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Biomedical subjects

X Wen

Publications and source records attributed to X Wen.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Detection of Escherichia coli strains harboring pathogenicity island of Yersinia enterolitica in diarrheal patients and animals in China].

OBJECTIVE: To investigate the prevalence of Escherichia coil strains harboring high pathogenicity island of Yersinia enterocolitica in diarrhea patients, animals, food samples and resulted clinical symptoms. METHODS: Colony hybridization, DNA dot hybridization and polymerase chain reaction (PCR) were used. RESULTS: HPI - harboring E. coli were found in the strains isolated in various provinces of China. The isolation rates were 27.05% (436/1,612) in the strains isolated from diarrhea patients, 10.23% (9/88) in the strains isolated from food samples and 5.71% (16/280) in the strains isolated from feces of cattle and pigs. Typical clinical symptoms of diarrhea caused by HPI - harboring E, coli were inappetency, abdominal pain, shiver and vapidity. Patient's temperature was usually normal or low. Over six episodes of diarrhea was frequently observed, of which most were unformed stools with mucous. CONCLUSION: E. coli strains harboring high - pathogenicity - island of Yersinia species were frequently isolated from diarrhea patients, animals and food samples as well, which might be one of the major causes of diarrhea in China.

Animals↗
PubMed1999

Kinase activation of the non-receptor tyrosine kinase Etk/BMX alone is sufficient to transactivate STAT-mediated gene expression in salivary and lung epithelial cells.

Etk/BMX is a non-receptor protein tyrosine kinase that requires a functional phosphatidylinositol 3-kinase via the pleckstrin homology domain to be activated by cytokine. In the present study, a conditionally active form of Etk was constructed by fusing the hormone-binding domain of estrogen receptor (ER) to an amino terminus truncated form of Etk, PHDelta1-68Etk, to generate DeltaEtk:ER. In stably transfected Pa-4DeltaEtk:ER cells, the activity of DeltaEtk:ER was stimulated within minutes by the treatment of DeltaEtk:ER stimulant, estradiol, and sustained for greater than 24 h. A robust induction in the phosphorylation of signal transducers and activators of transcription (STAT) proteins, including STAT1, STAT3, and STAT5, was accompanied with DeltaEtk:ER activation. Moreover, the conditionally activated Etk stimulated STAT1- and STAT5-dependent reporter activities by approximately 160- and approximately 15-fold, respectively, however, elicited only a modest STAT3-mediated reporter activation. Qualitatively comparable results were obtained in lung A549 cells, indicating that DeltaEtk:ER inducible system could function in an analogous fashion in different epithelial cells. Furthermore, we demonstrated that Etk activation alone augmented cyclin D1 promoter/enhancer activity via its STAT5 response element in both Pa-4DeltaEtk:ER and A549 cells. Altogether, these findings support the notion that the activation of Etk kinase is sufficient to transactivate STAT-mediated gene expression. Hence, our inducible DeltaEtk:ER system represents a novel approach to investigate the biochemical events following Etk activation and to evaluate the contribution by kinase activation of Etk alone or in conjunction with other signaling pathway(s) to the ultimate biological responses.

Animals↗
PubMed1999

GABAA receptor subunit composition and functional properties of Cl- channels with differential sensitivity to zolpidem in embryonic rat hippocampal cells.

Using flow cytometry in conjunction with a voltage-sensitive fluorescent indicator dye (oxonol), we have identified and separated embryonic hippocampal cells according to the sensitivity of their functionally expressed GABAA receptors to zolpidem. Immunocytochemical and RT-PCR analysis of sorted zolpidem-sensitive (ZS) and zolpidem-insensitive (ZI) subpopulations identified ZS cells as postmitotic, differentiating neurons expressing alpha2, alpha4, alpha5, beta1, beta2, beta3, gamma1, gamma2, and gamma3 GABAA receptor subunits, whereas the ZI cells were neuroepithelial cells or newly postmitotic neurons, expressing predominantly alpha4, alpha5, beta1, and gamma2 subunits. Fluctuation analyses of macroscopic Cl- currents evoked by GABA revealed three kinetic components of GABAA receptor/Cl- channel activity in both subpopulations. We focused our study on ZI cells, which exhibited a limited number of subunits and functional channels, to directly correlate subunit composition with channel properties. Biophysical analyses of GABA-activated Cl- currents in ZI cells revealed two types of receptor-coupled channel properties: one comprising short-lasting openings, high affinity for GABA, and low sensitivity to diazepam, and the other with long-lasting openings, low affinity for GABA, and high sensitivity to diazepam. Both types of channel activity were found in the same cell. Channel kinetics were well modeled by fitting dwell time distributions to biliganded activation and included two open and five closed states. We propose that short- and long-lasting openings correspond to GABAA receptor/Cl- channels containing alpha4beta1gamma2 and alpha5beta1gamma2 subunits, respectively.

Animals↗
PubMed1999

Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration.

During cortical development, embryonic neurons migrate from germinal zones near the ventricle into the cortical plate, where they organize into layers. Mechanisms that direct neuronal migration may include molecules that act as chemoattractants. In rats, GABA, which localizes near the target destination for migrating cortical neurons, stimulates embryonic neuronal migration in vitro. In mice, glutamate is highly localized near the target destinations for migrating cortical neurons. Glutamate-induced migration of murine embryonic cortical cells was evaluated in cell dissociates and cortical slice cultures. In dissociates, the chemotropic effects of glutamate were 10-fold greater than the effects of GABA, demonstrating that for murine cortical cells, glutamate is a more potent chemoattractant than GABA. Thus, cortical chemoattractants appear to differ between species. Micromolar glutamate stimulated neuronal chemotaxis that was mimicked by microM NMDA but not by other ionotropic glutamate receptor agonists (AMPA, kainate, quisqualate). Responding cells were primarily derived from immature cortical regions [ventricular zone (vz)/subventricular zone (svz)]. Bromodeoxyuridine (BrdU) pulse labeling of cortical slices cultured in NMDA antagonists (microM MK801 or APV) revealed that antagonist exposure blocked the migration of BrdU-positive cells from the vz/svz into the cortical plate. PCR confirmed the presence of NMDA receptor expression in vz/svz cells, whereas electrophysiology and Ca2+ imaging demonstrated that vz/svz cells exhibited physiological responses to NMDA. These studies indicate that, in mice, glutamate may serve as a chemoattractant for neurons in the developing cortex, signaling cells to migrate into the cortical plate via NMDA receptor activation.

Animals↗
PubMed1999

Mobilization of heavy metals from Le An River sediment.

The release of sediment-bound heavy metals can have a significant influence on river water quality. Generally speaking, variations of pH and oxygen are among the most important chemical factors that affect the mobility of sediment-bound metals. Recent research has indicated that sulfide, measured as acid-volatile sulfide (AVS), is an important partitioning component of heavy metals. We determined the metal release potential of sediments from the Le An River which receives drainage from a major copper mining operation. We found that the in-situ Cu, Pb, Zn, Cd and As concentrations of the Le An River sediments below the mine are much higher than are the global background values, but that Ni was not elevated. There is potential for mobilization of bound metals to the overlying water, the order of metal release ratio in terms of pH dependencies is Zn > Cu > Cd approximately Pb. Sulfide is not a major binding component for metals in Le An River sediment. It is more likely that the iron and manganese oxides are the most important metal binding components in the sediments of the Le An River.

China↗
PubMed1999

High-level expression of I kappa B-beta in the surface epithelium of the colon: in vitro evidence for an immunomodulatory role.

The intestinal epithelium is spatially segregated into two compartments, one containing undifferentiated cells in a proliferative state and one with non-proliferative differentiated cells. Although this epithelium can produce many immunemodulating substances, emerging evidence suggests that the differentiated cell compartment is less immune responsive. Indeed, it is the differentiated cellular compartment that represents the interface between the highly antigenic luminal environment and the mucosal immune system. The NF-kappaB/rel family of transcriptional activators play a critical role in regulating the inflammatory response by activating a wide variety of immune-modulating genes. These transcription factors are maintained in an inactive state in the cytoplasmic compartment by interaction with inhibitory proteins of the IkappaB family. In this study we show by immunohistochemistry that IkappaB-beta is expressed at high levels specifically in the differentiated surface epithelium of the colonic mucosa. Using a naturally occurring compound found in the colon of vertebrates, butyrate, we provide evidence in an intestinal cell line that alteration of IkappaB-beta expression can modulate the transcriptional activation of the interleukin-8 (IL-8) gene by preventing the nuclear translocation of NF-kappaB proteins. Therefore, the expression of IkappaB-beta in the differentiated surface epithelium of the colon may help these cells act as an immunological barrier to prevent activation of the mucosal immune system.

Adjuvants, Immunologic↗
PubMed1999

Mibefradil but not isradipine substantially elevates the plasma concentrations of the CYP3A4 substrate triazolam.

BACKGROUND: The calcium channel blockers mibefradil and isradipine inhibit CYP3A4 in vitro. However, their in vivo inhibitory effects on CYP3A4 are not known in detail, although mibefradil was recently withdrawn from the market because of serious drug interactions. METHODS: The effects of mibefradil and isradipine on the pharmacokinetics and pharmacodynamics of oral triazolam, a model substrate of CYP3A4, were studied in a randomized, double-blind crossover study with three phases. Nine healthy subjects took 50 mg mibefradil, 5 mg isradipine, or placebo orally once a day for 3 days. On day 3, each subject received a single 0.25 mg oral dose of triazolam. Thereafter, blood samples were collected up to 18 hours, and pharmacodynamic effects of triazolam were measured up to 8 hours. RESULTS: Mibefradil increased the total area under the plasma triazolam concentration-time curve [AUC(0 - infinity)] 9-fold compared with placebo (P < .001). The peak plasma concentration of triazolam was increased 1.8-fold (3.4+/-0.1 ng/mL versus 1.8+/-0.2 ng/mL [mean +/- SEM]; P < .001), and the elimination half-life (t 1/2) was increased 4.9-fold (18.5+/-1.9 hours versus 4.0+/-0.5 hours; P < .001) by mibefradil. In addition, mibefradil was associated with increased pharmacodynamic effects of triazolam. In contrast to mibefradil, isradipine reduced the AUC(0 - infinity) and t 1/2 of triazolam by about 20% (P < .05) and had no significant effects on the pharmacodynamics of triazolam. CONCLUSION: Mibefradil but not isradipine markedly increases the plasma concentrations of triazolam and thereby enhances and prolongs its pharmacodynamic effects, consistent with potent inhibition of CYP3A4.

Administration, Oral↗
PubMed1999

Midazolam alpha-hydroxylation by human liver microsomes in vitro: inhibition by calcium channel blockers, itraconazole and ketoconazole.

The inhibitory effects of five calcium channel blockers (diltiazem, isradipine, mibefradil, nifedipine and verapamil) and three azole antifungal agents (itraconazole, hydroxyitraconazole and ketoconazole) on the alpha-hydroxylation of midazolam, a probe drug for CYP3A4-mediated interactions in humans, were studied in vitro using human liver microsomes. IC50 and Ki values were determined for each inhibitor. The kinetics of the formation of alpha-hydroxymidazolam were best described by simple Michaelis-Menten kinetics. The estimated values of Vmax and Km were 696 pmol min.-(1) mg(-1) and 7.46 micromol l(-1), respectively. All the compounds studied inhibited midazolam alpha-hydroxylation activity in a concentration-dependent manner, but there were marked differences in their relative inhibitory potency. Ketoconazole was the most potent inhibitor of midazolam alpha-hydroxylation (IC50 0.12 micromol l (-1)), being 10 times more potent than itraconazole (IC50 1.2 micromol l(-1)). The inhibitory effect of hydroxyitraconazole (IC50 2.3 micromol l (-1) was almost as large as that of itraconazole. Among the calcium channel blockers, mibefradil was the most potent inhibitor of the alpha-hydroxylation of midazolam, with an IC50 value (1.6 micromol l (-1)) similar to that of itraconazole. The other calcium channel blockers were much weaker inhibitors than mibefradil: verapamil exhibited a modest inhibitory effect with an IC50 of 23 micromol l(-1), while isradipine, nifedipine and diltiazem, with IC50 values ranging from 57 to >100 micromol l (-1), were weak inhibitors. This rank order of potency against the alpha-hydroxylation Qf midazolam was verified by the Ki values. With the exception of diltiazem, these in vitro results conform with the observed interaction potential of these agents with midazolam and many other CYP3A4 substrates in vivo in man.

Antifungal Agents↗
PubMed1999

Fluvoxamine is a more potent inhibitor of lidocaine metabolism than ketoconazole and erythromycin in vitro.

CYP3A4 is generally believed to be the major CYP enzyme involved in the biotransformation of lidocaine in man; however, recent in vivo studies suggest that this may not be the case. We have examined the effects of the CYP3A4 inhibitors erythromycin and ketoconazole and the CYP1A2 inhibitor fluvoxamine on the N-deethylation, i.e. formation of monoethylglycinexylidide (MEGX), and 3-hydroxylation of lidocaine by human liver microsomes. The experiments were carried out at lidocaine concentrations of 5 microM (clinically relevant concentration) and 800 microM. The formation of both MEGX and 3-hydroxylidocaine was best described by a two-enzyme model. At 5 microM of lidocaine, fluvoxamine was a potent inhibitor of the formation of MEGX (IC50 1.2 microM). Ketoconazole and erythromycin also showed an inhibitory effect on MEGX formation, but ketoconazole (IC50 8.5 microM) was a much more potent inhibitor than erythromycin (IC50 200 microM). At 800 microM of lidocaine, fluvoxamine (IC50 20.7 microM) and ketoconazole (IC50 20.4 microM) displayed a modest inhibitory effect on MEGX formation, whereas erythromycin was a weak inhibitor (IC50 >250 microM). The 3-hydroxylation of lidocaine was potently inhibited by fluvoxamine at both lidocaine concentrations (IC50 0.16 microM at 5 microM and 1.8 microM at 800 microM). Erythromycin and ketoconazole showed a clear inhibitory effect on the 3-hydroxylation of lidocaine at 5 microM of lidocaine (IC50 9.9 microM and 13.9 microM, respectively), but did not show a consistent effect at 800 microM of lidocaine (IC50 >250 microM and 75.0 microM, respectively). Although further studies are needed to elucidate the role of distinct CYP enzymes in the biotransformation of lidocaine in humans, the findings of this study suggest that while both CYP1A2 and CYP3A4 are involved in the metabolism of lidocaine by human liver microsomes, CYP1A2 is the more important isoform at clinically relevant lidocaine concentrations.

Anesthetics, Local↗
PubMed1999

Linear modeling of mRNA expression levels during CNS development and injury.

Large-scale gene expression data sets are revolutionizing the field of functional genomics. However, few data analysis techniques fully exploit this entirely new class of data. We present a linear modeling approach that allows one to infer interactions between all the genes included in the data set. The resulting model can be used to generate interesting hypotheses to direct further experiments.

Animals↗
PubMed1999

A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily originally shown to play a critical role in adipocyte differentiation and glucose homeostasis, has recently been implicated as a regulator of cellular proliferation and inflammatory responses. Colonic epithelial cells, which express high levels of PPAR-gamma protein, have the ability to produce inflammatory cytokines that may play a role in inflammatory bowel disease (IBD). We report here that PPAR-gamma ligands dramatically attenuate cytokine gene expression in colon cancer cell lines by inhibiting the activation of nuclear factor-kappaB via an IkappaB-alpha-dependent mechanism. Moreover, thiazolidinedione ligands for PPAR-gamma markedly reduce colonic inflammation in a mouse model of IBD. These results suggest that colonic PPAR-gamma may be a therapeutic target in humans suffering from IBD.

Animals↗
PubMed1999

[Antagonistic effects of metallothionein on genetic damage caused by gamma-rays and mitomycin C].

OBJECTIVE: To study the antagonistic effects of metallothionein (Zn-MT)on genetic damage caused by gamma-rays and mitomycin C (MMC) in the liver of rabbits. METHODS: Micronucleus test and DNA strand breaks were determined in vitro and in vivo with single-cell gel electrophoresis assay to observe the effects of Zn-MT on the micronucleus formation and cleavage of DNA chain before and after gamma-rays radiation and MMC treatment. RESULTS: A dose of 664 microg/kg of Zn-MT could inhibit micronucleus formation in the bone marrow of the mice induced by 5 Gy gamma-rays radiation (P < 0.05). Concentrations of 10 and 50 microg/ml Zn-MT could antagonize the increase in bimicronucleus frequency in g12 cells induced by 1 and 3 Gy gamma-rays radiation and 0.3 microg/ml MMC treatment (P < 0.05 or P < 0.01). A dose of 50 microg/ml Zn-MT could reduce the DNA single strand breaks caused by 1 Gy gamma-rays radiation, but without statistical significance (P > 0.05). CONCLUSION: Zn-MT could antagonize the genetic damage to certain extent in the liver of the rabbits caused by gamma-rays radiation and MMC treatment.

Animals↗
PubMed1999

[Effects of Squama manitis on cardiac systolic function and platelet aggregation].

OBJECTIVE: To study the effect of Squama Manitis(S. M.) on cardiac function and platelet aggregation in vitro. METHOD: Isolated working rat hearts were prepared, and cardiac performance was measured before and after adding S. M. in the Krebs-Hensleit(K-H) perfusion buffer. Controls with K-H buffer were also investigated. Rich platelet plasma and Poor platelet plasma were centrifuged from the blood of 15 patients with coronary heart disease. Each sample was divided into three parts for use by three groups: control, group of S. M. and group of aspirin. Platelet aggregation was stimulated by adenosine diphosphate. RESULT: LVSP, +dP/dtmax and CO of isolated working rat hearts were significantly increased after treating with S. M. liquor. S. M. had no obvious effect on -dP/dtmax and LVEDP. These parameters did not change significantly in the control. Percentages of platelet aggregation were significantly lower in the group of S. M. and the group of aspirin as compared with the control. CONCLUSION: S. M. increases cardiac systolic function, has positive inotropic effect on myocardium and inhibits platelet aggregation.

Animals↗
PubMed1999

[Study on correlation between in vivo and in vitro tests of biomaterials--correlation between leukocyte chemotaxis test and muscular implant test in rabbits].

The purpose of this study was to investigate the correlation between the results of in vivo and in vitro tests of biomaterials. With muscular implant test and leukocyte chemotaxis test, the levels of tissue toxicity of seven biomaterials were evaluated. The samples with high-level toxicity showed weak leukocyte chemotaxis, which would influence the anti-inflammatory reaction to foreign bodies. By the method of Spearman rank correlation, the coefficient was between 0.89286-0.98198 indicating that the correlation of the two tests is excellent.

Animals↗
PubMed1999

[Evaluation on cytotoxicity of gallium alloy].

Cytotoxicity is an important indicator to the biocompatibility of biomaterials. In this study, the cytotoxicity of Gallium alloy was evaluated by the method of cell relative growth rate in vitrousing L-929 mouse fibroblast. The cell relative growth rate of Gallium alloy was the absorbency ratio between the solution of Gallium alloy and negative control. The relative growth rates of Gallium aloy were converted into the scores of cytotoxicity. It was found from the results that Gallium alloy had no cytotoxicity.

Alloys↗
PubMed1998

The glycogen phosphorylase-2 promoter binding protein in Dictyostelium is replication protein A.

During Dictyostelium development, glycogen degradation is a crucial event that provides glucose monomers used in the synthesis of the essential structural components for cellular differentiation. The product of the developmentally regulated glycogen phosphorylase-2 gene (gp2) catalyzes the degradation. DNA-binding proteins were found to bind to a regulatory site of the gp2 gene in a stage-dependent pattern. Gel-shift analysis of undifferentiated amoebae cell extract revealed a protein migrating at 0.40 Rf, while 17 hour differentiated cell extract produced a species migrating at 0.32 Rf. Both the 0.32 and 0.40 Rf proteins were purified and found to consist of three subunits of 18, 35 and 62 kDa (for 0.40 Rf) or 81 kDa (for 0.32 Rf). Data base searches identified the protein as the Dictyostelium homologue of replication protein A (DdRPA). Amino acid sequence analysis showed identity between the 62 and 81 kDa subunits. Incubation of cell-free extracts under appropriate conditions at low pH, resulted in conversion of the 81 kDa to the 62 kDa subunit. Northern blot analysis revealed that the levels of expression of the large subunit of DdRPA were constant throughout differentiation and the size of the mRNA was the same at all stages of development. The results raise the possibility that pH induced post-translational modifications of DdRPA are involved in events that halt cell proliferation and induce differentiation in Dictyostelium.

Amino Acid Sequence↗
PubMed1998

The amiloride-sensitive epithelial sodium channel alpha-subunit is transcriptionally down-regulated in rat parotid cells by the extracellular signal-regulated protein kinase pathway.

Previous studies have shown that an inducible Raf-1 kinase protein, DeltaRaf-1:ER, activates the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK)-signaling pathway, which is required for the transformation of the rat salivary epithelial cell line, Pa-4. Differential display polymerase chain reaction was employed to search for mRNAs repressed by DeltaRaf-1:ER activation. Through this approach, the gene encoding the alpha-subunit of the amiloride-sensitive epithelial sodium channel (alpha-ENaC) was identified as a target of activated Raf-1 kinases. alpha-ENaC down-regulation could also be seen in cells treated with 12-O-tetradecanoyl-1-phorbol-13-acetate (TPA), indicating that the repression of steady-state alpha-ENaC mRNA level was dependent upon the activity of protein kinase C, the target of TPA, as well. Pretreatment of cells with a specific inhibitor of the ERK kinase pathway, PD 98059, markedly abolished the down-regulation of alpha-ENaC expression, consistent with the hypothesis that the ERK kinase-signaling pathway is involved in TPA-mediated repression. Moreover, through the use of transient transfection assays with alpha-ENaC-reporter and activated Raf expression construct(s), we provide the first evidence that activation of the ERK pathway down-regulates alpha-ENaC expression at the transcriptional level. Elucidating the molecular programming that modulates the expression of the alpha-subunit may provide new insights into the modulation of sodium reabsorption across epithelia.

Animals↗