Biomedical subjects

Chao Zhao

Publications and source records attributed to Chao Zhao.

26 records · Page 2Linked to original sources

PubMed2004

[Study of solid-phase time-resolved fluorescence label immunoassay].

This paper describes optimal conditions for HBsAbIgG labeling with a new fluorescence probe, 4,7-bis-chorosulfophenyl-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA) for the solid phase time-resolved fluorimmunoassay (TRFIA). The result of experiment under states clearly that BCPDA may react with protein under relative mild condition. The relative bioactivity of reacted protein was more than 80%. The labeling molar ratio of BCPDA for HBsAbIgG was 45-70. The recovery was higher than 80%. Protein-BCPDA-Eu3+ complex is stable. It can emit very high fluorescence intensity with very long fluorescence life times. The fluorescence of Protein-BCPDA-Eu3+ complex has a very large stokes shift (270 nm). The emission band at 611.2 nm is very narrow. The research provides the base for developing non-isotopic immunoassay technique and clinical medical diagnosis.

Fluorescence↗

PubMed2003

Lentiviral vectors for gene delivery to normal and demyelinated white matter.

Lentiviral vectors are increasingly used for gene delivery to neurons and in experimental models of neurodegeneration. Their use in gene delivery to white matter and their potential value in preventing or repairing CNS demyelination has received less attention. Here we show using a VSV-G-pseudotyped HIV-derived vector expressing the marker gene LacZ that lentiviral vectors transduce the major macroglial cell types present in normal white matter (astrocytes, oligodendrocytes, and oligodendrocyte progenitors). Injection of lentiviral vectors causes an inflammatory response at the injection site characterized by OX42(+) and ED1(+) macrophages, but only a few CD8(+) and no CD4(+) lymphocytes, and mild demyelination. Injection of lentiviral vectors into areas of toxin-induced demyelination resulted in significant numbers of cells expressing the marker gene and was a more effective means of gene delivery than was a LacZ-expressing murine retroviral vector.

Animals↗

PubMed2003

Increasing local levels of neuregulin (glial growth factor-2) by direct infusion into areas of demyelination does not alter remyelination in the rat CNS.

Glial growth factor-2 (GGF-2) is a neuronally derived isoform of neuregulin shown in vitro to promote proliferation and survival of oligodendrocytes, the myelinating cells of the CNS. Enhanced remyelination has been demonstrated in vivo following systemic delivery of human recombinant GGF-2 (rhGGF-2) in experimental autoimmune encephalomyelitis (EAE). However, it is uncertain whether this is the result of direct effects of rhGGF-2 on cells of the oligodendrocyte lineage or due to modulation of the immune or inflammatory response. If this enhanced remyelination was due to direct effects of rhGGF-2 on cells of the oligodendrocyte lineage then one would expect rhGGF-2 to induce a similar proremyelinating response in nonimmune, gliotoxin models of demyelination. Using a gliotoxin model of demyelination we were therefore able to ascertain the in vivo effect of rhGGF-2 following local CNS delivery in a model that is not confounded by the concurrent presence of an immune-mediated process. No significant alteration in the rate or character of remyelination was evident following local delivery as compared to controls, and indeed nor following systemic delivery in the gliotoxin model. The results of this study therefore indicate that both direct infusion and systemic delivery of rhGGF-2 do not alter remyelination in a nonimmune, gliotoxin model of demyelination. This suggests that the proremyelinating effects of systemically delivered rhGGF-2 in EAE are unlikely to be due to direct effects on the oligodendrocyte lineage, but may be mediated by rhGGF-2 inducing an environment more favourable to remyelination, possibly through modulation of the immune response.

Animals↗

PubMed2002

Ageing and CNS remyelination.

Remyelination of demyelinated axons in the CNS is a regenerative process that, like many others, becomes less efficient with age. This article reviews a series of studies in which toxin models of demyelination have been used to characterize this phenomenon. The delayed rate of remyelination in older animals is associated with a decrease in the rate of oligodendrocyte progenitor recruitment and in the rate at which the recruited cells differentiate into remyelinating oligodendrocytes. The differences in the behaviour of oligodendrocyte lineage cells during remyelination in young and old animals are related to the age-related changes that occur in the expression of growth factors that affect the proliferation, migration and differentiation of oligodendrocyte progenitors, and in the inflammatory process associated with toxin-induced demyelination. Based on these differences, a conceptual framework is proposed to explain the age-associated effects on remyelination, which we have called the dysregulation hypothesis, and the feasibility of reversing these effects is discussed.

Aging↗

PubMed2002

The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation.

The age-associated decrease in the efficiency of CNS remyelination has clear implications for recovery from demyelinating diseases such as multiple sclerosis (MS) that may last for several decades. Developing strategies to reverse the age-associated decline requires the identification of how the regenerative process is impaired. We addressed whether remyelination becomes slower because of an impairment of recruitment of oligodendrocyte progenitors (OPs) or, as is the case in some MS lesions, an impairment of OP differentiation into remyelinating oligodendrocytes. The OP response during remyelination of focal, toxin-induced CNS demyelination in young and old rats was compared by in situ hybridization using probes to two OP-expressed mRNA species: platelet-derived growth factor-alpha receptor and the OP transcription factor myelin transcription factor 1 (MyT1). We found that the expression patterns for the two OP markers are very similar and reveal a delay in the colonization of the demyelinated focus with OPs in the old animals compared with the young animals. By comparing the mRNA expression pattern of MyT1 with that of the myelin proteins myelin basic protein and Gtx, we found that in the old animals there is also a delay in OP differentiation that increases with longer survival times. These results indicate that the age-associated decrease in remyelination efficiency occurs because of an impairment of OP recruitment and the subsequent differentiation of the OPs into remyelinating oligodendrocytes, and that strategies aimed at ameliorating the age-associated decline in remyelination efficiency will therefore need to promote both components of the regenerative process.

Age Factors↗

PubMed2002

Expression of the POU-domain transcription factors SCIP/Oct-6 and Brn-2 is associated with Schwann cell but not oligodendrocyte remyelination of the CNS.

The class III POU-domain transcription factor SCIP/Oct-6 is expressed by promyelinating Schwann cells and, in tissue culture, by oligodendrocyte progenitors (OPs), but is down-regulated in both cells types as they differentiate. Although the expression of SCIP/Oct-6 has been examined in peripheral nerve remyelination, its expression in CNS remyelination has not been addressed. Using a toxin model of demyelination, in which the demyelinated axons are remyelinated in an age-dependent manner by both oligodendrocytes and Schwann cells, we have compared the expression of SCIP/Oct-6 mRNA with that of an OP marker (PDGF-alphaR), a marker of myelinating oligodendrocytes (PLP), and markers of myelinating Schwann cells (P(0) and Krox-20) by in situ hybridization. We have found that the expression of SCIP/Oct-6 mRNA precedes that of P(0) and Krox-20 mRNA expression, but bears little correlation with the expression profiles of either PDGF-alphaR or PLP mRNA. Moreover, there is a spatial correlation between the expression SCIP/Oct-6 mRNA and that of P(0) but not of PDGF-alphaR. These results indicate that SCIP/Oct-6 expression following CNS demyelination is associated with Schwann cell and not oligodendrocyte remyelination. We have also shown that another POU-domain transcription factor, Brn-2, is expressed during CNS remyelination, but that like SCIP/Oct-6, it too has an expression profile indicating that it is associated with the Schwann cell component of remyelination. In addition, we show that Brn-2 expression in Schwann cells is not restricted to CNS remyelination but is also expressed in a similar manner to SCIP/Oct-6 during Schwann cell myelination of neonatal peripheral nerves and regenerating transected adult nerve and in cultured Schwann cells following induction of elevated cAMP levels.

Animals↗

PubMed2002

Stimulation of acetyl-CoA carboxylase gene expression by glucose requires insulin release and sterol regulatory element binding protein 1c in pancreatic MIN6 beta-cells.

Acetyl-CoA carboxylase I (ACCI) is a key lipogenic enzyme whose induction in islet beta-cells may contribute to glucolipotoxicity. Here, we provide evidence that enhanced insulin release plays an important role in the activation of this gene by glucose. Glucose (30 vs. 3 mmol/l) increased ACCI mRNA levels approximately 4-fold and stimulated ACCI (pII) promoter activity >30-fold in MIN6 cells. The latter effect was completely suppressed by blockade of insulin release or of insulin receptor signaling. However, added insulin substantially, but not completely, mimicked the effects of glucose, suggesting that intracellular metabolites of glucose may also contribute to transcriptional stimulation. Mutational analysis of the ACCI promoter, and antibody microinjection, revealed that the effect of glucose required sterol response element binding protein (SREBP)-1c. Moreover, adenoviral transduction with dominant-negative-acting SREBP1c blocked ACCI gene induction, whereas constitutively active SREBP1c increased ACCI mRNA levels. Finally, glucose also stimulated SREBP1c transcription, although this effect was independent of insulin release. These data suggest that glucose regulates ACCI gene expression in the beta-cell by complex mechanisms that may involve the covalent modification of SREBP1c. However, overexpression of SREBP1c also decreased glucose-stimulated insulin release, implicating SREBP1c induction in beta-cell lipotoxicity in some forms of type 2 diabetes.

Acetyl-CoA Carboxylase↗

PubMed2002

Prognosis of hepatic cirrhosis patients with esophageal or gastric variceal hemorrhage: multivariate analysis.

OBJECTIVE: To study the effect of bacterial infection, use of antibiotics, active bleeding at endoscopy, and the severity of liver disease as prognostic factors in hepatic cirrhotic patients during the first 5 days after the episode of esophageal or gastric variceal hemorrhage. METHODS: Seventy-six hepatic cirrhosis patients with esophageal or gastric variceal bleeding were enrolled. Bleeding was managed in a standardized protocol using octreotide and vasopressin in sclerotherapy or band ligation for active bleeding at endoscopy. The screening protocol for bacterial infection consisted of chest radiograph; blood, urine and ascitic fluid cultures; the severity of liver disease shown by Child-Pugh score. RESULTS: Active bleeding was observed at endoscopy in 40 patients (53%). Failure to control bleeding within 5 days occurred in 36 patients (45%). Empirical antibiotic treatment was used in 53 patients (67%), whereas bacterial infections were documented in 43 patients (57%). Multivariate analysis showed that proven bacterial infection (P<0.01) or antibiotic use (P<0.05) as well as active bleeding at endoscopy (P<0.01) and Child-Pugh score (P<0.01) were independent prognostic factors of failure to control bleeding. CONCLUSION: Bacterial infection is associated with failure to control esophageal or gastric variceal bleeding in hepatic cirrhotic patients.

Bacterial Infections↗