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Biomedical subjects

Wei Zhu

Publications and source records attributed to Wei Zhu.

At least 109 records · Page 6Linked to original sources
PubMed2004

Statistical approaches in the analysis of gene expression data derived from bone regeneration specific cDNA microarrays.

Recent advances in molecular biology (e.g., cDNA microarray technology) enables the simultaneous monitoring of the expression level of thousands of genes. Due to the massive amount of complex data generated, sophisticated statistical approaches are necessary in order to properly address the experimental investigation. In this paper, we present statistical analysis of cDNA microarray data derived from bone regeneration experiments. Several interesting features from these data distinguish it from commonly used microarray experiment (i.e., separate hybridization of mRNA samples from reference and experimental tissues, selectively spotted cDNA sequences and 1060 systematically selected blank spots included in each array). Using this data set, we propose new methods for bioinformatic data normalization, as well as the modification and application of various other published methods in order to identify co-regulated gene expression patterns during the healing of a bone fracture. The proposed normalization methods perform effectively to eliminate the variations with a simple algorithm. Results from our cluster analysis revealed several clusters having distinct gene expression patterns during fracture healing. Our simulation study supports the reliability of the proposed methods.

Adenosylmethionine Decarboxylase↗
PubMed2004

An agonist human ICOS monoclonal antibody that induces T cell activation and inhibits proliferation of a myeloma cell line.

The inducible costimulator (ICOS), the third member of the CD28/CD152 receptor family, is an important costimulatory molecule during the immune response. In this study, a functional anti-human ICOS MAb 2C7 was obtained. The specificity of this MAb was verified by flow cytometry, Western blotting, and competition with anti-ICOS MAb ISA3. This MAb could well recognize ICOS molecule expressed on activated T cells and induce the activation as well as proliferation of T cells prestimulated by anti-human CD3 MAb. Furthermore, we found that MAb 2C7 could induce the growth arrest of XG2 cells, a human multiple myeloma cell line, which abnormally expressed ICOS molecule, and led to its apoptosis after 48 h of treatment. This functional anti-human ICOS MAb provides a valuable tool for further study of biological functions as well as signal transduction of ICOS/GL50.

Animals↗
PubMed2004

Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence.

OBJECTIVE: Methamphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. The authors recently reported that decreases in dopamine transporters (used as markers of dopamine terminals) in the striatum of methamphetamine abusers recover with protracted abstinence and that relative to comparison subjects, recently detoxified methamphetamine abusers have lower metabolism in the striatum and thalamus. In this study, the authors assessed whether metabolism recovers with protracted abstinence. METHOD: Brain glucose metabolism was measured with positron emission tomography and [18F]fluorodeoxyglucose in five methamphetamine abusers who were evaluated after both a short (<6 months) and protracted (12-17 months) abstinence interval, eight methamphetamine abusers tested only after protracted abstinence, and 11 comparison subjects who were not drug users. RESULTS: Significantly greater thalamic, but not striatal, metabolism was seen following protracted abstinence relative to metabolism assessed after a short abstinence interval, and this increase was associated with improved performance in motor and verbal memory tests. Relative to the comparison subjects, the methamphetamine abusers tested after protracted abstinence had lower metabolism in the striatum (most accentuated in the caudate and nucleus accumbens) but not in the thalamus. CONCLUSIONS: The persistent decreases in striatal metabolism in methamphetamine abusers could reflect long-lasting changes in dopamine cell activity, and decreases in the nucleus accumbens could account for the persistence of amotivation and anhedonia in detoxified methamphetamine abusers. The recovery of thalamic metabolism could reflect adaptation responses to compensate for the dopamine deficits, and the associated improvement in neuropsychological performance further indicates its functional significance. These results suggest that while protracted abstinence may reverse some of the methamphetamine-induced alterations in brain function, other deficits persist.

Adaptation, Physiological↗
PubMed2004

Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain.

OBJECTIVE: Methylphenidate is the most commonly prescribed drug for attention deficit hyperactivity disorder (ADHD), yet its therapeutic mechanisms are poorly understood. The objective of this study was to assess if methylphenidate, by increasing dopamine (neurotransmitter involved in motivation) in brain, would enhance the saliency of an academic task, making it more interesting. METHOD: Healthy subjects (N=16) underwent positron emission tomography with [(11)C]raclopride (dopamine D(2) receptor radioligand that competes with endogenous dopamine for binding) to assess the effects of oral methylphenidate (20 mg) on extracellular dopamine in the striatum. The authors compared the effects of methylphenidate during an academic task (solving mathematical problems with monetary reinforcement) and a neutral task (passively viewing cards with no remuneration). In parallel, the effects of methylphenidate on the interest that the academic task elicited were also evaluated. RESULTS: Methylphenidate, when coupled with the mathematical task, significantly increased extracellular dopamine, but this did not occur when coupled with the neutral task. The mathematical task did not increase dopamine when coupled with placebo. Subjective reports about interest and motivation in the mathematical task were greater with methylphenidate than with placebo and were associated with dopamine increases. CONCLUSIONS: The significant association between methylphenidate-induced dopamine increases and the interest and motivation for the task confirms the prediction that methylphenidate enhances the saliency of an event by increasing dopamine. The enhanced interest for the task could increase attention and improve performance and could be one of the mechanisms underlying methylphenidate's therapeutic effects. These findings support educational strategies that make schoolwork more interesting as nonpharmacological interventions to treat ADHD.

Adult↗
PubMed2004

Mesenchymal stem cells from adult human bone marrow differentiate into a cardiomyocyte phenotype in vitro.

A method for isolating adult human bone marrow mesenchymal stem cells (MSCs) was established, and the ability of human MSCs to differentiate into cells with characteristics of cardiomyocytes in vitro was investigated. Selected MSC surface antigens were analyzed by flow cytometry. The MSCs at Passage 2 were treated with 5-azacytidine to investigate their differentiation into cardiomyocytes. Characteristics of the putative myogenic cells were determined by immunohistochemistry and transmission electron and confocal microscopies. The expression of myogenic specific genes was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and DNA sequencing. The MSCs were spindle-shaped with irregular processes and were respectively positive for CD(13), CD(29), CD(44), CD(71) and negative for CD(3), CD(14), CD(15), CD(33), CD(34), CD(38), CD(45), and HLA-DR. The myogenic cells differentiated from MSCs were positive for beta-myosin heavy chain (beta-MHC), desmin, and alpha-cardiac actin. When the myogenic cells were stimulated with low concentration of K(+) (5.0 mM), an increase in intracellular calcium fluorescence was observed. Myofilament-like structures were observed in electron micrographs of the differentiated myogenic cells. The mRNAs of beta-MHC, desmin, alpha-cardiac actin, and cardiac troponin T were highly expressed in the myogenic cells. These results indicate that 5-azacytidine can induce human MSCs to differentiate in vitro into cells with characteristics commonly attributed to cardiomyocytes. Cardiomyocytes cultured from bone marrow sources are potentially valuable for repairing injured myocardium.

Actins↗
PubMed2004

Opiate alkaloids and nitric oxide production in the nematode Ascaris suum.

The tissue distribution, course of secretion, and sex differences of morphine were delineated in Ascaris suum. Nitric oxide (NO) release in various tissues in response to morphine and its metabolite morphine-6-glucuronide (M6G) were also examined. Ascaris suum of both sexes along with their incubation fluid were analyzed for morphine concentrations by high-performance liquid chromatography (HPLC) over a 5-day period. Various tissues were also dissected for HPLC and NO analysis. Morphine was found to be most prevalent in the muscle tissue, and there is significantly more morphine in females than males, probably because of the large amounts present in the female uterus. Morphine (10(-9) M) and M6G (10(-9) M) stimulated the release of NO from muscles. Naloxone (10(-7) M) and N-nitro-L-arginine methyl ester (10(-6) M) blocked (P < 0.005) morphine-stimulated NO release from A. suum muscle tissue. D-Phe-Cys-Tyr-D-Trp-Om-Thr-Pen-Thr-NH2 (CTOP) (10(-7) M) did not block morphine's NO release. However, naloxone could not block M6G-stimulated NO release by muscles, whereas CTOP (10(-7) M) blocked its release. These findings were in seeming contradiction to our earlier inability to isolate a mu opiate receptor messenger RNA by reverse transcriptase-polymerase chain reaction using a human mu primer. This suggests that a novel mu opiate receptor was possibly present and selective toward M6G.

Animals↗
PubMed2004

Nitric oxide modulates microglial activation.

BACKGROUND: Nitric oxide (NO) has important physiological regulatory roles, i.e, vasodilation, neurotransmitter release, etc. Little is known about the processes in neural tissues, which stabilize microglia. This study attempts to answer this question by demonstrating a role for basal NO in maintaining microglia juxtaposed to neurons. MATERIAL/METHODS: Mytilus edulis (a marine bivalve), were used to examine microglia egress from excised pedal ganglia microscopically. Nitric oxide is measured in excised pedal ganglia amperometrically in real-time. RESULTS: Pedal ganglia exhibit basal NO release (1 nM range). Inhibition of basal NO release by L-NAME results in greater numbers of microglia in the incubation medium. This process appears to involve two phases of egress. The first involves a slow egress of microglia, whereas the second, occurring 18 hours later, involves a more rapid release of these cells. Low levels of the NO donor SNAP (1 nM) does not interrupt microglial egress, whereas in the presence of L-NAME it does. Exposing the ganglia to high NO levels for a short period of time inhibits their egress. CONCLUSIONS: Spontaneous ganglionic NO release maintains/stabilizes microglia juxtaposed to neurons. Excised ganglia at the various observation periods reveals a transition of constitutive nitric oxide synthase (NOS) to inducible NOS derived NO. It also appears that the microglia in some unknown manner become insensitive to iNOS derived NO since they exhibit enhanced migration during this last phase of the ganglionic NO response. Taken together, NO is involved with regulating microglial activation.

Animals↗
PubMed2004

[Study on antitumor activities of ginkgolic acids from Ginkgo sarcotestas in vitro].

OBJECTIVE: To study the influence of ginkgolic acids on human tumor cells and normal cells. METHODS: Ginkgolic acids (total concentration 90%) was prepared from ginkgo sarcotestas. The inhibitive effect of ginkgolic acids on human tumor cells and normal cells lines was examined by MTT assay. RESULTS: When the concentration was 5.0 micrograms/ml, ginkgolic acids obviously inhibited the growth of tumor cells and didn't influence the normal cells. Inhibitive rate of ginkgolic acids on LTEP-a-2 was 59.1%. High-concentration ginkgolic acids had inhibitive effect on the growth of tumor cells and normal cells. CONCLUSION: Ginkgolic acids had a obvious inhibitive effect on tumor cells in vitro. When the concentration was under 5.0 micrograms/ml, ginkgolic acids didn't influence the growth of normal cells.

Animals↗
PubMed2004

A novel tumor cell line cloned from mutated human embryonic bone marrow mesenchymal stem cells.

A novel tumor cell line, denominated F6, was established from mutated human embryonic bone marrow mesenchymal stem cells (MSCs) which were induced by the GM-CSF and IL-4 in vitro. The characteristics of the F6 cell line, such as surface antigens, cell cycle, growth curve, gene expression, morphology, cytogenetics and tumor model were analyzed. The F6 cells were round and grew suspended in a plastic dish. The cell line has a strong self-renewal capability, was positive for CD13, CD29, CD44, but negative for CD1alpha, CD3, CD10, CD14, CD23, CD33, CD34, CD38, CD41, CD45, CD54 and HLA-DR. The surface antigens were lower than those of human embryonic MSCs. The karyotype of F6 cells was abnormal. The cell cycle included: G0/G1 phase, 52.24%; G2/M phase, 8.00%; S phase, 41.76%. After the cells had been passaged serially for more than 17 months (62 passages), their characteristics were still retained. The F6 cells resulted in tumors in SCID nude mice in vivo (8/8) and caused metastasis (3/8). The pathologic examination revealed that the tumor cells extensively invaded surrounding normal tissues such as dermis, muscular tissue, nerve tissue, adipose tissue and lymphoid tissue. F6 cell line, tumor tissues derived from F6 cells and the MSCs expressed different levels of the nucleostemin gene. These findings suggested that F6 may be a novel tumor cell line. It may provide evidence for the theory that cancer originates from stem cells, and may be useful for the investigation on safety of human MSCs in the clinical application.

Animals↗
PubMed2004

Nitric oxide as a possible mechanism for understanding the therapeutic effects of osteopathic manipulative medicine (Review).

Throughout the history of medicine we have seen the progression of medical therapies from the empirical to the counter-intuitive, with much pressure being placed upon the scientific community to distinguish the two. This exercise has proven the effectiveness of numerous modern therapeutic techniques that have been adapted into modern medicine with remarkable success. While it is certain that many of these techniques yield beneficial results, the mechanisms by which these results are achieved have not been fully realized. In the present report, we consider the case of osteopathic manipulative medicine (OMM), which represents a therapeutic technique developed over a century ago as a means of non-invasive treatment for numerous ailments. Our intention is to use current findings from our laboratory, as well as those of our colleagues in the area of nitric oxide (NO) research to explain the mechanism through which osteopathic manipulations aid the patient. These reports demonstrate that fluidic motions applied to vascular and nerve tissue in a manner comparable to manipulations can cause a remarkable increase in NO concentration within the blood and vasculature. These findings combined with the overwhelming amount of research into the beneficial effects of constitutive NO provide a dynamic theoretical framework to explain the therapeutic effects of OMM.

Animals↗
PubMed2004

Presence of morphine in rat amygdala: evidence for the mu3 opiate receptor subtype via nitric oxide release in limbic structures.

BACKGROUND: We have identified a novel mu opiate receptor, p3, which is expressed in several human tissues, is selective for opiate alkaloids, insensitive to opioid peptides, and also is coupled to constitutive nitric oxide release. We, and others, have also demonstrated the presence of opiate alkaloids as endogenous substances in various nerve tissues taken from mammals, man and invertebrates. MATERIAL/METHODS: Morphine isolation and identification was achieved by high pressure liquid chromatography coupled to electrochemical detection. This material was finally identified by nano-electrospray ionization quadruple time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Morphine's ability to release nitric oxide from limbic tissues was determined in real-time via an amperometric probe. RESULTS: We demonstrate the presence of morphine in rat brain amygdala at 12.7 +/- 5.4 ng/g wet tissue. Morphine was able to stimulate the release of nitric oxide from hippocampus and amygdalar tissues in a naloxone and L-NAME sensitive manner. Furthermore, rat chow, incubation medium etc, did not contain morphine, eliminating the possibility of contamination. CONCLUSION: This finding provides evidence that morphine biosynthesis occurs in mammalian neural tissues. It also demonstrates that morphine releases nitric oxide in limbic tissues. Given the limbic system involvement in modulating emotion, including experiences related to pain perception, it appears that morphine is involved with this activity.

Amygdala↗
PubMed2004

Reticuline exposure to invertebrate ganglia increases endogenous morphine levels.

OBJECTIVES: Given the presence of morphine, its metabolites and precursors in mammalian and invertebrate tissues, it became important to determine if exposing tissues to an opiate alkaloid precursor, reticuline, would result in increasing endogenous morphine levels. METHOD: Endogenous morphine levels were determined by high pressure liquid chromatography coupled to electrochemical detection and radioimmunoassay following incubation of Mytilus edulis pedal ganglia with reticuline. Nitric oxide (NO) release was determined in real-time via an amperometric probe. Mu opiate receptor affinity for opiate alkaloid precursors was determined by a receptor displacement assay. RESULTS: Morphine is present in the pedal ganglia of Mytilus edulis (1.43 +/- 0.41 ng/mg +/- SEM ganglionic wet weight). Ganglia incubated with 50 ng of reticuline, a morphine precursor in plants, for 1 hour exhibited a statistical increase in their endogenous morphine levels (6.7 +/- 0.7 ng/mg tissue wet weight; P<0.01). This phenomenon is concentration dependent. The increase in ganglionic morphine levels occurs gradually over the 60 min incubation period, beginning 10 minutes post reticuline addition. We show that reticuline (10(-6) M) does not stimulate ganglionic NO release in a manner resembling that of morphine (10(-6) M), which releases NO seconds after its exposure to the ganglia and lasts for 5 minutes. With reticuline, there is a 3 minute delay, which is followed by an extended release period. Furthermore, in binding displacement experiments both reticuline and salutaridine (another morphine precursor) exhibit no binding affinity for the pedal ganglia mu opiate receptor subtype. This finding is further substantiated using the positive control of human monocytes where the mu3 opiate receptor subtype has been cloned. CONCLUSION: Taken together, we surmise that the morphine's precursors are being converted to morphine. The experiments strongly indicate that pedal ganglia can synthesize morphine from reticuline.

Alkaloids↗
PubMed2004

[Study on anti-bacterium activity of ginkgolic acids and their momomers].

OBJECTIVE: Ginkgolic acids and their three monomers were separated from ginkgo sarcotestas. The anti-bacterium activity of ginkgolic acids were tested. The relation between the anti-bacterium activity and side chain of ginkgolic acid were studied. METHOD: The MIC of ginkgolic acids and their three monomers and salicylic acid were tested. RESULTS: Ginkgolic acid has strong inhibitive effect on G+-bacterium. Salicylic acid has no side chain, so no anti-bacterial activity. When the length of gingkolic acid side chain is C13:0, it has the strongest anti-bacterial activity in three monomers. CONCLUSION: The side chain of ginkgolic acid is the key functional group that possessed anti-bacterial activity. The length of Ginkgolic acid was the main effective factor of anti-bacterial activity.

Anti-Bacterial Agents↗
PubMed2003

Preparation of syn-delta-hydroxy-beta-amino esters via an intramolecular hydrogen bond directed diastereoselective hydrogenation. Total synthesis of (3S,4aS,6R,8S)-hyperaspine.

Hydrogenation of delta-hydroxy-beta-ketoester-derived enamines 8 produces syn-delta-hydroxy-beta-amino esters 9 diastereoselectively, which may be directed by the formation of an intramolecular hydrogen bond between the delta-hydroxyl and beta-amino groups. By using this method and a Dieckmann reaction as the key steps, (3S,4aS,6R,8S)-hyperaspine, a new type of ladybird alkaloid, is synthesized. [reaction: see text]

Animals↗
PubMed2003

Expectation enhances the regional brain metabolic and the reinforcing effects of stimulants in cocaine abusers.

The reinforcing effects of drugs of abuse result from the complex interaction between pharmacological effects and conditioned responses. Here we evaluate how expectation affects the response to the stimulant drug methylphenidate in 25 cocaine abusers. The effects of methylphenidate (0.5 mg/kg, i.v.) on brain glucose metabolism (measured by [18F]deoxyglucose-positron emission tomography) and on its reinforcing effects (self-reports of drug effects) were evaluated in four conditions: (1) expecting placebo and receiving placebo; (2) expecting placebo and receiving methylphenidate; (3) expecting methylphenidate and receiving methylphenidate; (4) expecting methylphenidate and receiving placebo. Methylphenidate increased brain glucose metabolism, and the largest changes were in cerebellum, occipital cortex, and thalamus. The increases in metabolism were approximately 50% larger when methylphenidate was expected than when it was not, and these differences were significant in cerebellum (vermis) and thalamus. In contrast, unexpected methylphenidate induced greater increases in left lateral orbitofrontal cortex than when it was expected. Methylphenidate-induced increases in self-reports of "high" were also approximately 50% greater when subjects expected to receive it than when they did not and were significantly correlated with the metabolic increases in thalamus but not in cerebellum. These findings provide evidence that expectation amplifies the effects of methylphenidate in brain and its reinforcing effects. They also suggest that the thalamus, a region involved with conditioned responses, may mediate the enhancement of the reinforcing effects of methylphenidate by expectation and that the orbitofrontal cortex mediates the response to unexpected reinforcement. The enhanced cerebellar activation with expectation may reflect conditioned responses that are not linked to conscious responses.

Adult↗
PubMed2003

Detection of cancer-specific markers amid massive mass spectral data.

We propose a comprehensive pattern recognition procedure that will achieve best discrimination between two or more sets of subjects with data in the same coordinate system. Applying the procedure to MS data of proteomic analysis of serum from ovarian cancer patients and serum from cancer-free individuals in the Food and Drug Administration/National Cancer Institute Clinical Proteomics Database, we have achieved perfect discrimination (100% sensitivity, 100% specificity) of patients with ovarian cancer, including early-stage disease, from normal controls for two independent sets of data. Our procedure identifies the best subset of proteomic biomarkers for optimal discrimination between the groups and appears to have higher discriminatory power than other methods reported to date. For large-scale screening for diseases of relatively low prevalence such as ovarian cancer, almost perfect specificity and sensitivity of the detection system is critical to avoid unmanageably high numbers of false-positive cases.

Algorithms↗
PubMed2003

Cells previously desensitized to type 1 interferons display different mechanisms of activation of stat-dependent gene expression from naïve cells.

Over the past decade, a wealth of knowledge has been obtained concerning the mechanisms by which interferons (IFNs) and other cytokines activate or down-regulate immediate early genes via the Jak/Stat pathway. In contrast, little information is available on interferon-activated gene expression in naïve cells compared with cells that have been desensitized and subsequently resensitized to the actions of these cytokines. In naïve cells, the ISG54 gene is activated via IFN beta-stimulated formation of ISGF3, a heterotrimeric DNA binding complex consisting of p48 (IRF9) and tyrosine-phosphorylated Stat1 and Stat2. In contrast, in previously desensitized cells IFN beta weakly stimulates the assembly of an ISGF3-like complex that lacks Stat1, even though ISG54 mRNA induction is the same as in naïve cells. The lack of Stat1 tyrosine phosphorylation and DNA binding is due to increased activity of a protein-tyrosine phosphatase. In cells that do not express the tyrosine phosphatase Tc-PTP, the rate of Stat1 dephosphorylation is the same in naïve and previously desensitized cells. These results implicate Tc-PTP in a novel role in the regulation of type 1 interferon-stimulated gene expression.

Animals↗