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Biomedical subjects

Y Xu

Publications and source records attributed to Y Xu.

At least 361 records · Page 20Linked to original sources
PubMed2000

Activity of crude extract of Rubus crataegifolius roots as a potent apoptosis inducer and DNA topoisomerase I inhibitor.

The effects of methanol extract of Rubus crategifolius roots and its solvent fractions were investigated on the proliferation of MCF-7 human breast carcinoma cells. The methanol extract inhibited the proliferation of MCF-7 cells in a concentration dependent manner. Moreover, their methanol soluble (W-M) fraction had the greatest inhibitory effect on the growth of MCF-7 cells. To evaluate whether the W-M fraction affects on the cell cycle of MCF-7 cells, cells treated with this fraction were analyzed with flow cytometry. The W-M fraction increased G0/G1 phase after 24 h-treatment and induced apoptosis after 48 h-treatment. The hallmark of apoptosis, DNA fragmentation, also appeared by W-M fraction after 48 h-treatment. Furthermore, the methanol extract and its W-M fraction inhibited the activity of the topoisomerase I enzyme in the relaxation assay. From these results, their W-M fraction as well as methanol extract of R. crategifolius roots are necessary for further studies as a potent inhibitor of the growth of cancer cells.

Apoptosis↗
PubMed2000

In vitro activity of meropenem and four other antibiotics against 554 clinical strains obtained from Beijing in 1999.

In 1999, a surveillance study was initiated in a hospital in Beijing to monitor the potency and spectrum of five extended-spectrum beta-lactam antimicrobial agents (meropenem, imipenem, cefepime, ceftazidime, and cefoperazone/sulbactam) tested against 554 strains of bacteria. Five groups of organisms were tested by the E-test method, with results validated by concurrent quality control strain analysis. Results were tabulated, and 100% of quality assurance tests (16/16 tests) were within ranges recommended by the National Committee for Clinical Laboratory Standards. Of the five beta-lactam drugs tested, meropenem and imipenem were the most active against all isolates tested. Overall, the rank order of activity of the five agents was: meropenem (94.6% susceptible) > imipenem (90.1%) > cefepime (77.6%), cefoperazone/sulbactam (77.5%), ceftazidime (76.6%). Ninety-five percent of Enterobacter were to meropenem, while 82% were susceptible to imipenem. Meropenem was more active than imipenem against Pseudomonas aeruginosa. The minimum inhibitory concentration (MIC) of meropenem was eightfold lower than that of imipenem. Meropenem had excellent activity against Haemophilus influenzae, Streptococcus pneumoniae, and oxacillin-susceptible staphylococci.

Anti-Bacterial Agents↗
PubMed2000

NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors.

New lines of evidence suggest that volatile anesthetics interact specifically with proteins. Direct binding analysis, however, has been largely limited to soluble proteins. In this study, specific interaction was investigated between isoflurane, a clinically important volatile anesthetic, and membrane-bound nicotinic acetylcholine receptors (nAChRs) from Torpedo electroplax, using (19)F nuclear magnetic resonance spectroscopy and gas chromatography. The receptors were reconstituted into 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid vesicles. After correcting for nonspecific partitioning into the lipid, the equilibrium dissociation constant, K(d), of isoflurane binding to nAChR at 15 degrees C was found to be 0.36 +/- 0.03 mM. This value is within the clinically relevant concentration range of the agent. Based on the receptor concentrations in the vesicle suspension assayed by the bicinchoninic acid method and the fraction of bound isoflurane, X(b), determined by gas chromatography, an estimate of an average of 9-10 specifically bound isoflurane molecules can be made for each receptor, or two for each subunit. Upon binding, the transverse relaxation time constant (T(2)) of (19)F resonance of isoflurane is decreased by nearly three orders of magnitude, indicating a dramatic reduction in the mobility of specifically bound isoflurane. Kinetic analysis reveals that the off rate of binding, k(-1), is 1.7 x 10(4) s(-1). The on rate, k(+1), can thus be calculated to be approximately 4.8 x 10(7) M(-1) s(-1), suggesting a nearly diffusion-limited association. This is in contrast to anesthetic binding to a soluble protein, bovine serum albumin (BSA), where k(+1) and k(-1) are at least an order of magnitude slower. It is concluded that the presence of lipids may be critical for the correct evaluation of binding kinetics between volatile anesthetics and neuronal receptors.

Anesthetics, Inhalation↗
PubMed2000

General anesthetic binding to gramicidin A: the structural requirements.

There is a distinct possibility that general anesthetics exert their action on the postsynaptic receptor channels. The structural requirements for anesthetic binding in transmembrane channels, however, are largely unknown. High-resolution (1)H nuclear magnetic resonance and direct photoaffinity labeling were used in this study to characterize the volatile anesthetic binding sites in gramicidin A (gA) incorporated into sodium dodecyl sulfate (SDS) micelles and into dimyristoylphosphatidylcholine (DMPC) bilayers, respectively. To confirm that the structural arrangement of the peptide side chains can affect anesthetic binding, gA in nonchannel forms in methanol was also analyzed. The addition of volatile anesthetic halothane to gA in SDS with a channel conformation caused a concentration-dependent change in resonant frequencies of the indole amide protons of W9, W11, W13, and W15, with the most profound changes in W9. These frequency changes were observed only for gA carefully prepared to ensure a channel conformation and were absent for gA in methanol. For gA in DMPC bilayers, direct [(14)C]halothane photolabeling and microsequencing demonstrated dominant labeling of W9, less labeling of W11 and W13, and no significant labeling of W15. In methanol, gA showed much less labeling of any residues. Inspection of the 3-D structure of gA suggests that the spatial arrangements of the tryptophan residues in the channel form of gA, combined with the amphiphilic regions of lipid, create a favorable anesthetic binding motif.

Amino Acid Sequence↗
PubMed2000

Peak identification for PCDD/Fs in environmental samples at different temperature programs.

A method has been developed for peak recognition of 136 polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) at different temperature programs. Their retention behaviours are predicted on the basis of an identification database of retention values (A, B) of gas chromatography. By the retention times of 13C labelled 2,3,7,8-substituted PCDD/F internal standards, the retentions of all PCDDs and PCDFs can be calculated. After comparison with the retentions of practical environmental samples, the predicted values have been proved to be very accurate.

Benzofurans↗
PubMed2000

Validation of real-time three-dimensional echocardiography for quantifying left ventricular volumes in the presence of a left ventricular aneurysm: in vitro and in vivo studies.

OBJECTIVES: To validate the accuracy of real-time three-dimensional echocardiography (RT3DE) for quantifying aneurysmal left ventricular (LV) volumes. BACKGROUND: Conventional two-dimensional echocardiography (2DE) has limitations when applied for quantification of LV volumes in patients with LV aneurysms. METHODS: Seven aneurysmal balloons, 15 sheep (5 with chronic LV aneurysms and 10 without LV aneurysms) during 60 different hemodynamic conditions and 29 patients (13 with chronic LV aneurysms and 16 with normal LV) underwent RT3DE and 2DE. Electromagnetic flow meters and magnetic resonance imaging (MRI) served as reference standards in the animals and in the patients, respectively. Rotated apical six-plane method with multiplanar Simpson's rule and apical biplane Simpson's rule were used to determine LV volumes by RT3DE and 2DE, respectively. RESULTS: Both RT3DE and 2DE correlated well with actual volumes for aneurysmal balloons. However, a significantly smaller mean difference (MD) was found between RT3DE and actual volumes (-7 ml for RT3DE vs. 22 ml for 2DE, p = 0.0002). Excellent correlation and agreement between RT3DE and electromagnetic flow meters for LV stroke volumes for animals with aneurysms were observed, while 2DE showed lesser correlation and agreement (r = 0.97, MD = -1.0 ml vs. r = 0.76, MD = 4.4 ml). In patients with LV aneurysms, better correlation and agreement between RT3DE and MRI for LV volumes were obtained (r = 0.99, MD = -28 ml) than between 2DE and MRI (r = 0.91, MD = -49 ml). CONCLUSIONS: For geometrically asymmetric LVs associated with ventricular aneurysms, RT3DE can accurately quantify LV volumes.

Animals↗
PubMed2000

Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.

A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.

Amino Acid Sequence↗
PubMed2000

Integration of medical applications: the 'mediator service' of the SynEx platform.

Interoperability is a key issue and a long-term domain of research for distributed healthcare information systems. The SynEx European project provides open and standard integration platform for both new and legacy medical applications. It aims to provide access to hospital information services, patient records, and to medical knowledge, in a seamless way, hiding the distribution aspects and the heterogeneity of the underlying systems. In this study, we describe the SynEx 'mediator service', a software engineering component, that is used to facilitate the development of mediators between any pair of SynEx components and to manage the corresponding interchange messages. Both a C++ library and a Java package of a generic mediator model are provided with several ready-to-use specialisations for well-defined use. The use of the XML technology as a powerful data interchange format and as an efficient data structure converter is proposed and discussed.

Computer Communication Networks↗
PubMed2000

Identification of metabolites of [1,2,3-(13)C]Propargyl alcohol in mouse urine by (13)C NMR and mass spectrometry and comparison to rat.

Species differences in the metabolism of acetylenic compounds commonly used in the formulation of pharmaceuticals and pesticides have not been investigated. To better understand the in vivo reactivity of this bond, the metabolism of propargyl alcohol (PA), 2-propyn-1-ol, was examined in rats and mice. An earlier study (Banijamali, A. R.; Xu, Y.; Strunk, R. J.; Gay, M. H.; Ellis, M. C.; Putterman, G. J. J. Agric. Food Chem. 1999, 47, 1717-1729) in rats revealed that PA undergoes extensive metabolism primarily via glutathione conjugation. The current research describes the metabolism of PA in CD-1 mice and compares results for the mice to those obtained for rats. [1,2,3-(13)C;2,3-(14)C]PA was administered orally to the mice. Approximately 60% of the dose was excreted in urine by 96 h. Metabolites were identified, directly, in whole urine by 1- and 2-D (13)C NMR and HPLC/MS and by comparison with the available reference compounds. The proposed metabolic pathway involves glucuronide conjugation of PA to form 2-propyn-1-ol-glucuronide as well as oxidation of PA to the proposed intermediate 2-propynal. The aldehyde undergoes conjugation with glutathione followed by further metabolism to yield as final products 3,3-bis[(2-acetylamino-2-carboxyethyl)thio]-1-propanol, 3-[(2-acetylamino-2-carboxyethyl)thio]-3-[(2-amino-2-carboxyethyl)thi o]-1-propanol, 3,3-bis[(2-amino-2-carboxyethyl)thio]-1-propanol, 3-[(2-amino-2-carboxyethyl)thio]-2-propenoic acid, and 3-[(2-formylamino-2-carboxyethyl)thio]-2-propenoic acid. A small portion of 2-propynal is also oxidized to result in the excretion of 2-propynoic acid. On the basis of urinary metabolite data, qualitative and quantitative differences are noted between rats and mice in the formation of the glucuronide conjugate of PA and in the formation of 2-propynoic acid and metabolites derived from glutathione. These metabolites represent further variation on glutathione metabolism following its addition to the carbon-carbon triple bond compared to those described for the rat.

Alkynes↗
PubMed2000

Stilbene glycoside sulfates from Polygonum cuspidatum.

Ten naturally occurring stilbene glycoside sulfates (1-10) were isolated from an aqueous extract of the root of Polygonum cuspidatum. Their structures were established based on chemical evidence and spectroscopic techniques, including 2D NMR methods.

Magnetic Resonance Spectroscopy↗
PubMed2000

Three-dimensional structure of nucleoside diphosphate kinase.

Three-dimensional structures are known from X-ray studies of the nucleoside diphosphate (NDP) kinase of many organisms from bacteria to human. All NDP kinases have subunits of about 150 residues with a very similar fold based on the alphabeta sandwich or ferredoxin fold. This fold is found in many nucleotide or polynucleotide-binding proteins with no sequence relationship to NDP kinase. This common fold is augmented here with specific features: a surface alpha-helix hairpin, the Kpn loop, and the C-terminal extension. The alpha-helix hairpin and Kpn loop make up the nucleotide binding site, which is unique to NDP kinase and different from that of other kinases or ATPases. The Kpn loop and the C-terminal extension are also involved in the quaternary structure. Whereas all known eukaryotic NDP kinases, including mitochondral enzymes, are hexamers, some bacterial enzymes are tetramers. However, hexameric and tetrameric NDP kinases are built from the same dimer. The structural environment of the active histidine is identical in all. The nucleotide binding site is also fully conserved, except for a feature implicating C-terminal residues in the hexamer, but not in the tetramer. Structural data on the native and phosphorylated enzyme, complexes with substrates, inhibitor, and a transition state analog, give a solid basis to a mechanism of phosphate transfer in which the largest contributors to catalysis are the 3'-OH of the sugar and the bound Mg2+ in the nucleotide substrate. In contrast, we still lack structural data relating to DNA binding and other functions of NDP kinases.

Animals↗
PubMed2000

Left ventricular tachycardia originating near the left main coronary artery.

Eight patients with idiopathic ventricular tachycardia (VT) underwent mapping and radiofrequency ablation. Mapping showed VT originating in the high posterolateral left ventricular outflow tract in proximity to the left main and proximal circumflex coronary arteries. Ablation was not attempted due to this proximity to the left main and proximal circumflex coronary arteries. Ablation was not attempted due to this proximity in 2 patients and limited in 1 patient. It was successful in VT suppression in 5 of 6 patients.

Adult↗
PubMed2000

Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1.

Sphingosylphosphorylcholine (SPC) is a bioactive lipid that acts as an intracellular and extracellular signalling molecule in numerous biological processes. Many of the cellular actions of SPC are believed to be mediated by the activation of unidentified G-protein-coupled receptors. Here we show that SPC is a high-affinity ligand for an orphan receptor, ovarian cancer G-protein-coupled receptor 1 (OGR1). In OGR1-transfected cells, SPC binds to OGR1 with high affinity (Kd = 33.3 nM) and high specificity and transiently increases intracellular calcium. The specific binding of SPC to OGR1 also activates p42/44 mitogen-activated protein kinases (MAP kinases) and inhibits cell proliferation. In addition, SPC causes internalization of OGR1 in a structurally specific manner.

Calcium↗
PubMed2000

C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge.

The ability of the C3d component of complement to enhance antibody responses and protective immunity to influenza virus challenges was evaluated using a DNA vaccine encoding a C3d fusion of the hemagglutinin (HA) from influenza virus. Plasmids were generated that encoded a transmembrane HA (tmHA), a secreted form of HA (sHA), or a sHA fused to three tandem copies of the murine homologue of the C3d (sHA-3C3d). Analysis of the titers, avidity maturation, and hemagglutinin-inhibition activity of raised antibody revealed that immunizations with sHA-3C3d DNA accelerated both the avidity maturation of antibody to HA and the appearance of hemagglutinin-inhibition activity. These accelerated antibody responses correlated to a more rapid appearance of protective immunity. They also correlated to complete protection from live virus challenge by a single vaccination at a dose ten times lower than the protective dose for non-C3d forms of HA.

Animals↗