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Ling Shao

Publications and source records attributed to Ling Shao.

16 recordsLinked to original sources
PubMed2006

Genome scans and gene expression microarrays converge to identify gene regulatory loci relevant in schizophrenia.

Multiple linkage regions have been reported in schizophrenia, and some appear to harbor susceptibility genes that are differentially expressed in postmortem brain tissue derived from unrelated individuals. We combined traditional genome-wide linkage analysis in a multiplex family with lymphocytic genome-wide expression analysis. A genome scan suggested linkage to a chromosome 4q marker (D4S1530, LOD 2.17, theta = 0) using a dominant model. Haplotype analysis using flanking microsatellite markers delineated a 14 Mb region that cosegregated with all those affected. Subsequent genome-wide scan with SNP genotypes supported the evidence of linkage to 4q33-35.1 (LOD = 2.39) using a dominant model. Genome-wide microarray analysis of five affected and five unaffected family members identified two differentially expressed genes within the haplotype AGA and GALNT7 (aspartylglucosaminidase and UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 7) with nominal significance; however, these genes did not remain significant following analysis of covariance. We carried out genome-wide linkage analyses between the quantitative expression phenotype and genetic markers. AGA expression levels showed suggestive linkage to multiple markers in the haplotype (maximum LOD = 2.37) but to no other genomic region. GALNT7 expression levels showed linkage to regulatory loci at 4q28.1 (maximum LOD = 3.15) and in the haplotype region at 4q33-35.1 (maximum LOD = 2.37). ADH1B (alcohol dehydrogenase IB) was linked to loci at 4q21-q23 (maximum LOD = 3.08) and haplotype region at 4q33-35.1 (maximum LOD = 2.27). Seven differentially expressed genes were validated with RT-PCR. Three genes in the 4q33-35.1 haplotype region were also differentially expressed in schizophrenia in postmortem dorsolateral prefrontal cortex: AGA, HMGB2, and SCRG1. These results indicate that combining differential gene expression with linkage analysis may help in identifying candidate genes and potential regulatory sites. Moreover, they also replicate recent findings of complex trans- and cis- regulation of genes.

Adolescent↗
PubMed2006

Immunomodulatory roles of the carcinoembryonic antigen family of glycoproteins.

One of the most remarkable aspects of the immune system is its ability to fashion an immune response most appropriate to the activating stimulus. Although the immune system possesses a number of adaptations to accomplish this, an important theme is local immune regulation by site-specific expression of receptors and ligands. One family of molecules that is gaining attention as modulators of the immune system is the carcinoembryonic antigen cell-adhesion molecule family (CEACAM). Functionally, the carcinoembryonic antigen family can mediate cell-cell contact, host-pathogen interactions, and immune regulation. For example, biliary glycoprotein (CEACAM1) can have direct activity on T cells, leading to the inhibition of helper or cytotoxic T cell function. The expression of carcinoembryonic antigen (CEACAM5) on intestinal epithelial cells is involved in the activation of populations of regulatory CD8(+) T cells, while a distinct subset of regulatory CD8+ T cells is activated by nonspecific cross-reacting antigen (CEACAM6) on placental trophoblasts. Interestingly, the function and phenotype of these cells depend upon the specific member of the carcinoembryonic antigen family expressed, as well as the antigen-presenting molecule with which it associates. Thus, these glycoproteins comprise a family of molecules whose functions can depend on their nature and context.

Bacterial Adhesion↗
PubMed2005

Further evidence that ribavirin interacts with eIF4E.

This commentary discusses the recent reports in RNA by Yan and colleagues and Westman and colleagues of the apparent failure of ribavirin to bind to recombinant eIF4E and inhibit 7-methyl guanosine cap-dependent exogenous mRNA translation of cell extracts in vitro. Measuring binding by using affinity chromatography of matrix-immobilized proteins and by using protein emission fluorescence spectroscopy in the presence of nucleotide ligands, as well as limitations of using cell extracts for the assessment of mechanisms of mRNA translation are discussed. Possible reasons for the discordant findings of Yan and colleagues and Westman and colleagues are suggested, and direct observation of the specific binding of ribavirin to eIF4E by using mass spectrometry is presented.

Eukaryotic Initiation Factor-4E↗
PubMed2005

Activation of CD8+ regulatory T cells by human placental trophoblasts.

The immunological basis by which a mother tolerates her semi-allogeneic fetus remains poorly understood. Several mechanisms are likely to contribute to this phenomenon including active immune regulation by regulatory T cells. In this article, we report that human placental trophoblasts activate a clonal population of CD8(+) T cells with regulatory function. These cells are not MHC class I restricted, but require costimulation through a member of the carcinoembryonic Ag family present on early gestation trophoblasts. These regulatory T cells express the mucosal markers CD101 and CD103 and display selective usage of the TCR gene Vbeta9. CD8(+) T cells isolated from the peripheral blood of pregnant mothers (16-28 wk) also demonstrate expansions in the same Vbeta family (Vbeta9), signaling a possible role for these cells in preventing fetal rejection in vivo. We have previously characterized a subset of CD8(+) regulatory T cells activated by the combination of the nonclassical class I molecule CD1d and a costimulatory molecule of the carcinoembryonic Ag family present on the intestinal epithelium. These data support the concept that distinct regulatory T cell populations exist at different sites and may be regulated locally by unique restriction elements, costimulatory signals, and Ags.

Antigens, CD↗
PubMed2005

Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease.

Mucosal tolerance is believed to be partly mediated by regulatory T cells. Intestinal epithelial cells (IECs) may play an important role in the generation of such regulatory cells, because they are able to process and present Ag to T cells. Furthermore, we have previously demonstrated that IECs are able to generate regulatory CD8(+) T cells in vitro. In the present study, we have analyzed lamina propria (LP) lymphocytes for the presence of such regulatory CD8(+) T cells in normal individuals as well as in patients with inflammatory bowel disease (IBD). The results of the present study show that LP CD8(+) T cells derived from normal controls possess regulatory activity, whereas both unfractionated LP lymphocytes and purified LP CD4(+) T cells do not. The LP CD8(+) T cells suppress Ig production by pokeweed mitogen-stimulated PBMCs by 31-80%, in a cell contact-dependent manner. No significant difference in suppression between CD28(+) and CD28(-)CD8(+) LP T cells was observed. In contrast to CD8(+) T cells from normal LP, CD8(+) T cells isolated from LP of IBD patients, did not suppress Ig production by pokeweed mitogen-stimulated PBMC (five of six ulcerative colitis specimens; six of six Crohn's disease specimens). Furthermore, we demonstrate that the frequency of TCR Vbeta5.1-positive CD8(+) T cells, which we previously have demonstrated to be regulatory and to be expanded by IECs in vitro, is decreased in IBD LP compared with normal LP. In conclusion, this study demonstrates that CD8(+) T cells with regulatory activity are present in the LP of normal healthy individuals, but not in patients with IBD, suggesting that these cells might play an active role in mucosal tolerance.

Adult↗
PubMed2005

Non-classical MHC class I molecules on intestinal epithelial cells: mediators of mucosal crosstalk.

The mucosal immune environment consists of a complex combination of lymphoid cells, non-lymphoid cells, and lumenal bacteria. Signals from lumenal bacteria are constantly transmitted to the underlying tissues across the intestinal epithelial barrier. Intestinal epithelial cells (IECs) can sense these signals, integrate them, and interpret them for lamina propria lymphoid populations. One mechanism by which these signals are communicated is by the expression of non-classical major histocompatibility complex (MHC) class I molecules by IECs. Epithelial cells can express a surprising variety of non-classical MHC class I molecules. In some cases, IECs can act as non-professional antigen-presenting cells utilizing the expression of such non-classical MHC class I molecules to directly present bacterial antigens. In other cases, the expression of non-classical MHC class I molecules may act as a co-stimulatory molecule or adhesion molecule that can modify the mucosal immune response. Finally, the expression of these molecules on IECs can lead to a broad array of responses ranging from tolerance to inflammation. Overall, the IEC, via the expression of non-classical MHC class I molecules, is a central mediator of the constant crosstalk between the intestinal lumen and the mucosal immune system.

Animals↗
PubMed2005

[In vitro propagation of Clematis filamentosa].

The rapid propagation of Clematis filamentosa Dumn by tissue cluture showed that the best explant was young stem. It also showed that the callus can be easily induced in MS + NAA 0.1 mg/L + 6-BA 0.5 mg/L, the medium for the buds differentiation and proliferation was MS + NAA 0.05 mg/L + 6-BA 0.5 mg/L, and the medium for the root growth was MS + NAA 0.1 mg/L. The survival tube seedling can be successfully transplant.

Clematis↗
PubMed2004

Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap.

The eukaryotic translation initiation factor eIF4E is deregulated in many human cancers, and its overexpression in cells leads to malignant transformation. Oncogenic properties of eIF4E are directly linked to its ability to bind 7-methyl guanosine of the 5' mRNA. Here, we observe that the antiviral guanosine analogue ribavirin binds to eIF4E with micromolar affinity at the functional site used by 7-methyl guanosine mRNA cap, competes with eIF4E:mRNA binding, and, at low micromolar concentrations, selectively disrupts eIF4E subcellular organization and transport and translation of mRNAs posttranscriptionally regulated by eIF4E, thereby reducing levels of oncogenes such as cyclin D1. Ribavirin potently suppresses eIF4E-mediated oncogenic transformation of murine cells in vitro, of tumor growth of a mouse model of eIF4E-dependent human squamous cell carcinoma in vivo, and of colony formation of eIF4E-dependent acute myelogenous leukemia cells derived from human patients. These findings describe a specific, potent, and unforeseen mechanism of action of ribavirin. Quantum mechanical and NMR structural studies offer directions for the development of derivatives with improved cytostatic and antiviral properties. In all, ribavirin's association with eIF4E may provide a pharmacologic means for the interruption of posttranscriptional networks of oncogenes that maintain and enhance neoplasia and malignancy in human cancer.

Animals↗
PubMed2004

The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells.

BACKGROUND & AIMS: Previous studies have suggested that intestinal epithelial cells (IECs) may function as antigen-presenting cells for CD4+ and CD8+ T cells. However, these cells fail to express conventional costimulatory molecules (CD80, CD86), leading to the possibility that antigen presented by normal IECs could result in anergy. Other members of the B7 family have recently been identified. B7h interacts with inducible costimulator (ICOS) on T cells and provides a positive signal, whereas B7-H1 and B7-DC interact with PD-1 and transmit an inhibitory signal. Our aim was to determine whether IECs express novel B7 family members and whether these molecules play a role in IEC:T-cell interactions. METHODS: B7h and B7-H1 expression was assessed in isolated IECs and IEC lines. The functional role of B7h and B7-H1 in the interaction between IECs and T cells was assessed in coculture experiments using purified anti-B7h or B7-H1 monoclonal antibodies (mAbs), B7h immunoglobulin (Ig), or B7-H1 fusion proteins. RESULTS: B7h and B7-H1 messenger RNA was detected in IEC lines and IECs from healthy controls and patients with inflammatory bowel disease (IBD). IECs from patients with IBD but not healthy controls expressed B7h and B7-H1 protein on their surface. Proliferation of IEC-stimulated T cells was inhibited only by B7h immunoglobulin treatment, whereas interferon gamma secretion in these cocultures was inhibited by both anti-B7h mAb and B7h Ig. No difference was seen between IBD or normal IEC populations. CONCLUSIONS: These data suggest that the B7h-ICOS costimulatory pathway may be important in IEC:T-cell interactions.

Antigens, CD↗
PubMed2004

Activation of a unique population of CD8(+) T cells by intestinal epithelial cells.

Intestinal epithelial cells may play a role in the regulation of immune responses toward luminal antigens. We show that a subset of CD8(+) T cells undergoes oligoclonal expansion in the intestinal mucosa, probably through interaction with a unique complex expressed on epithelial cells, formed by a CEA subfamily member (gp180) and CD1d. This subset, which is regulatory in vitro, may play a role in the control of intestinal immune responses toward luminal antigens. A lack of expansion of these CD8(+) regulatory T cells, probably related to the defective expression of the gp180/CD1d complex, is observed in inflammatory bowel disease.

CD8-Positive T-Lymphocytes↗
PubMed2003

Neurologic consequences of HIV infection in the era of HAART.

In this brief review, we present a summary of the clinical presentation of HIV-associated dementia (HAD), HAD in the highly active antiretroviral therapy (HAART) era, the immunopathogenesis of HAD, and the possible role of a recently described novel macrophage-derived protein in HAD. Different aspects of the clinical presentation of HAD will be reviewed as well as the results of recent autopsy studies demonstrating that although HAART dramatically decreased the incidence of opportunistic infections and malignancies in the central nervous system, it has reduced but not eliminated HIV encephalopathy. This suggests a direct cytopathic effect of HIV on neuronal tissue. Consequently, the immunopathogenesis of HAD and the role of neurotoxins produced by brain macrophages and microglial cells will be reviewed including the possible role of a recently cloned macrophage-derived proapoptotic factor, soluble HIV apoptotic protein (SHIVA) identified in our laboratory. HAART therapy reduces the incidence of opportunistic infections, the direct pathogenic effect of HIV, especially on neuronal tissue, may become of increasing importance.

AIDS Dementia Complex↗
PubMed2003

Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells.

CD1d is expressed on the surface of professional and nonprofessional APCs, including intestinal epithelial cells (IECs), for a role in the presentation of glycolipid-based antigens to subsets of T cells. The mechanisms that regulate CD1d expression in any cell type are unknown. To investigate the possibility that expression of CD1d is influenced by exogenous factors present within the intestinal lumen, CD1d expression was analyzed in several IEC lines after culturing in the presence of lumenal contents (LC) of the normal human intestine. Exposure of the colon-derived cell lines T84, HT-29, and Caco-2 to soluble LC resulted in a marked induction of CD1d expression as determined by RT-PCR, confocal microscopy, cell surface ELISA, and Western blot analysis. Similarly, exposure of human IECs to LC isolated from mice bred in both specific pathogen-free and germfree conditions also resulted in the induction of CD1d expression, with the maximum CD1d-inducing activity observed in the small intestine. Biochemical and biophysical characterization of the human CD1d-inducing activity identified heat shock protein 110 (Hsp110) as a major functional component of the LC that contributes to CD1d surface regulation, and immunolocalization studies revealed Hsp110 expression in subsets of human IECs in vivo. These data support the presence of a novel autocrine pathway of CD1d regulation by Hsp110.

Amino Acid Sequence↗
PubMedDate not supplied

Transmission scan truncation with small-field-of-view dedicated cardiac SPECT systems: impact and automated quality control.

BACKGROUND: Small-field-of-view (FOV) dedicated cardiac single photon emission computed tomography (SPECT) systems will frequently exhibit severe transmission scan truncation that may degrade attenuation correction (AC). This study evaluated the impact of transmission scan truncation on AC and developed automated transmission scan truncation quality control (ATSTQC) for small-FOV systems. METHODS AND RESULTS: Small-FOV data were simulated from the data of 10 patients acquired by a full-FOV Philips Vertex system. AC images of the full- and small-FOV data were compared by mean and maximum absolute differences of myocardial counts, and differences in stress and rest severity scores were calculated by use of the Emory Cardiac Toolbox.small-FOV systems. ATSTQC was developed to identify critical truncation that significantly increased these indices and then tested with 18 independent patients. Left-side truncation resulted in significant distortion of the quantitative indices. ATSTQC, developed on the condition that left-side truncation is critical, showed high concordance with the qualitative assessment in identification of critical truncation. CONCLUSIONS: Identification of left-side truncation as critical truncation is necessary to judge whether accurate AC can be obtained. The developed ATSTQC can accurately detect critical truncation and will help clinicians decide whether to use AC in a particular study.

Artifacts↗