relatively efficient rates of transgenesis, retroviruses and transposable elements are widely used as gene delivery tools in basic research and gene therapy trials. Recent events in gene therapy treatments for X-linked severe combined immunity deficiencies (X-SCID) have highlighted both the promise and some of the risks involved with utilizing retroviruses. Nine of 11 children were successfully treated for X-SCID using a retrovirus carrying the gene mutated in this disease. However, later two of these children developed leukemias because of retroviral integrations in the putative oncogene LMO2 [1]. A third child has also been demonstrated to have an integration in LMO2, but is as of yet nonsymptomatic [2]. It is a bit difficult to explain the high frequency of integrations into the same gene using a random model of retroviral integration, and there has been evidence for decades that retroviral integrations may not be random. But the data were somewhat limited in their power to determine the precise nature of the integration biases. The completion of the human genome sequence coupled with sensitive polymerase chain reaction techniques and an ever-decreasing cost of sequencing has given a powerful new tool to the study of integration site selection. In this review, we describe the findings from several recent global surveys of target site selection by retroviruses and transposable elements, and discuss the possible ramifications of these findings to both mechanisms of action and to the use of these elements as gene therapy vectors.

Animals↗
PubMed2004

The phosphatidylinositol-3 kinase pathway regulates bladder cancer cell invasion.

OBJECTIVES: To investigate the role of the phosphatidylinositol (PI)-3 kinase pathway in the invasion of bladder cancer cell lines, and to assess the activation of this pathway in primary human bladder tumours. MATERIALS AND METHODS: Human bladder cancer cells were treated with pathway specific inhibitors or were transfected with PI-3 kinase pathway components. The invasion of cultured bladder cancer cells was analysed by an invasion assay. Bladder cancer cells lines and primary human bladder tumours were analysed for pathway activation by western blotting. RESULTS: A specific inhibitor of PI-3 kinase enzyme activity, Ly294002, potently suppressed the invasive properties of three highly invasive bladder tumour cell lines. Restoration of the PTEN gene to invasive UM-UC-3 bladder tumour cells or expression of a dominant-negative version of the PI-3 kinase target, Akt, also potently inhibited invasion, indicating a central role for the PI-3 kinase/Akt pathway in this process. In addition, 55% of primary tumours from patients with bladder cancer had markedly high levels of phosphorylated Akt. CONCLUSION: Pharmacological or biochemical inhibition of the PI-3 kinase pathway drastically reduced the invasive capacity of bladder cancer cell lines; over half of primary human bladder tumours had high Akt phosphorylation, suggesting that the aberrant activation of this pathway may contribute to the invasion of a significant subset of bladder cancers.

Cell Line, Tumor↗
PubMed2004

Tumor specific novel taxoid-monoclonal antibody conjugates.

The basic principle of the targeted delivery approach is that the conjugation of a drug to a tumor-specific molecule renders the drug inactive until it reaches the target site. Monoclonal antibodies (mAbs), which have shown high binding specificity for tumor-specific antigens, could be used as targeting agents. Paclitaxel has brought significant impact on the current cancer chemotherapy, but seriously suffers from the lack of tumor specificity. A series of paclitaxel-monoclonal antibody conjugates via C-2' ester linkage were reported. Taking into account the fact that the cytotoxicity of paclitaxel is not good enough and thus not applicable to this target delivery prodrug approach, new taxoids bearing methyldisulfanyl(alkanoyl) groups were designed, synthesized, and their activities evaluated. A highly cytotoxic C-10 methyldisulfanyl-propanoyl taxoid, was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR). These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in SCID mice, resulting in complete inhibition of tumor growth in all the treated mice without any noticeable toxicity to the animals.

Animals↗
PubMed2004

Cellular physiology of mismatch repair.

The DNA mismatch repair system maintains genomic stability by correcting DNA sequence errors generated during DNA replication, during genetic exchanges between chromosomes i.e., recombination, and by correcting DNA lesions caused by mutagenic agents such as cis-platinum. Post-synthesis mismatch repair improves almost 1000-fold the fidelity of DNA replication; however, the functions of mismatch repair proteins extend well beyond DNA repair. Recent studies suggest that mismatch repair is part of the machinery that couples DNA damage and repair to cell cycle regulation and apoptosis. These studies indicate that tolerance to certain DNA lesions (such as methylation and cis-platinum adducts) is associated with inefficient activation of cell cycle checkpoints and inefficient activation of apoptosis in mismatch repair deficient cells. Hence, mismatch repair proteins regulate the survival threshold to DNA damage, and this function provides a novel platform for understanding the role of mismatch repair in B cells, in tumor formation, as well as in resistance to chemotherapy. In this communication, we review how mismatch repair may contribute to the physiology of cells and may be regulated by the intracellular trafficking of mismatch repair proteins.

Animals↗
PubMed2003

Molecular cloning and expression of a Kv1.1-like potassium channel from the electric organ of Electrophorus electricus.

Electrocytes from the electric organ of Electrophorus electricus exhibited sodium action potentials that have been proposed to be repolarized by leak currents and not by outward voltage-gated potassium currents. However, patch-clamp recordings have suggested that electrocytes may contain a very low density of voltage-gated K(+) channels. We report here the cloning of a K(+) channel from an eel electric organ cDNA library, which, when expressed in mammalian tissue culture cells, displayed delayed-rectifier K(+) channel characteristics. The amino-acid sequence of the eel K(+) channel had the highest identity to Kv1.1 potassium channels. However, different important functional regions of eel Kv1.1 had higher amino-acid identity to other Kv1 members, for example, the eel Kv1.1 S4-S5 region was identical to Kv1.5 and Kv1.6. Northern blot analysis indicated that eel Kv1.1 mRNA was expressed at appreciable levels in the electric organ but it was not detected in eel brain, muscle, or cardiac tissue. Because electrocytes do not express robust outward voltage-gated potassium currents we speculate that eel Kv1.1 channels are chronically inhibited in the electric organ and may be functionally recruited by an unknown mechanism.

Amino Acid Sequence↗
PubMed2003

Expression of estrogen receptor-alpha and -beta in anterior vaginal walls of genuine stress incontinent women.

Our objective was to study the expression of estrogen receptor (ER) isoforms, ER-alpha and ER-beta, in the anterior vaginal wall of menopausal and fertile women with genuine stress incontinence (SI) by immunohistochemistry and Western blot analysis. Eighteen menopausal women with SI who either were or were not taking estrogen/progestin replacement therapy and 14 fertile women with SI who either were or were not taking contraceptives were enrolled in the study. Biopsies from the suburethral anterior vaginal wall were obtained at tension-free vaginal tape (TVT) operation. Monoclonal antibody to ER-alpha and polyclonal antibody to ER-beta were used to stain frozen sections of vaginal tissue. The receptor expressions were scored based on percentage of positive cells. ER-alpha was detected in vaginal epithelial, stromal and smooth muscle cells. In menopausal SI women ER-alpha was detected significantly more frequently in the vaginal walls of estrogen/progestin-treated patients than in those who were untreated. Fertile SI women had significantly higher expression of ER-alpha than menopausal SI women. ER-alpha was not observed in vaginal blood vessels. ER-beta was detected in epithelial and vascular smooth muscle cells of the vagina. No significant difference in ER-beta expression was observed between different groups of patients. The expression of ER-alpha was not correlated with that of ER-beta. Both ER-alpha and -beta were detected, indicating a potential role for both types of estrogen receptor in the human vaginal wall. The expression of ER-alpha, but not of ER-beta, in menopausal SI women was regulated by estrogen/progestin replacement therapy. The presence of ER-beta in vaginal vascular smooth muscle cells raises the possibility of vascular effects of estrogen on the human vaginal wall.

Adult↗
PubMed2003

Prevalence of diabetes and impaired fasting glucose in the Chinese adult population: International Collaborative Study of Cardiovascular Disease in Asia (InterASIA).

AIMS/HYPOTHESIS: To estimate the prevalence of diagnosed and undiagnosed diabetes and impaired fasting glucose in the general adult population of China. METHODS: The International Collaborative Study of Cardiovascular Disease in ASIA, conducted from 2000 to 2001, included a nationally representative sample of 15 540 adults, aged 35 to 74 years. An overnight fasting blood specimen was collected to measure serum glucose and information on history of diabetes and use of hypoglycaemic medications was obtained by a standard questionnaire. Undiagnosed diabetes (fasting glucose > or =7.0 mmol/l) and impaired fasting glucose (6.1-6.9 mmol/l) were defined using the American Diabetes Association criteria. RESULTS: Prevalence of self-reported diagnosed diabetes, undiagnosed diabetes, and impaired fasting glucose in Chinese adults were 1.3%, 4.2%, and 7.3%, respectively. Overall, 5.2% or 12.7 million men and 5.8% or 13.3 million women in China aged 35 to 74 years had diabetes (self-reported diagnosis plus undiagnosed diabetes). The age-standardized prevalence of diabetes was higher in residents of northern compared to southern China (7.4% vs 5.4%, p<0.001) and in those living in urban compared to rural areas (7.8% vs 5.1%, p<0.001). CONCLUSIONS/INTERPRETATION: Our results show that the prevalence of diabetes in the adult population in China is much higher than previously reported. Three out of every four diabetes patients are undiagnosed, indicative of a lack of population-based screening programmmes and a relatively rapid and recent increase in incidence of diabetes. These results indicate that diabetes has become a major public health problem in China and underscore the need for national strategies aimed at prevention and treatment of diabetes.

Adult↗
PubMed2003

ATP augments peptide release from rat sensory neurons in culture through activation of P2Y receptors.

ATP has recently emerged as an important proinflammatory mediator that has direct excitatory actions on sensory neurons through activation of ion channel-coupled P2X receptors. The purpose of the current work is to assess whether ATP alters the release of neuropeptides from sensory neurons and the receptors mediating this putative action. Exposing embryonic sensory neurons in culture to concentrations of ATP up to 300 microm did not increase the release of immunoreactive substance P or calcitonin gene-related peptide from sensory neurons. However, pre-exposing sensory neurons to 0.1 to 100 microm ATP prior to and throughout administration of 30 nM capsaicin resulted in a significant augmentation of release evoked by the vanilloid. This sensitizing action of ATP is blocked by suramin but not pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid and is mimicked by the P2Y receptor agonists, 2-2-chloroadenosine triphosphate and UTP, but not by 2-(methylthio)adenosine 5'-triphosphate or alpha,beta-methyleneadenosine 5'-diphosphate. This profile of drug actions suggests that the sensitizing actions of ATP are mediated by P2Y receptors. Pretreating sensory neurons with bisindolylmaleimide I, a selective protein kinase C (PKC) inhibitor, attenuates the augmentation of capsaicin-induced peptide release by ATP, further implicating P2Y receptors in the actions of ATP. Immunoblotting also indicates the presence of P2Y2-like immunoreactive substance in embryonic dorsal root ganglia neurons. Together, these data support the notion that ATP acts at P2Y receptors in sensory neurons in a PKC-dependent manner to augment their sensitivity to other stimuli.

Adenosine Triphosphate↗
PubMed2003

Malondialdehyde-protein adducts in the spleens of aniline-treated rats: immunochemical detection and localization.

Previously it was reported that aniline exposure in rats induces increased lipid peroxidation and formation of malondialdehyde (MDA)-protein adducts in the spleen. In order to further elucidate the role of MDA-protein adducts in the splenic toxicity of aniline, studies were conducted to detect and localize these adducts in the spleen. Rabbit polyclonal antisera to MDA-keyhole limpet hemocyanin were employed for immunohistochemical localization and Western blot analyses of MDA-protein adducts in the spleens of aniline-treated (65 mg/kg/d aniline in the drinking water for 30 d) and control rats. For immunohistochemical localization of MDA-protein adducts in the spleen, a new approach using alkaline phosphatase-fast red (red color) to demonstrate bound primary antibodies was adopted, providing a sharper and increased contrast compared to horseradish peroxidase-diaminobenzidine (brown color) methodology. This new approach allowed us to differentiate the changes in aniline-treated spleens, which had extensive brownish deposits of iron proteins. Spleens from aniline-treated rats showed intense staining for these adducts in the red pulp areas (where iron was also localized), especially within the sinusoidal macrophages. Spleens from control rats showed only mild staining for adducts and only traces of iron. Western blot analyses of splenic microsomal proteins from aniline-treated and control rats showed the presence of 13 different MDA-modified proteins. However, 26-, 32-, and 14-kD proteins were more prominent in the aniline-treated rats. The colocalization of MDA-protein adducts with iron in the red pulp of the spleen suggests that iron-catalyzed lipid peroxidation leading to formation of MDA-protein adducts could be a potential mechanism for splenic toxicity of aniline.

Aniline Compounds↗
PubMed2003

Roles of 5-lipoxygenase activating protein in cell proliferation and apoptosis.

5-Lipoxygenase activating protein (FLAP) functions as a facilitator of 5-lipoxygenase (5-LOX) activity. However, on the basis of the induction of apoptosis by the FLAP inhibitor MK886 in cells lacking 5-LOX, it is possible that this fatty acid-binding protein has other activities. This study was designed to examine potential roles of FLAP in apoptosis and cell proliferation. Overexpression of FLAP protein (2.2-fold) was achieved by stable transfection of IL-3-dependent murine prolymphoid progenitor cells (FL5.12) with a construct expressing the cDNA under a CMV promoter. The overexpressed protein was localized to nuclear membranes as with endogenous FLAP. The initial growth rate of FLAP-transfected cells was greater than that of control cells. After 48 h, when cell density had increased, the growth rate of FLAP-transfected cells declined substantially and there and there was a decrease in viability relative to control transfected cells. The FLAP-transfected cells were also more susceptible to withdrawal of IL-3 than were control cells. There was, however, no difference between FLAP and control cells in their susceptibility to MK886, NDGA, or etoposide during the log growth phase. Overexpression of FLAP did not alter Bcl-xL protein expression, but did decrease Bax protein and somewhat increased COX-1 and COX-2 mRNA levels. The failure of increased FLAP to alter susceptibility to MK886 provides further support to the concept that this agent induces apoptosis by mechanisms unrelated to FLAP. The data also suggest that FLAP can affect cell proliferation.

5-Lipoxygenase-Activating Proteins↗
PubMed2003

Enzymatic deglycation with amadoriase enzymes from Aspergillus sp. as a potential strategy against the complications of diabetes and aging.

The Amadori compound is the major single modification of the extracellular matrix by the Maillard reaction in vivo. It is also a source of biologically active glycoxidation products and the formation of glucosepane, the major protein cross-link found in biological tissues so far. For this reason, introduction of deglycating enzymes as anti-aging strategy would be desirable. This article provides an update on amadoriase enzymes from fungi which, one day, will hopefully help prevent the in vivo consequences of glycation.

Aging↗