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Biomedical subjects

X Q Xu

Publications and source records attributed to X Q Xu.

At least 19 recordsLinked to original sources
PubMed2007

HOXA1-stimulated oncogenicity is mediated by selective upregulation of components of the p44/42 MAP kinase pathway in human mammary carcinoma cells.

Expression of homeobox A1 (HOXA1) results in oncogenic transformation of immortalized human mammary epithelial cells with aggressive tumor formation in vivo. However, the mechanisms by which HOXA1 mediates oncogenic transformation is not well defined. To identify molecules that could potentially be involved in HOXA1-mediated oncogenic transformation, microarray analysis was utilized to characterize and compare the gene expression pattern in response to forced expression or depletion of HOXA1 in human mammary carcinoma cells. Gene expression profiling identified that genes involved in the p44/42 mitogen-activated protein (MAP) kinase activation pathway (GRB2, MAP kinase kinase (MEK1) and SDFR1) or p44/42 MAP kinase-regulated genes (IER3, EPAS1, PCNA and catalase) are downstream expression targets of HOXA1. Forced expression of HOXA1 increased GRB2 and MEK1 mRNA and protein expression and increased p44/42 MAP kinase phosphorylation, activity and Elk-1-mediated transcription. Use of a MEK1 inhibitor demonstrated that increased p44/42 MAP kinase activity is required for the HOXA1-mediated increase in cell proliferation, survival, oncogenicity and oncogenic transformation. Thus, modulation of the p44/42 MAP kinase pathway is one mechanism by which HOXA1 mediates oncogenic transformation of the human mammary epithelial cell.

Breast Neoplasms↗
PubMed2004

Blob dynamics in 3D BOUT simulations of tokamak edge turbulence.

Propagating filaments of enhanced plasma density, or blobs, observed in 3D numerical simulations of a diverted, neutral-fueled tokamak are studied. Fluctuations of vorticity, electrical potential phi, temperature Te, and current density J parallel associated with the blobs have a dipole structure perpendicular to the magnetic field and propagate radially with large E x B drift velocities (>1 km/s). The simulation results are consistent with a 3D blob dynamics model that incorporates increased parallel plasma resistivity (from neutral cooling of the X-point region), blob disconnection from the divertor sheath, X-point closure of the current loops, and collisional physics to sustain the phi, Te, J parallel dipoles.

Journal Article↗
PubMed2003

Variation of microcystins in a lake for water supply.

A site investigation was conducted to correlate the relationships between microcystins (MC) concentration and algal growth in Dianchi Lake in China. Laboratory experiments were undertaken to test the effects of sediment adsorption, photoirradiation and biodegradation on microcystins removal. Bioaccumulation of microcystins was also determined using silver carp fish. It was observed that MC concentrations varied in accordance with algae growth in Dianchi Lake. The results obtained in the laboratory demonstrated that the removal of MC with fresh sediments was less than 10%, photoirradiation removed more than 75% MC within two hours, and the biodegradation needed much longer time to produce substantial degradation of MC. The results suggest that bioaccumulation of microcystins in fish was not significant in Dianchi Lake.

Animals↗
PubMed2002

Experimental and theoretical study of quasicoherent fluctuations in enhanced D(alpha) plasmas in the Alcator C-Mod tokamak.

A comparison of experimental measurements and theoretical studies of the quasicoherent (QC) mode, observed at high densities during enhanced D(alpha) (EDA) H mode in the Alcator C-Mod tokamak, are reported. The QC mode is a high frequency ( approximately 100 kHz) nearly sinusoidal fluctuation in density and magnetic field, localized in the steep density gradient ("pedestal") at the plasma edge, with typical wave numbers k(R) approximately 3-6 cm(-1), k(theta) approximately 1.3 cm(-1) (midplane). It is proposed here that the QC mode is a form of resistive ballooning mode known as the resistive X-point mode, in reasonable agreement with predictions by the BOUT (boundary-plasma turbulence) code.

Journal Article↗
PubMed2002

Validation of a two-pool model for the kinetics of beta2-microglobulin.

UNLABELLED: Secondary amyloidosis due to beta-2-microglobulin (beta2-m) is a serious long-term complication in patients on regular dialysis therapy. Beta2-m can be considered a middle-molecule marker used to facilitate the assessment of dialysis efficacy. For this purpose, a validated model that calculates characteristic efficacy parameters, such as Kt/V, TAC and generation rate, is needed. There is general agreement that beta2-m-kinetics should be described by a two-pool model, but little has been published to validate such an approach. We measured the beta2-m concentration profiles of eight stable patients during hemodialysis (HD) at the start of treatment, after 30 minutes, after 60 minutes, and every hour until the end. Thereafter they were measured at 10-minute intervals for an hour. The dialyser clearances were determined from the plasma concentrations in front of and behind the dialyser twice during each session - after 1 hour, and 4 hours from the start of treatment. The kinetic parameters of a two-pool model (e.g. the compartment volumes V1 and V2, the mass transfer coefficient K12 and the generation rate G) were determined from the optimal fit of the measured concentration profile. The table below summarises the results by giving the mean and standard deviation for each parameter: [table: see text]. Inter-individual differences in V1/V2 and K12 were high, ranging from 2.5 to 10.0 for V/V2 and from 26 to 140 for K12. Error analysis suggested that these wide ranges were due to the method and that in reality the probable range of V is 25-36% of TBW, of V1/V2 3.5-5.3, and of K12 30-80 ml/min. With standard values for these three parameters (V = 30% of TBW, V/V2 = 4.4 and K12 = 55 ml/m), equal for all patients, and their respective ranges, Kt/W can be calculated with a standard deviation of 13%. Kt/W > 1.2 secures the maximum possible beta2-m removal with three HD treatments a week. CONCLUSIONS: The parameters of a two-pool model of beta2-m kinetics can be derived from concentration profiles obtained under routine dialysis conditions, but accuracy is not completely satisfactory. Similar to the dialysis dose for urea (Kt/Vurea) the dialysis dose for beta2-m (Kt/Vbeta2-m) can be calculated from the pre- and post-dialysis concentrations of beta2-m, body weight, ultrafiltration and dialysis time. Kt/Vbeta2-m > 1.2 secures the maximum possible removal of beta2-m in HD with three sessions per week.

Adult↗
PubMed2002

Testing protein permeability of dialysis membranes using SDS-PAGE.

BACKGROUND: Permeability of dialysis membranes for high molecular weight compounds should be similar to that of the glomerular membrane in order to remove uremic toxins like the human kidney does. In order to evaluate permeability of high-flux dialysis membranes SDS-PAGE is applied for examination of filtrate of dialysers during routine dialysis with different membranes. METHOD: SDS-PAGE analysis is performed with silver staining method according to the modification of Melzer (5) and consecutive laser densitometry. RESULTS: The protein pattern of filtrate from dialysis membranes is similar to that of the glomerular membrane containing IgG, transferrin, albumin, alpha-1-microglobulin, retinol binding protein and beta-2-microglobulin. Comparing different membranes there are considerable differences depending on cut-off, charge and adsorption capacity of the particular membrane. In all membranes tested permeability of proteins decreases during one treatment session. CONCLUSION: Protein permeability of high-flux dialysis membranes is similar to the gloemerular membrane but modified according to pore-size, surface charge, adsorption and time on dialysis. In contrast to the glomerular membrane in each of the investigated membranes protein permeability decreases during function.

Electrophoresis, Polyacrylamide Gel↗
PubMed2001

Feedback regulation of an Agrobacterium catalase gene katA involved in Agrobacterium-plant interaction.

Catalases are known to detoxify H2O2, a major component of oxidative stress imposed on a cell. An Agrobacterium tumefaciens catalase encoded by a chromosomal gene katA has been implicated as an important virulence factor as it is involved in detoxification of H2O2 released during Agrobacterium-plant interaction. In this paper, we report a feedback regulation pathway that controls the expression of katA in A. tumefaciens cells. We observed that katA could be induced by plant tissue sections and by acidic pH on a minimal medium, which resembles the plant environment that the bacteria encounter during the course of infection. This represents a new regulatory factor for catalase induction in bacteria. More importantly, a feedback regulation was observed when the katA-gfp expression was studied in different genetic backgrounds. We found that introduction of a wild-type katA gene encoding a functional catalase into A. tumefaciens cells could repress the katA-gfp expression over 60-fold. The katA gene could be induced by H2O2 and the encoded catalase could detoxify H2O2. In addition, the katA-gfp expression of one bacterial cell could be repressed by other surrounding catalase-proficient bacterial cells. Furthermore, mutation at katA caused a 10-fold increase of the intracellular H2O2 concentration in the bacteria grown on an acidic pH medium. These results suggest that the endogenous H2O2 generated during A. tumefaciens cell growth could serve as the intracellular and intercellular inducer for the katA gene expression and that the acidic pH could pose an oxidative stress on the bacteria. Surprisingly, one mutated KatA protein, exhibiting no significant catalase activity as a result of the alteration of two important residues at the putative active site, could partially repress the katA-gfp expression. The feedback regulation of the katA gene by both catalase activity and KatA protein could presumably maintain an appropriated level of catalase activity and H2O2 inside A. tumefaciens cells.

Agrobacterium tumefaciens↗
PubMed2001

[Significance of the unbalanced expression of Th1/Th2 type cytokines in human glioma].

OBJECTIVE: To study the significance of the unbalanced expression of Th1/Th2 type cytokines in human glioma. METHODS: The gene expressions of Th1/Th2 type cytokines in 62 specimens of human glioma tissues, 4 glioma cell lines, peripheral blood mononuclear cell (PBMC) of 15 glioma patients, 5 specimens of normal adult brain tissue and 5 brain meningioma tissues were detected by semiquantitative reverse transcription polymerase chain reaction. IFN-gamma and IL-2 represent Th1 type cytokines. IL-4, IL-6, IL-10 and IL-13 represent Th2 type cytokines. RESULTS: There were obviously predominant expression of Th2 type cytokines in glioma cell lines (P < 0.01) and specimens of human glioma tissues (P < 0.01). The tendency of distinct expression of Th2 type cytokines in PBMC was also existent. There wasn't obvious discrepancy of the expression of two type cytokines in normal adult brain tissues and meningioma tissues. CONCLUSIONS: It is likely that the switching of Th1/Th2 type cytokines in gliomas as predominant expression of Th2 type cytokine genes is related to the origination of gliomas and the evasion of glioma cells from immune surveillance.

Adolescent↗
PubMed2000

An Agrobacterium catalase is a virulence factor involved in tumorigenesis.

Most plant pathogenic bacteria adopt the type III secretion systems to secrete virulence factors and/or avirulence gene products, which trigger the plant hypersensitive response (HR) and the oxidative burst with hydrogen peroxide (H2O2) as the main component. However, the soil-borne plant pathogen Agrobacterium tumefaciens uses the type IV secretion pathway to deliver its oncogenic T-DNA that causes crown gall tumours on many plant species. A. tumefaciens does not elicit a typical HR on those plants. Here, we report that inactivation of one of A. tumefaciens catalases (which converts H2O2 to H2O and O2) by a transposon insertion highly attenuated the bacterial ability to cause tumours on plants and to tolerate H2O2 toxicity, but not the bacterial viability in the absence of exogenous H2O2. This provides the first genetic evidence that the Agrobacterium-plant interaction involves a plant defence response, such as H2O2 production, and that catalase is a virulence factor for a plant pathogen.

Amino Acid Sequence↗
PubMed2000

Human Cdc5, a regulator of mitotic entry, can act as a site-specific DNA binding protein.

G(2)/M progression requires coordinated expression of many gene products, but little is known about the transcriptional regulators involved. We recently identified human Cdc5, a positive regulator of G(2)/M in mammalian cells. We also demonstrated the presence of a latent activation domain in its carboxyl terminus, suggesting that human Cdc5 regulates G(2)/M through transcriptional activation. Despite the presence of a DNA binding domain, studies by others have failed to identify a preferential binding site for Cdc5 family members. In addition, Cdc5 recently has been associated with the splicesome in several organisms, suggesting that it may not act through DNA binding. We now report the identification of a 12 bp sequence to which human Cdc5 binds specifically and with high affinity through its amino terminus. We show that this DNA-protein interaction is capable of activating transcription. We also used a selection system in yeast to identify human genomic fragments that interact with human Cdc5. Several of these contained sequences similar to the binding site. We demonstrate that these bind human Cdc5 with similar specificity and affinity. These experiments provide the first evidence that Cdc5 family members can act as site-specific DNA binding proteins, and that human Cdc5 may interact with specific, low abundance sequences in the human genome. This raises the possibility that Cdc5 proteins may participate in more than one process necessary for regulated cell division.

Binding Sites↗
PubMed1996

Lovastatin inhibits the stimulation of mitogen-activated protein kinase by insulin in HIRcB fibroblasts.

Lovastatin, a cholesterol biosynthesis inhibitor, has recently been shown to inhibit mitogenesis and tumor growth. We have investigated the effects of lovastatin on the activation of MAP kinase by insulin using as a model HIRcB cells, a rat fibroblast cell line that overexpresses the human insulin receptor. Treatment with lovastatin (1-30 microM) for 24 h decreased the level of activation of MAP kinase by insulin by as much as 60%. Immunoblotting experiments using a specific anti-MAP kinase monoclonal antibody demonstrated that the amount of MAP kinase protein in the cells was not altered by lovastatin treatment. Likewise, lovastatin had no apparent effects on the expression of the insulin receptor. Treatment with lovastatin (20 microM) reduced the percentage of farnesylated Ras by 50%. Immunoprecipitation of tyrosine phosphorylated proteins from HIRcB cell lysates followed by immunodetection of MAP kinase using specific antibodies demonstrated a reduced level of insulin-induced tyrosine phosphorylation levels of MAP kinase in lovastatin-treated cells. Furthermore, immunodetection of the beta-subunit of the insulin receptor in anti-phosphotyrosine immunoprecipitates revealed that treatment with lovastatin reduced the tyrosine phosphorylation levels of the receptor. Lysates obtained from cells treated with increasing concentrations of lovastatin demonstrated a dose-dependent inhibition of the insulin-induced tyrosine phosphorylation of the receptor. Treatment with mevalonic acid prevented the effects of lovastatin demonstrating that the effects of the drug are a consequence of its inhibitory effects on the synthesis of steroids. It is concluded that, in addition to inhibition of Ras farnesylation, lovastatin reduces receptor tyrosine phosphorylation levels which also contributes to the blockade of MAPK activation by the insulin receptor.

Animals↗
PubMed1995

Brefeldin A inhibits insulin-dependent receptor redistribution in HIRcB cells.

Brefeldin A (BFA) is a potent inhibitor of intracellular vesicle traffic. We have investigated the effects of BFA on the traffic of the insulin receptor in HIRcB cells, a cell line derived from Rat-1 fibroblasts that over-expresses a normal human insulin receptor. We report here that insulin-dependent receptor redistribution is inhibited by BFA and that this drug has no effects on the insulin-dependent redistribution of the receptor. Auto-phosphorylation of the insulin receptor and the stimulation of mitogen-activated protein kinase (MAPK) by insulin were not affected by treatment with the drug. The effects of BFA were further shown to require addition of the drug prior to the addition of insulin. BFA added 10 min after stimulation with insulin had no effects on the redistribution of the receptor. Dose-response studies demonstrated that the effects of BFA were half-maximal at a dose of 1 microgram/ml and maximal at about 10 micrograms/ml. These findings suggest that BFA blocks an early step in the chain of events that lead to insulin receptor internalization without affecting the interactions of the receptor with insulin, the stimulation of the tyrosine kinase activity of the receptor by the hormone, or other insulin-regulated signalling pathways, such as the activation of MAPK.

Animals↗
PubMed1994

Lovastatin disrupts early events in insulin signaling: a potential mechanism of lovastatin's anti-mitogenic activity.

The mechanism by which lovastatin lowers cholesterol levels is well characterized but little is known about its anti-mitogenic and anti-tumorigenic mechanism. Here we demonstrate that lovastatin disrupts early events in the mitogenic signaling pathways of insulin. Insulin treatment (200 mM) of quiescent HIR rat-1 fibroblasts results in an 8-fold stimulation of phosphatidylinositol-3-kinase (PI-3-K) activity. Overnight pretreatment of cells with lovastatin (20 microM) inhibits insulin stimulation of PI-3-K activity by 75%. Immunoprecipitation and immunoblotting experiments using antibodies against the regulatory subunit of PI-3-K (p85), phosphotyrosine, and insulin receptor alpha and beta subunits demonstrate that lovastatin inhibits the association of p85 with tyrosine phosphorylated insulin receptor substrate-1 and the beta subunit of the insulin receptor. Furthermore, lovastatin dramatically reduces (70-100%) the level of tyrosine phosphorylated insulin receptor beta subunit following insulin stimulation. These results clearly demonstrate that lovastatin disrupts early events of insulin mitogenic signaling by reducing the levels of tyrosine phosphorylated beta subunit and suggest that this disruption is a potential mechanism for the anti-mitogenic effect of lovastatin.

Animals↗
PubMed1989

[A retrospective study of 115 cases of fungal pneumonia].

115 cases of immunocompromised patients complicated with fungal pneumonia treated during the period from April 1968 to December 1986 were retrospectively studied. 96 were male and 19 female. Their age ranged from 6 to 84. The incidence increased significantly in recent years especially after 1983. Severe liver disease was the underlying disease in 102 (88.7%) patients. 108 (93.9%) had received antibiotics and 55 (47.9%) corticosteroids. Fungi species isolated were candida in 107 (54.9%), aspergillus in 82 (36.9%), penicillium in 7 (3.6%), mucormycetes in 6 (3%) and reotrichum in 3 (1.5%). Fever, cough, expectoration, moist rales diminished breath sounds and increase of W. B. C. and neutrophils were the important clinical features. The roentgenologic findings vary with the nature and extent of the pathologic process. Disseminated mycoses were found in 9 of the 18 autopsied cases. The characteristic pathologic findings were inflammation, abscess formation, vasculitis, infarction and hemorrhage. Extrapulmonary features such as enteritis, purulent nephritis, abnormal EKG, encephalopathy and rash were present. 93 cases received antifungal therapy including garlicin, clotrimazole, amphotericin B, nystatine, miconazole, 5-fluctosine and ketoconazole. Because these drug combinations were so complex, it is difficult to evaluate their efficiency. However the survival rate was somewhat elevated in recent years. The mortality rate of this series was 80.9%.

Adolescent↗