Biomedical subjects

Liqun Wang

Publications and source records attributed to Liqun Wang.

8 recordsLinked to original sources

PubMed2004

Protection against mucosal simian immunodeficiency virus SIV(mac251) challenge by using replicating adenovirus-SIV multigene vaccine priming and subunit boosting.

Whereas several recent AIDS vaccine strategies have protected rhesus macaques against a pathogenic simian/human immunodeficiency virus (SHIV)(89.6P) challenge, similar approaches have provided only modest, transient reductions in viral burden after challenge with virulent, pathogenic SIV, which is more representative of HIV infection of people. We show here that priming with replicating adenovirus recombinants encoding SIV env/rev, gag, and/or nef genes, followed by boosting with SIV gp120 or an SIV polypeptide mimicking the CD4 binding region of the envelope, protects rhesus macaques from intrarectal infection with the highly pathogenic SIV(mac251). Using trend analysis, significant reductions in acute-phase and set point viremia were correlated with anti-gp120 antibody and cellular immune responses, respectively. Within immunization groups exhibiting significant protection, a subset (39%) of macaques have exhibited either no viremia, cleared viremia, or controlled viremia at the threshold of detection, now more than 40 weeks postchallenge. This combination prime-boost strategy, utilizing replication competent adenovirus, is a promising alternative for HIV vaccine development.

Adenoviridae↗

PubMed2003

Urocortin in the central nervous system of a primate (Cebus apella): sequencing, immunohistochemical, and hybridization histochemical characterization.

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. Of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.

Amino Acid Sequence↗

PubMed2003

Non-small-cell lung cancer molecular signatures recapitulate lung developmental pathways.

Current paradigms hold that lung carcinomas arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest lung tumor cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected non-small-cell lung tumors. We determined the 100 top-ranked marker genes for adenocarcinoma, squamous cell, large cell, and carcinoid using nearest neighbor analysis. Results were validated by immunostaining for 11 selected proteins using a tissue microarray representing 80 tumors. Gene expression data of lung development were accessed from a publicly available dataset generated with the murine Mu11k genome microarray. Self-organized mapping identified two temporally distinct clusters of murine orthologues. Supervised clustering of lung development data showed large-cell carcinoma gene orthologues were in a cluster expressed in pseudoglandular and canalicular stages whereas adenocarcinoma homologues were predominantly in a cluster expressed later in the terminal sac and alveolar stages of murine lung development. Representative large-cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nucleus and are associated with cell cycle and proliferation. In contrast, adenocarcinoma genes are associated with lung-specific transcription pathways (SFTPB, TTF-1), cell adhesion, and signal transduction. In sum, non-small-cell lung tumors histology gene profiles suggest mechanisms relevant to ontogeny and clinical course. Adenocarcinoma genes are associated with differentiation and glandular formation whereas large-cell genes are associated with proliferation and differentiation arrest. The identification of developmentally regulated pathways active in tumorigenesis provides insights into lung carcinogenesis and suggests early steps may differ according to the eventual tumor morphology.

Adult↗

PubMed2003

[Study on the function localization during different brain calculation tasks].

The aim of this study is to define the anatomical localization of corresponding brain function area during calculating. The activating modes in brain during continuous silent calculating subtraction and repeated silent reading multiplication table were compared and investigated. Fourteen volunteers of right-handedness were enrolled in this experiment. The quite different reaction models in brain area during the two models of calculation revealed that there are different processing pathways in brain during these two operating tasks. During continuous silent calculating, the function areas were found localized on the posterior portion of superior and middle gyrus of frontal lobe and the lobule of posterior parietal lobe (P < 0.01, T = 5.41), demonstrating that these function areas play an important role in the performance of calculation and working memory. During repeated silent reading multiplication table, the activating cluster was found only located in in the gyri occipital lateral(P < 0.01, T = 4.77).

Adult↗

PubMed2002

Approach to establishing a liver targeting gene therapeutic vector using naturally occurring defective hepatitis B viruses devoid of immunogenic T cell epitope.

The development of liver-directed virus vector may play a crucial role in hepatic gene therapy. Hepatitis B virus (HBV) is the only known DNA virus that has hepatocyte specificity. In order to construct an efficient HBV-based vector for targeting the liver, we studied the potential use of naturally occurring defective HBVs obtained from hepatitis patients. The enhanced green fluorescent protein (EGFP) gene or small tag sequences (Flag) were introduced in frame into the deleted sites of the defective HBVs. One HBV defective in site for putative T cell epitope and a part of the polymerase gene tolerated EGFP insertion and was successfully packaged. This defective recombinant HBV harboring 48 bp Flag tag sequence instead of EGFP (rHBV-7-Flag) replicated well. Human primary hepatocytes could uptake rHBV-7-Flag virions, though in a low frequency, when exposed to the virions at a high density in the culture medium, and also express Flag tag sequences. This defective HBV-based vector may have a potential application in liver targeting gene therapy.

Cell Line↗

PubMed2002

Molecular cloning, and characterization and expression of dihydrolipoamide acetyltransferase component of murine pyruvate dehydrogenase complex in bile duct cancer cells.

BACKGROUND: The association between the dihydrolipoamide acetyltransferase component (E2) of pyruvate dehydrogenase complex (PDC) and primary biliary cirrhosis (PBC) is clinically established. However, the detailed pathological function of the PDC-E2 gene is as yet unclear. In order to study the gene function in knockout and transgenic mouse models, we cloned and characterized the mouse PDC-E2 (mPDC-E2) gene. Because the expression level of PDC-E2 was elevated in PBC bile duct cells, we tried to construct a bile duct carcinoma cell line that overexpressed PDC-E2 as a PBC cell model. METHODS: The mPDC-E2 cDNA was obtained by the 3'Race method. We overexpressed this gene in KMBC cells, using a retrovirus vector. The transcript and translated protein of mPDC-E2 were detected by Northern blot and Western blot, respectively. RESULTS: The deduced amino-acid sequence from the cloned cDNA indicated that the fully mature protein consisted of 557 amino-acid residues, with a calculated molecular mass of 59kD. This mature protein was highly consistent with those of previously reported rat and human PDC-E2, which possessed three structurally identifiable regions: the lipoyl-bearing domain, the E3-binding site, and the catalytic domain. Mouse fibroblast NIH3T3 cells expressed one species of mPDC-E2 mRNA, 3.5kb in length. We also successfully constructed a stable KMBC cell line overexpressing the PDC-E2. CONCLUSIONS: This is the first report of the mPDC-E2 sequence and is valuable for further investigation of PDC-E2 gene function in transgenic or knockout mouse models. The PDC-E2 overexpressing KMBC cell line can be used to study alterations in signal transduction or gene expression profiles in PBC bile duct.

Acetyltransferases↗

PubMed2002

Absolute quantification of cerebral blood flow with magnetic resonance, reproducibility of the method, and comparison with H2(15)O positron emission tomography.

While H2(15)O positron emission tomography (PET) is still the gold standard in the quantitative assessment of cerebral perfusion (rCBF), its technical challenge, limited availability, and radiation exposure are disadvantages of the method. Recent work demonstrated the feasibility of magnetic resonance (MR) for quantitative cerebral perfusion imaging. There remain open questions, however, especially regarding reproducibility. The main purpose of this study was to assess the accuracy and reproducibility of MR-derived flow values to those derived from H2(15)O PET. Positron emission tomography and MR perfusion imaging was performed in 20 healthy male volunteers, who were chronic smokers, on day 1 and day 3 of a 4-day hospitalization. Subjects were randomly assigned to one of two groups, each with 10 subjects. One group was allowed to smoke as usual during the hospitalization, while the other group stopped smoking from day 2. Positron emission tomography and MR images were coregistered and rCBF was determined in two regions of interest, defined over gray matter (gm) and white matter (wm), yielding rCBF(PET)gm, rCBF(MR)gm, rCBF(PET)wm, and rCBF(MR)wm. Bland-Altman analysis was used to investigate reproducibility by assessing the difference rCBFday3 - rCBFday1 in eight continual-smoker volunteers. The analysis showed a good reproducibility for PET, but not for MR. Mean +/- SD of the difference rCBFday3 - rCBFday1 in gray matter was 6.35 +/- 21.06 and 0.49 +/- 5.27 mL x min(-1) x 100 g(-1) for MR and PET, respectively; the corresponding values in white matter were 2.60 +/- 15.64 and -1.14 +/- 4.16 mL x min(-1) x 100 g(-1). The Bland-Altman analysis was also used to assess MRI and PET agreement comparing rCBF measured on day 1. The analysis demonstrated a reasonably good agreement of MR and PET in white matter (rCBF(PET)wm - rCBF(MR)wm; -0.09 +/- 7.23 mL x min(-1) x 100 g(-1)), while in gray matter a reasonable agreement was only achieved after removing vascular artifacts in the MR perfusion maps (rCBF(PET)gm - rCBF(MR)gm; -11.73 +/- 14.52 mL x min(-1) x 100 g(-1)). In line with prior work, these results demonstrate that reproducibility was overall considerably better for PET than for MR. Until reproducibility is improved and vascular artifacts are efficiently removed, MR is not suitable for reliable quantitative perfusion measurements.

Adult↗

PubMedDate not supplied

Cystathionine beta-synthase deficiency: effects of betaine supplementation after methionine restriction in B6-nonresponsive homocystinuria.

PURPOSE: For treatment of cystathionine beta-synthase (CbetaS) deficiency, we determined the effect of betaine (N,N,N-trimethylglycine) therapy and examined the genotype-phenotype relationships to betaine. METHODS: In five patients with B6-nonresponsive homocystinuria, we defined the CbetaS genotypes and determined metabolic responses to betaine as an additive to traditional dietary methionine restriction. RESULTS: After betaine therapy, tHcy declined (mean 47.4 micromol/L; range: -21.2 to -104.0 micromol/L; P=0.02), whereas total plasma cysteine and methionine did not change. Plasma methionine/tHcy ratios increased by 5.45 (range: +1.5 to 15.3; P=0.05) inpatients with B6-nonresponsive alleles. CONCLUSION: Betaine improves metabolic control in B6-nonresponsive patients with homocystinuria after optimum dietary control.

Adolescent↗