Biomedical subjects

Lijing Xu

Publications and source records attributed to Lijing Xu.

6 recordsLinked to original sources

PubMed2006

Murine central and peripheral nervous system transcriptomes: comparative gene expression.

The central and peripheral nervous systems exhibit significant embryological, morphological, and functional differences. Moreover, the pathology of most acquired and hereditary neurological diseases preferentially targets specific components of the nervous system. In order to test the hypothesis that central and peripheral neural transcriptomes show fundamental quantitative differences, Affymetrix GeneChip expression arrays were used to compare murine lumbar spinal cord (SC) and dorsal root ganglion (DRG) gene expression. As the crucial component of a novel technique to preserve RNA integrity, mice were perfusion-fixed with RNAlater before the SC and DRG were harvested. As per Affymetrix terminology, a total of 111 transcripts were present (P) on all DRG arrays, absent (A) on all SC arrays, and demonstrated at least 10-fold greater expression in DRG than in SC. Conversely, a total of 112 transcripts were present on all SC arrays, absent on all DRG arrays, and showed at least 10-fold greater expression in SC than in DRG. For a subset of transcripts, quantitative real-time RT-PCR was used to corroborate and validate microarray results. Among those genes enriched in DRG, many belonged to a few distinct functional classes: G-protein coupled receptor-protein signaling pathways, potassium transport, sodium transport, sensory perception, and cell-surface receptor-linked signal transduction. In contrast, genes associated with synaptic transmission, organic acid transport, neurotransmitter transport, and circulation were enriched in SC. Notably, the majority of genes causally associated with hereditary neuropathies were highly enriched in DRG. These differential neural gene expression profiles provide a robust framework for future molecular and genetic studies of neuropathy and SC diseases.

Animals↗

PubMed2006

The effect of monaural middle ear destruction on response properties of neurons in the auditory midbrain of juvenile and adult mice.

This article reviews our studies of the effect of monaural middle ear destruction on midbrain auditory response properties of the laboratory mouse, Mus musculus. Monaural middle ear destruction was performed on juvenile and adult mice and the auditory sensitivity of neurons in the midbrain inferior colliculus (IC) ipsilateral and contralateral to the intact ear was examined 4 weeks later. When stimulated with sound pulses, IC neurons of the control mice typically had lower minimum threshold, larger dynamic range, and sharper frequency tuning curve than IC neurons of the experimental juvenile and adult mice. In the experimental mice, neurons in the ipsilateral IC had significantly longer latency, higher minimum threshold, and smaller dynamic range than neurons in the contralateral IC. When determined at two sound directions (ipsilateral 40 degrees and contralateral 40 degrees to the recording site), IC neurons of the control mice had higher minimum threshold, sharper frequency tuning curve but smaller dynamic range at I-40 degrees than at C-40 degrees . However, these direction-dependent response properties were not observed for IC neurons of the experimental juvenile and adult mice. Clear tonotopic organization was only observed in the IC of the control mice and experimental adult mice but not in the IC of experimental juvenile mice. These different response properties are discussed in relation to the effect of monaural middle ear destruction.

Acoustic Stimulation↗

PubMed2004

The development of potent non-peptidic PTP-1B inhibitors.

The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM).

Administration, Oral↗

PubMed2002

Discovery of a potent and selective COX-2 inhibitor in the alkoxy lactone series with optimized metabolic profile.

The COX-2 inhibitor DFP [5,5-dimethyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanone] was found to have a long half-life in humans. Analogues have been characterized in order to optimize pharmacokinetics. This has lead to the discovery of 5(S)-(5-ethyl-5-methyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanone analogue 11 a potent and selective COX-2 inhibitor which is metabolized to a greater extent than DFP upon incubation with rat and human hepatocytes, suggesting a shorter half-life in humans.

Animals↗

PubMed2002

Monaural middle ear destruction in juvenile and adult mice: effects on responses to sound direction in the inferior colliculus ipsilateral to the intact ear.

This study examined the effect of monaural middle ear destruction on auditory responses to sound direction in the inferior colliculus (IC) of the laboratory mice, Mus musculus. Monaural middle ear destruction was performed on juvenile and adult mice (the experimental mice). Auditory response properties of neurons to ipsilateral and contralateral sounds (I-40 degrees and C-40 degrees ) were examined in the IC ipsilateral to the intact ear 4 weeks later. IC neurons of control mice had higher minimum thresholds (MTs), larger Q(n) (Q(10), Q(30)) values but smaller dynamic ranges at I-40 degrees than at C-40 degrees. These direction-dependent response properties were not observed for IC neurons of experimental juvenile and adult mice. However, Q(n) values of IC neurons were significantly smaller in experimental juvenile than in control and experimental adult mice. Normal tonotopic organization in terms of positive correlation between recording depth and best frequency (BF) was observed in the IC of control and experimental adult mice at both sound directions but not in the IC of experimental juvenile mice. A positive correlation of increasing MT with BF was only observed for IC neurons in control mice but not in both experimental mice. Possible mechanisms for these different response properties are discussed.

Aging↗

PubMed2002

Multiple comparisons model-based clustering and ternary pattern tree numerical display of gene response to treatment: procedure and application to the preclinical evaluation of chemopreventive agents.

Microarray technology has greatly aided the identification of genes that are expressed differentially. Statistical analysis of such data by multiple comparisons procedures has been slow to develop, in part, because methods to cluster the results of such comparisons in biologically meaningful ways have not been available. We isolated and analyzed, by Northern blot and GeneChip, replicate liver RNA samples (n = 4/group) from rats fed with control diet or diet containing one of three chemopreventive compounds, selected because their pharmacological activities, including RNA expression response, are relatively well understood. We report on a classification tree, based on the results of nonparametric multiple comparisons, which results in the bipolar hierarchical clustering of genes in relation to their response to treatment. In addition to identifying treatment-responsive genes, application of this procedure to our test study identified the known pharmacological relationships among the treatment groups without supervision. Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds.

Animals↗