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Biomedical subjects

J Lu

Publications and source records attributed to J Lu.

At least 19 recordsLinked to original sources
PubMed2004

Diode-end-pumped 4.2-W continuous-wave Yb:Y2O3 ceramic laser.

We report on an efficient diode-end-pumped polycrystalline Yb:Y2O3 ceramic laser. Continuous-wave output power of 4.2 W at 1078 nm was obtained under pump power of 19.5 W. The corresponding slope efficiency was 29%. The beam quality factor (M2) at full pump power was measured to be 1.63. The threshold wavelengths of the laser at various output couplings were also investigated. It was found that the threshold wavelengths shifted approximately 5 nm when the reflectivity of the output coupler changed from 90% to 99.9%, as caused by the strong reabsorption effect in the ceramic sample.

Journal Article↗
PubMed2004

Role of phenytoin in wound healing: microarray analysis of early transcriptional responses in human dermal fibroblasts.

Wound healing is a complex process involving a number of related genes and receptors. Using cDNA microarrays, we explored the global gene expression profile of phenytoin (20microg/ml) induced changes to human dermal fibroblasts. Microarray data analysis revealed approximately 1500 genes were differentially expressed by 2.5-fold. At 3, 6, 12, and 24h, the transcripts of the major growth factors involved in wound healing and their receptors were increased. This was further confirmed by RT-PCR. Genes encoding other proteins with roles in signal transduction (NFkappaB), extracellular matrix (MMP1) including type I collagen, fibronectin, and laminin were strongly induced at 6h and onwards. Genes involved in cell cycle regulation (CCND1 and CDKN1A) were down-regulated consistent with our finding that phenytoin per se did not have cell proliferation activity. Notably, phenytoin accelerates the autocrine and paracrine activity of growth factors by up-regulating the related receptors.

Cell Cycle↗
PubMed2004

Flavor decomposition of the sea-quark helicity distributions in the nucleon from semiinclusive deep inelastic scattering.

Double-spin asymmetries of semiinclusive cross sections for the production of identified pions and kaons have been measured in deep inelastic scattering of polarized positrons on a polarized deuterium target. Five helicity distributions including those for three sea quark flavors were extracted from these data together with reanalyzed previous data for identified pions from a hydrogen target. These distributions are consistent with zero for all three sea flavors. A recently predicted flavor asymmetry in the polarization of the light quark sea appears to be disfavored by the data.

Journal Article↗
PubMed2004

Random-wavelength solid-state laser.

The spectral properties of a diode-pumped Yb:Y2O3 ceramic laser are reported. We show experimentally that the instantaneous emission wavelengths of the laser change randomly with time, whereas its emission has fixed well-defined transverse modes. The central wavelength of the laser emission also shifts prominently with the increase of intracavity light intensity. It is found that the spectral properties of the laser can be explained well based on the strong reabsorption of light in the gain medium.

Journal Article↗
PubMed2004

Spermine reduces infarction and neurological deficit following a rat model of middle cerebral artery occlusion: a magnetic resonance imaging study.

The role of nitric oxide (NO) in post-ischemic cerebral infarction has been extensively examined, but few studies have investigated its role on the neurological deficit. In the present study, we investigated the effect of spermine on the temporal evolution of infarct volume, NO production and neurological deficit using magnetic resonance imaging in a model of permanent focal cerebral ischemia in rats. Spermine given at 10 mg/kg 2 h after ischemia reduced the infarct volume by 40% and abolished brain NO production and improved the neurological score 24 h, 48 h and 72 h after ischemia. Spermine also reduced the neurological deficit as evaluated by rotamex, grip strength and neurological severity score tests.

Analysis of Variance↗
PubMed2004

Endothelial progenitor cells' "homing" specificity to brain tumors.

Current treatment of malignant glioma brain tumors is unsatisfactory. Gene therapy has much promise, but target-specific vectors are needed. Endothelial progenitor cells (EPCs) have in vivo homing specificity to angiogenic sites and are thus potential vehicles for site-specific gene therapy. However, reports of EPCs "homing" to intracranial solid tumors are lacking. We investigated EPCs' "homing" specificity using a murine intracranial glioma model. EPCs, derived from human cord blood, were labeled with a fluorogenic agent CFSE and intravenously injected into SCID mice bearing orthotopic gliomas. At 7-14 days after EPC injection, mouse brains and other vital organs were examined for distribution of transplanted EPCs. As controls, CFSE-labeled human umbilical vein endothelial cells (HUVECs) and EPCs were intravenously injected into matched glioma SCID mice (HUVEC control groups) and nontumor SCID mice (nontumor-bearing control groups), respectively. Fluorescence image analysis revealed that systemically transplanted EPCs 'homed' to brain tumors with significantly higher specificity as compared to other organs within the experimental group (P<0.001) and to anatomically matched brain sections from the control groups (P<0.001). Our study demonstrates EPCs' in vivo tropism for intracranial gliomas, with potential for cell delivery of brain tumor spatial-specific gene therapy.

Animals↗
PubMed2004

Homology modeling of lanosterol 14alpha-demethylase of Candida albicans and Aspergillus fumigatus and insights into the enzyme-substrate Interactions.

The crystal structure of 14alpha-sterol demethylase from Mycobacterium tuberculosis (MT_14DM) provides a good template for modeling the three dimensional structure of lanosterol 14alpha-demethylase, which is the target of azole antifungal agents. Homologous 3D models of lanosterol 14alpha-demethylase from Candida albicans (CA_14DM) and Aspergillus fumigatus (AF_14DM) were built on the basis of the crystal coordinates of MT_14DM in complex with 4-phenylimidazole and fluconazole. The reliability of the two models was assessed by Ramachandran plots, Profile-3D analysis, and by analyzing the consistency of the two models with the experimental data on the P450(14DM). The overall structures of the resulting CA_14DM model and AF_14DM model are similar to those of the template structures. The two models remain the core structure characteristic for cytochrome P450s and most of the insertions and deletions expose the molecular surface. The structurally and functionally important residues such as the heme binding residues, the residues lining the substrate access channel, and residues in active site were identified from the model. To explore the binding mode of the substrate with the two models, 24(28)-methylene-24,25-dihydrolanosterol was docked into the active site of the two models and hydrophobic interaction and hydrogen-bonding were found to play an important role in substrate recognition and orientation. These results provided a basis for experiments to probe structure-function relationships in the P450(14DM). Although CA_14DM and AF_14DM shared similar core structural character, the active site of the two models were quite different, thus allowing the rational design of specific inhibitors to the target enzyme and the discovery of novel antifungal agents with broad spectrum.

Amino Acid Sequence↗
PubMed2004

A vertebral dislocation model of spinal cord injury in rats.

A new model of spinal cord injury (SCI) has been developed in the rat, which produces axonal and vascular injury within the spinal cord through lateral displacement of the vertebral column. An electromechanical feedback-controlled device produces the injury by displacing the vertebral column to the left hand side. The speed and lateral displacement is controllable by the user, and the resulting injury ranges from no histologically evident injury, to total disruption of the vertebral column with associated widespread axonal and vascular damage. Histological and immunohistological techniques were employed to correlate mechanical parameters with the extent of pathological injury of spinal cord. Axonal injury was most severe in the left lateral white matter, and vascular injury was concentrated in the gray matter.

Animals↗
PubMed2003

Effects of contralateral sound stimulation on unit activity of ventral cochlear nucleus neurons.

The cochlear nucleus (CN) commissural connection represents the first opportunity for convergence of binaural information in the auditory brainstem. All major neuron types in the ventral CN (VCN) are innervated by a diverse population of cells in the contralateral VCN. This study examined the effect of contralateral sound stimulation on the spontaneous rates (SRs) of neurons in the VCN. Unit activity was recorded with silicon-substrate multichannel probes which allowed recordings from up to 16 sites simultaneously. On average, 30% of units showed short-latency (often only 2 ms greater than the latencies of ipsilateral sound-evoked responses) inhibition of SR by wideband contralateral noise bursts. Fewer units (4.5%) were excited by contralateral noise at sound levels low enough to exclude excitation by acoustic crossover. Both regular and irregular units in the anterior VCN (AVCN) and posterior VCN (PVCN) were inhibited by contralateral sound. Decrements in SR followed a monotonic function with increases in contralateral sound level, except where responses could be attributed to acoustic crossover. Restricting the contralateral noise bandwidth resulted in a frequency-specific inhibition, dominated by frequencies at and below the ipsilateral BF of the unit, consistent with anatomical findings of the tonotopic organization of the CN commissural pathway. The latencies of these effects are compatible with mono, di and tri-synaptic connections reflecting CN commissural pathway effects.

Acoustic Stimulation↗
PubMed2003

A rapid screen for functional mutants of TraM, an autoregulatory protein required for F conjugation.

TraM is an autoregulatory protein required for conjugative transfer of the F plasmid. A rapid screening procedure was developed to select for traM mutants constructed by random PCR mutagenesis. The mutated traM gene was cloned into pT7-5, without the traM promoters (collectively called P( traM)), such that these mutants were expressed from the downstream traJ promoter, resulting in constitutive, low-level, transcription of traM by polymerases that had circumnavigated the plasmid. P( traM) was cloned into pPR9tt as a translational fusion in which a DNA fragment containing P( traM), the ribosome binding site and first 24 codons of traM was fused to the 5' end of lacZ. To downregulate beta-galactosidase expression, a -1 frameshift mutation was introduced at the junction between traM and lacZ in the fusion. Selected TraM mutants were further characterized for their intracellular levels, electrophoretic mobility on nondenaturing gels, and activity in F conjugation. Point mutations throughout TraM were found to affect both autoregulation and conjugative function.

Bacterial Proteins↗
PubMed2003

Nitriding iron at lower temperatures.

The microstructure in the surface layer of a pure iron plate was refined at the nanometer scale by means of a surface mechanical attrition treatment that generates repetitive severe plastic deformation of the surface layer. The subsequent nitriding kinetics of the treated iron with the nanostructured surface layer were greatly enhanced, so that the nitriding temperature could be as low as 300 degrees C, which is much lower than conventional nitriding temperatures (above 500 degrees C). This enhanced processing method demonstrates the technological significance of nanomaterials in improving traditional processing techniques and provides a new approach for selective surface reactions in solids.

Journal Article↗
PubMed2003

Effects of trigeminal ganglion stimulation on unit activity of ventral cochlear nucleus neurons.

The trigeminal ganglion sends a projection to the granule and magnocellular regions of the ventral cochlear nucleus (VCN; [J Comp Neurol 419 (2000) 271]), as well as to the cochlea ([Neuroscience 79 (1997) 605; Neuroscience 84 (1998a) 559]). We investigated the effects of electrically stimulating the trigeminal ganglion on unit responses in the guinea-pig VCN. Responses consisted of one, two or more phases of excitation, sometimes followed by a longer inhibitory phase. The latencies to the first excitation peak ranged between 5 and 17 ms from the onset of stimulation. These responses were preceded by a slow wave potential evoked by the stimulation. Applying kainic acid, which eliminates VIIIth nerve responses, diminished the firing rates of VCN units to trigeminal stimulation, and increased their first spike latencies. Cochlear destruction had a similar effect. The responses in VCN evoked by trigeminal ganglion stimulation therefore appear to result from direct stimulation of the trigeminal ganglion-cochlear nucleus pathway, as well as modulation by the trigeminal ganglion-cochlear pathway. Alternatively, a reduction in spontaneous rate of VCN neurons by removal of VIIIth nerve input could explain the decreased response to trigeminal stimulation after cochlear manipulations. The modulation of firing rate in second order auditory neurons by first order somatosensory neurons could influence central auditory targets and may be involved in generating or modulating perceptions of phantom sounds which can be modified by manipulations of somatic regions of the head and neck ("somatic tinnitus").

Action Potentials↗
PubMed2003

Ionotropic and metabotropic glutamate receptor mediation of glucocorticoid-induced apoptosis in hippocampal cells and the neuroprotective role of synaptic N-methyl-D-aspartate receptors.

Glutamate receptors have been proposed to mediate the apoptotic actions of glucocorticoids in hippocampal cells. To further analyze the role of glutamate receptors in this process, we pretreated primary hippocampal cells from neonatal (postnatal day 4) rats with antagonists of ionotropic glutamate receptor (iGluR) and metabotropic glutamate receptor (mGluR) antagonists before exposure to the specific glucocorticoid receptor agonist dexamethasone (DEX) at a dose of 1 microM. Dizocilpine (MK801; a general N-methyl-D-aspartic acid [NMDA] receptor antagonist, NMDAR antagonist) and ifenprodil (a specific ligand of the NMDAR 2B subunit, NR2B), were used to block iGluR; (RS)-alpha-ethyl-4-carboxyphenylglycine (E4CPG) and (RS)-alpha-cyclopropyl-4-phosphonophenyl-glycine (CPPG) were employed as I/II (E4CPG) and II/III (CPPG) mGluR antagonists. Blockade of iGluR resulted in a significant attenuation of DEX-induced cell death; the finding that ifenprodil exerted a similar potency to MK801 demonstrates the involvement of NR2B receptors in glucocorticoid-induced cell death. Apoptosis accounted for a significant amount of the cell loss observed, as detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling histochemistry for the in situ labeling of DNA breaks; apoptotic cells were distinguished from necrosis on the basis of morphological criteria, including chromatin condensation, membrane blebbing and presence of apoptotic bodies. Treatment with E4CPG and CPPG completely abolished the apoptotic response to DEX, thus showing the additional contribution of mGluR to the phenomenon. Further, dose-response studies with NMDA revealed that whereas high (10 microM) doses of NMDA themselves elicit cytotoxic responses, low (1-5 microM) concentrations of NMDA can effectively oppose DEX-induced cell death. Interestingly, the neuroprotective actions of low dose NMDA stimulation were abolished when either synaptic or extrasynaptic NMDA receptors were blocked with MK801 in combination with the GABA receptor antagonist bicuculline (synaptic) or ifenprodil (extrasynaptic). In summary, the present data show that both iGluR and mGluR mediate the neurotoxic effects of glucocorticoids on hippocampal cells and that pre-treatment with low doses of NMDA, by acting on synaptic and extrasynaptic receptors, render hippocampal cells less vulnerable to glucocorticoid insults.

Animals↗
PubMed2003

Specificity and functional characteristics of anti-HLA-A mAbs LGIII-147.4.1 and LGIII-220.6.2.

Only three anti-HLA-A monoclonal antibodies (mAbs) have been described in the literature. Two of them recognize determinants shared by only a few HLA-A allospecificities. The third one, mAb 3G11, recognizes a determinant shared by most HLA-A allospecificities. Being an IgM, the latter mAb is not likely to be a useful probe in immunohistochemical reactions and in functional assays. Therefore, in the present study we have characterized the specificity of the mAbs LGIII-147.4.1 and LGIII-220.6.2. The two mAbs that do not share idiotypic determinants recognize distinct but spatially close antigenic determinants expressed on most of the gene products of the HLA-A locus. Specifically, the determinant recognized by mAb LGIII-220.6.2 is expressed on HLA-A1, -A2, -A3, -A26, -A28, -A29, -A30, -A33, -A36, -A74 and -A80 allospecificities. The determinant recognized by mAb LGIII-147.4.1, which appears to be located on the amino-acid residues 79-83 of the heavy chain, is expressed on all HLA-A allospecificities but HLA-A23, -A24, -A25 and -A32. Because of its broad reactivity, the mAb LGIII-147.4.1 was characterized in a number of assays. It was found to be a useful probe to measure the HLA-A antigen level in serum, to assess the HLA-A restriction of cytotoxic T lymphocytes (CTL) and to monitor HLA-A antigen expression in normal and malignant lesions.

Animals↗
PubMed2003

Gamma-MSH peptides in the pituitary: effects, target cells, and receptors.

The melanocortin (MC) gamma3-MSH is believed to signal through the MC3 receptor. We showed that it induces a sustained increase in intracellular free calcium levels ([Ca(2+)](i)) in a subpopulation of pituitary cells. Most of the cells responding to gamma3-MSH express more than one pituitary hormone mRNA. The effect of gamma3-MSH is blocked by SHU9119, a MC3R and MC4R antagonist, in only 50% of the responsive cells, suggesting that in half of these cells the mediating receptor is not the MC3R. Low picomolar doses of gamma3-MSH increase [Ca(2+)](i) in the growth hormone (GH)- and prolactin (PRL)-secreting GH3 cell line. gamma2-MSH and alpha-MSH display a similar effect. SHU9119 does not affect the gamma3-MSH-induced [Ca(2+)](i) response. MTII, a potent synthetic agonist of the MC3R, MC4R, and MC5R, also shows no or low potency in increasing [Ca(2+)](i). By means of RT-PCR, the mRNA of the MC2R, MC3R, and MC4R receptors is undetectable. Experiments testing gamma2-MSH analogues with single alanine replacements show that, unlike the classic MCRs, the His(5)-Phe(6)-Arg(7)-Trp(8) sequence in gamma2-MSH is not a core sequence for activating the gamma-MSH receptor in GH3 cells, whereas Met(3) is essential. Low nanomolar doses of gamma-MSH increase intracellular cAMP levels. Blockade of protein kinase A abolishes the [Ca(2+)](i) responses to gamma3-MSH. gamma2-MSH increases binding of [S(35)]GTPgammaS to membrane preparations of GH3 cells. The pharmacological characteristics of gamma-MSH peptides and analogues on [Ca(2+)](i) and the signal-transduction pathways present strong evidence for the expression of a hitherto uncharacterized gamma-MSH receptor in GH3 cells, belonging to the G protein-coupled receptor family.

Amino Acid Sequence↗
PubMed2002

MoeA, an enzyme in the molybdopterin synthesis pathway, is required for rifamycin SV production in Amycolatopsis mediterranei U32.

Rifamycin SV contains one amide nitrogen atom at its C(7)N moiety. Earlier labeling studies suggested that nitrogen might be incorporated from a pathway involved in a molybdenum-dependent nitrate reductase. However, no genetic evidence is available thus far. The structural gene moeA, which is involved in molybdopterin synthesis in various organisms, has been cloned from rifamycin SV-producing Amycolatopsis mediterranei strain U32. The amino acid sequence deduced from the moeA gene showed significant similarity to members of the MoeA protein family and contains all the structural features that are highly conserved in the putative functional domains of MoeA proteins. Southern hybridization showed that there is only one moeA gene in the A. mediterranei genome. To further investigate the possible physiological function of the moeA gene, a double crossover gene replacement was achieved by inserting an aparmycin resistance gene into moeA in the A. mediterranei U32 chromosome. Phenotype analysis showed that the moeA gene is required for A. mediterranei growth in a minimal medium with nitrate as sole nitrogen source, possibly because nitrate reductase activity is diminished due to disruption of the moeA gene. Compared to the wild type strain, moeA-disrupted mutants lost 95% of their rifamycin SV production capacity in complex fermentation media. The results demonstrate that the moeA gene is necessary for rifamycin SV production in A. mediterranei, and that the nitrogen assimilation pathway involved in nitrate reductase is the major pathway for the genesis of the amide nitrogen atom in the rifamycin SV molecule.

Actinomycetales↗