[Epidemiological surveillance of rabies in 1999-2003 in Jiangsu Province].
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Adolescent↗
Biomedical subjects
Li Song
Publications and source records attributed to Li Song.
Morphine enhances HIV infection of neonatal macrophages.
Perinatal transmission of HIV accounts for almost all new HIV infections in children. There is an increased risk of perinatal transmission of HIV with maternal illicit substance abuse. Little is known about neonatal immune system alteration and subsequent susceptibility to HIV infection after morphine exposure. We investigated the effects of morphine on HIV infection of neonatal monocyte-derived macrophages (MDM). Morphine significantly enhanced HIV infection of neonatal MDM. Morphine-induced HIV replication in neonatal MDM was completely suppressed by naltrexone, the opioid receptor antagonist. Morphine significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of macrophage inflammatory protein-1beta in neonatal MDM. Thus, morphine, most likely through alteration of beta-chemokines and CCR5 receptor expression, enhances the susceptibility of neonatal MDM to HIV infection, and may have a cofactor role in perinatal HIV transmission and infection.
Analgesics, Opioid↗
Neural network analysis of lymphoma microarray data: prognosis and diagnosis near-perfect.
BACKGROUND: Microarray chips are being rapidly deployed as a major tool in genomic research. To date most of the analysis of the enormous amount of information provided on these chips has relied on clustering techniques and other standard statistical procedures. These methods, particularly with regard to cancer patient prognosis, have generally been inadequate in providing the reduced gene subsets required for perfect classification. RESULTS: Networks trained on microarray data from DLBCL lymphoma patients have, for the first time, been able to predict the long-term survival of individual patients with 100% accuracy. Other networks were able to distinguish DLBCL lymphoma donors from other donors, including donors with other lymphomas, with 99% accuracy. Differentiating the trained network can narrow the gene profile to less than three dozen genes for each classification. CONCLUSIONS: Here we show that artificial neural networks are a superior tool for digesting microarray data both with regard to making distinctions based on the data and with regard to providing very specific reference as to which genes were most important in making the correct distinction in each case.
Algorithms↗
CCR5 expression and beta-chemokine production during placental neonatal monocyte differentiation.
The stage of maturation of monocytes affects their susceptibility to HIV infection. The beta-chemokines and their receptor CCR5 play a crucial role in inflammatory reactions and HIV infection. We therefore examined the correlation between the expression of CCR5 and beta-chemokine production and the susceptibility to HIV infection during cord monocyte (CM) differentiation into macrophages. CM and CM-derived macrophages (CMDM) were examined for beta-chemokine and CCR5 expression. The susceptibility of the CM cultured in vitro at different time points to HIV infection was also determined. Although the levels of CCR5 mRNA expression in freshly isolated CM are comparable to those in CMDM, CM had significantly lower levels of CCR5 protein on the cell surface than CMDM did. Steady increase of CCR5 protein expression on the cell surface was observed during CM differentiation into macrophages. The CCR5 expression correlated with the increased susceptibility to HIV infection by CMDM. Although there was no significant difference in endogenous beta-chemokine production between CM and CMDM, HIV infection of CMDM significantly enhanced production of macrophage inflammatory protein-1alpha and -1beta. CCR5 receptor plays a critical role in HIV infection of neonatal blood monocyte/macrophages.
Cell Differentiation↗
Interleukin-1beta induces macrophage inflammatory protein-1beta expression in human hepatocytes.
The investigation of factors that regulate expression of CC-chemokines, the important mediators in immune responses and inflammation processes, has an important significance in understanding the immunopathogenesis of liver diseases. We examined the role of interleukin-1beta (IL-1beta), a multifunctional cytokine, in regulating the expression of macrophage inflammatory protein (MIP)-1beta in human hepatocytes (Huh7 and HepG2). IL-1beta significantly enhanced MIP-1beta expression in these cells at both the mRNA and protein levels. Cytokine-enriched supernatants from monocyte-derived macrophage (MDM) cultures also induced MIP-1beta expression. IL-1beta is responsible for MDM supernatant-mediated up-regulation of MIP-1beta since the antibody to IL-1beta abolished MDM supernatant action. Investigation of the mechanism involved in MIP-1beta induction by IL-1beta showed that IL-1beta activated the nuclear factor kappa B (NF-kappaB) promoter in Huh7 cells. In addition, caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-kappaB, not only abolished IL-1beta-mediated NF-kappaB promoter activation, but also blocked IL-1beta-induced MIP-1beta expression. These observations suggest that IL-1beta-mediated up-regulation of MIP-1beta production in the hepatic cells may contribute a critical mechanism for continuous recruitment of inflammatory cell to liver and maintenance of inflammation.
Caffeic Acids↗
Characterization of lipoproteins from the turtle, Trachemys scripta elegans, in fasted and fed states.
The lipid and apolipoprotein composition of VLDL, IDL, LDL, HDL(2) and HDL(3) were examined in the turtle, Trachemys scripta elegans, in fasted and fed states. The lipid composition of turtle lipoproteins was very similar to their human counterparts. The major apolipoprotein found in LDL, IDL and VLDL, which has a molecular weight of approximately 550 kD, is a homologue of apoB100. The major apolipoprotein found in both HDL(2) and HDL(3), has a molecular weight of 28-kD and is homologous to human apoA-I. HDL(3) also contains a 6.5 kD protein that is homologous to apoA-II, while HDL(2) has two low molecular weight proteins of 6 kD and 7 kD which are also found on the triglyceride rich lipoproteins (TRL). The 7 kD protein is homologous to apoC-III, while the 6 kD protein has a similar size and distribution as apoC-II or apoC-I. In addition, HDL(2) also possesses a protein of 15.8 kD that has no obvious mammalian homologue. In both size and apolipoprotein composition, turtle HDL(2) resembles human HDL(2b) while turtle HDL(3) resembles human HDL(3). In the fasted state, turtles contained very little TRL. When fed a high fat diet, the amount of IDL and LDL sized particles increased significantly.
Amino Acid Sequence↗
Interleukin-1beta stimulates macrophage inflammatory protein-1alpha and -1beta expression in human neuronal cells (NT2-N).
Chemokines are important mediators in immune responses and inflammatory processes of neuroimmunologic and infectious diseases. Although chemokines are expressed predominantly by cells of the immune system, neurons also express chemokines and chemokine receptors. We report herein that human neuronal cells (NT2-N) produce macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha and MIP-1beta), which could be enhanced by interleukin (IL)-1beta at both mRNA and protein levels. The addition of supernatants from human peripheral blood monocyte-derived macrophage (MDM) cultures induced MIP-1beta mRNA expression in NT2-N cells. Anti-IL-1beta antibody removed most, but not all, of the MDM culture supernatant-induced MIP-1beta mRNA expression in NT2-N cells, suggesting that IL-1beta in the MDM culture supernatants is a major factor in the induction of MIP-1beta expression. Investigation of the mechanism(s) responsible for IL-1beta-induced MIP-1alpha and -1beta expression demonstrated that IL-1beta activated nuclear factor kappa B (NF-kappaB) promoter-directed luciferase activity in NT2-N cells. Caffeic acid phenethyl ester, a potent and specific inhibitor of activation of NF-kappaB, not only blocked IL-1beta-induced activation of the NF-kappaB promoter but also decreased IL-1beta-induced MIP-1alpha and -1beta expression in NT2-N cells. These data suggest that NF-kappaB is at least partially involved in the IL-1beta-mediated action on MIP-1alpha and -1beta in NT2-N cells. IL-1beta-mediated up-regulation of beta-chemokine expression may have important implications in the immunopathogenesis of inflammatory diseases in the CNS.
Cell Line↗
Unfolding the pathophysiological role of bioactive lysophospholipids.
Lysophospholipids (LPLs), including glycerol- and sphingoid-based lipids, stimulate cell signaling and play important pathophysiological roles in humans and other animals. These LPLs include lysophosphatidic acid (LPA), lysophosphatidylinositol (LPI), lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), sphingosine-1-phosphate (S1P), and sphingosylphosphorylcholine (SPC). Analyses of LPLs in human body fluids from subjects with different pathophysiological conditions reveal not only the relevance of LPLs in human diseases, but also their potential application as biomarkers and/or therapeutic targets. In recent years, the identification and/or characterization of the plasma membrane receptors for LPLs and enzymes regulating the metabolism of LPLs have greatly facilitated our understanding of their role and signaling properties. In vitro and in vivo functional and signaling studies have revealed the broad and potent biological effects of LPLs and the mechanisms of LPL actions in different cellular systems. Development of specific antagonists for each of the LPL receptors will provide powerful tools for dissecting signaling pathways mediated by receptor subtypes. More importantly, these antagonists may serve as therapeutics for relevant diseases. Genetic depletion of LPL receptors in mice has provided and will continue to provide critical information on the pathophysiological roles of LPL receptors. It is important to further evaluate the significance of targeting these bioactive LPL receptors, their downstream signaling molecules, and/or metabolic enzymes in the treatment of cancers and other diseases.
Animals↗
Functional expression of CCR2 by human fetal astrocytes.
Astrocytes from different sources bind the chemokine monocyte chemoattractant factor (MCP-1), yet functional expression in these cells of CCR2, the major receptor for this ligand, has been a matter of controversy. Here we show that cultured human fetal astrocytes express CCR2 at the mRNA and protein levels, and display chemotaxis and calcium flux in response to MCP-1. Surface CCR2 protein expression and MCP-1 binding activity were observed to undergo near parallel downmodulation and recovery following MCP-1 exposure, supporting the argument that CCR2, and not another receptor, mediates MCP-1 ligation in these cells. Downmodulation was further determined to occur via receptor internalization, and to apparently proceed via both clathrin-coated vesicles and caveolae, the latter being a novel mode for the endocytosis of chemokine receptors. Insofar as MCP-1 is thought to mediate inflammatory and developmental processes within the central nervous system (CNS), such astrocyte responses to this chemokine are likely to significantly impact physiological and pathophysiological events at the blood-brain barrier and within the CNS parenchyma.
Astrocytes↗
A non-peptide substance P antagonist down-regulates SP mRNA expression in human mononuclear phagocytes.
Substance P (SP), a potent modulator of neuroimmunoregulation, exerts its activity by binding to the neurokinin-1 receptor (NK-1R). The SP-NK-1R interaction is important in inflammation and viral infections, including HIV infection of human immune cells. We recently demonstrated that SP modulates HIV replication and that a non-peptide SP antagonist CP-96,345 inhibits HIV replication in human monocyte-derived macrophages (MDM) by affecting the SP-NK-1R interaction. In order to examine the effect of the SP antagonist on SP mRNA expression, MDM was incubated with or without CP-96,345 in the presence or absence of HIV infection. SP mRNA expression in these cells was then determined by real-time PCR technology. The effect of CP-96,345 on chemokine gene expression was also investigated by using a cDNA array assay. CP-96,345 down-regulated SP mRNA expression and antagonized exogenous SP-enhanced SP expression at the mRNA level, suggesting that SP autocrine regulation was interrupted by CP-96,345. CP-96,345 inhibited HIV replication in MDM, associated with down-regulated SP mRNA expression in comparison to HIV infection controls. In parallel with down-regulated SP and CCR5 mRNA expression, cDNA array assays indicated that CP-96,345 treatment also inhibited IL-8 gene expression, while enhancing expression of fractalkine and monocyte chemotactic protein-3 (MCP-3). Since SP plays an important role in inflammation and viral infections, these studies may have potential applications for therapeutic intervention of inflammation and viral infection of immune cells.
Anti-Inflammatory Agents, Non-Steroidal↗
Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes.
BACKGROUND: Acute and chronic alcohol abuse impairs various functions of the immune system and thus has been implicated as a cofactor in HIV infection. The mechanisms by which alcohol affects the function of human immune cells that are the targets for HIV are unknown. METHODS: Human blood monocyte-derived macrophages (MDM) were incubated with or without alcohol (10-40 mM) for 24 hr and then infected with HIV for 24 hr. Culture supernatants were harvested for HIV reverse transcription assay. HIV entry receptor (CCR5, CD4, and CXCR4) expression was determined by reverse transcription-polymerase chain reaction and flow cytometry assays. Beta-chemokines were analyzed using enzyme-linked immunosorbent assay. Different HIV strains (Bal, SF-162, 89.6, and UG024) were used for infection experiments. In addition, ADA (macrophage-tropic strain) and murine leukemia virus envelope-pseudotyped HIV infection was carried out. RESULTS: Although alcohol had little effect on HIV T-lymphocyte-tropic strain infection, it significantly enhanced HIV R5 strain infection in MDM. The enhancing effect of alcohol on the HIV R5 strain was further evidenced by the observation that the R5 (ADA) strain envelope-pseudotyped HIV infection is markedly increased by alcohol, whereas murine leukemia virus envelope-pseudotyped HIV infection was not affected. Alcohol significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of beta-chemokines by MDM. CONCLUSION: Alcohol, through the down-regulation of beta-chemokine production and the up-regulation of CCR5 receptor expression, enhances HIV R5 strain infection of MDM and may have an important role as a cofactor in the progression of HIV disease.
Cells, Cultured↗
[Establishment of an indirect enzyme-linked immunosorbent assay for detecting the specific IgM antibodies in patients with echovirus infection].
BACKGROUND: To provide a simple, specific and early serodiagnostic technique for the patients with aseptic meningitis caused by echovirus. METHODS: An indirect enzyme-linked immunosorbent assay (ELISA) has been developed to detect echovirus-IgM and the specificity and availability of the assay were also examined. RESULTS: In 78 cerebrospinal fluid (CSF) specimens which came from the children with aseptic meningitis, the positive rate was 17.9(14/78). In 64 CSF collected from non-aseptic meningitis (bacterial meningitis and cerebral trauma), the positive rate was 1.56(1/64). In 5 CSF specimens which were ELISA positive, the positive rate of neutralization test (NT) was 4/5, all the specimens which were ELISA negative were NT negative. In this assay there was no cross-reaction with poliovirus, Coxsackie virus B type 1-6 and A type 7. By blocking and destructive test of specific IgM, all CSF specimens with ELISA positive became negative. CONCLUSIONS: The established indirect ELISA was specific and reliable. The te st was quick, simple and available, which is suitable for early and specific clinical diagnosis, and will be greatly significant to clinical treatment.
Adult↗
Culture of murine brain microvascular endothelial cells that maintain expression and cytoskeletal association of tight junction-associated proteins.
A readily obtainable in vitro paradigm of the blood-brain barrier (BBB) would offer considerable benefits. Toward this end, in this study, we describe a novel method for purifying murine brain microvascular endothelial cells (BMEC) for culture. The method uses limited collagenase-dispase digestion of enriched brain microvessels, followed by immunoisolation of digested, microvascular fragments by magnetic beads coated with antibody to platelet-endothelial cell adhesion molecule-1. When plated onto collagen IV-coated surfaces, these fragments elaborated confluent monolayers of BMEC that expressed, as judged by immunocytochemistry, the adherens junction-associated proteins, VE-cadherin and beta-catenin, as well as the tight junction (TJ)-associated proteins, claudin-5, occludin, and zonula occludin-1 (ZO-1), in concentrated fashion along intercellular borders. In contrast, cultures of an immortalized and transformed line of murine brain capillary-derived endothelial cells, bEND.3, displayed diffuse cytoplasmic localization of occludin and ZO-1. This difference in occludin and ZO-1 staining between the two endothelial cell types was also reflected in the extent of association of these proteins with the detergent-resistant cytoskeletal framework (CSK). Although both occludin and ZO-1 largely partitioned with the CSK fraction in BMEC, they were found predominantly in the soluble fraction of bEND.3 cells, and claudin-5 was found associated equally with both fractions in BMEC and bEND.3 cells. Moreover, detergent-extracted cultures of the BMEC retained pronounced immunostaining of occludin and ZO-1, but not claudin-5, along intercellular borders. Because both occludin and ZO-1 are thought to be functionally coupled to the detergent-resistant CSK and high expression of TJs is considered a seminal characteristic of the BBB, these results impart that this method of purifying murine BMEC provides a suitable platform to investigate BBB properties in vitro.
Animals↗
Efficacy of lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy for ovarian cancer.
UNLABELLED: Transfer of the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. Effective gene therapy depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. The purpose of this study was to investigate the anti-tumor effect of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse models were generated with intraperitoneal injection of human epithelial ovarian cancer cells 3AO, which are MUC1-positive, HIV-1-based lentiviral vectors carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK, followed by GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK with GCV inhibited the proliferation and prolonged survival times compared with the control vector. The survival time of animals treated with scFv-VP22-TK/GCV was significantly longer than that of animals treated with VP22-TK/GCV (p = 0.006). CONCLUSION: Our results suggest that MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit ovarian tumor growth and increase survival in a nude mouse model of ovarian carcinoma. These data support the development of this method for human clinical trials.
Animals↗