Biomedical subjects

Hong Hao

Publications and source records attributed to Hong Hao.

5 recordsLinked to original sources

PubMed2005

Critical viscosity exponent for classical fluids.

A self-consistent mode-coupling calculation of the critical viscosity exponent z(eta) for classical fluids is performed by including the memory effect and the vertex corrections. The incorporation of the memory effect is through a self-consistency procedure that evaluates the order parameter and shear momentum relaxation rates at nonzero frequencies, thereby taking their frequency dependence into account. This approach offers considerable simplification and efficiency in the calculation. The vertex corrections are also demonstrated to have significant effects on the numerical value for the critical viscosity exponent, in contrast to some previous theoretical work which indicated that the vertex corrections tend to cancel out from the final result. By carrying out all of the integrations analytically, we have succeeded in tracing the origin of this discrepancy to an error in earlier work. We provide a thorough treatment of the two-term epsilon expansion, as well as a complete three-dimensional analysis of the fluctuating order-parameter and transverse hydrodynamic modes. The study of the interactions of these modes is carried out to high order so as to arrive at z(eta) = 0.0679+/-0.0007 for comparison with the experimentally observed value, 0.0690+/-0.0006 .

Journal Article↗

PubMed2003

Dexamethasone responsive element in the rat Na, K-ATPase beta1 gene coding region.

The Na, K-ATPase plays an essential role in active alveolar epithelial fluid resorption. In fetal and adult alveolar epithelial cells, glucocorticoids (GC) increase Na, K-ATPase activity, mRNA levels, and transcription rate of the beta(1) subunit. In this study, we describe a glucocorticoid responsive element (GRE) in the coding region of the rat Na, K-ATPase beta(1) gene in a rat lung epithelial cell line. Transient transfection experiments with the beta(1) subunit coding region with or without the 5' and 3' untranslated regions demonstrated responsiveness to dexamethasone induction and also identified a GRE at +434 in exon IV. The +434 GRE conferred dexamethasone responsiveness in a heterologous thymidine kinase promoter irrespective of its orientation to the beta(1) promoter. Transcriptional upregulation by dexamethasone was abolished in +434 mutants. Electrophoretic mobility shift assays (EMSA) demonstrated specific binding of nuclear proteins to the +434 GRE and the presence of the GC receptor. This specific binding was inhibited by a GRE previously described in the rat Na, K-ATPase beta(1) gene at -631. In conclusion, we identified a GRE at +434 in the exon IV of the rat Na, K-ATPase beta(1) gene.

Animals↗

PubMed2003

Dexamethasone stimulates transcription of the Na+-K+-ATPase beta1 gene in adult rat lung epithelial cells.

Na+-K+-ATPase plays an essential role in active alveolar epithelial fluid resorption. In fetal and adult alveolar epithelial cells, glucocorticoids (GC) increase Na+-K+-ATPase activity and mRNA levels. We sought to define the mechanism of Na+-K+-ATPase gene upregulation by GC. In a rat alveolar epithelial cell line (RLE), dexamethasone (Dex) increased beta1-subunit Na+-K+-ATPase mRNA expression two- to threefold within 3 h after exposure to the GC. The increased gene expression was due to increased transcription as demonstrated by nuclear run-on assays, whereas mRNA stability remained unchanged. Transient transfection of 5' deletion mutants of a beta1 promoter-reporter construct demonstrated a 1.5- to 2.2-fold increase in promoter activity by Dex. All of the 5' deletion constructs contained partial or palindromic GC regulatory elements (GRE) and responded to GC. The increased expression of promoter reporter was inhibited by RU-486, a GC receptor (GR) antagonist, suggesting the involvement of GR. The palindromic GRE at -631 demonstrated Dex induction in a heterologous promoter construct. Gel mobility shift assays using RLE nuclear extracts demonstrated specific binding to this site and the presence of GR. We conclude that GC directly stimulate transcription of Na+-K+-ATPase beta1 gene expression in adult rat lung epithelial cells through a GR-dependent mechanism that can act at multiple sites.

Age Factors↗

PubMed2003

Modulation of the folate receptor type beta gene by coordinate actions of retinoic acid receptors at activator Sp1/ets and repressor AP-1 sites.

Folate receptor (FR) type beta is a promising target for therapeutic intervention in acute myelogenous leukemia (AML) owing particularly to its specific up-regulation in AML cells by all-trans retinoic acid (ATRA). Here we identify functional elements in the FR-beta gene and examine the molecular mechanism of transcriptional induction of FR-beta by ATRA. The basal promoter activity of FR-beta resulted from synergistic interaction between Sp1 and ets binding sites (EBSs) and repression by upstream AP-1-like elements, whose action required EBSs. A minimal promoter containing the Sp1 and ets elements was ATRA-responsive. The repressor elements bound Fos family proteins; association of the proteins with the repressor elements correlated negatively with FR-beta expression in peripheral blood neutrophils and monocytes and also in KG-1 (AML) cells grown in the absence or in the presence of ATRA. Furthermore, down-regulation of FR-beta in KG-1 cells treated with O-tetradecanoylphorbol 13-acetate (TPA) was accompanied by increased AP-1 binding to the repressor elements. From chromatin immunoprecipitation (ChIP) assays, the nuclear retinoic acid receptor alpha (RARalpha) associated with the Sp1 region, and RARs beta and gamma associated with the AP-1 and Sp1 regions; treatment of KG-1 cells with ATRA did not alter Sp1 binding but increased the association of RARalpha and decreased the association of RARs beta and gamma. ATRA also decreased RAR expression levels. The results suggest that the FR-beta gene is a target for multiple coordinate actions of nuclear receptors for ATRA directly and indirectly acting on a transcriptional complex containing activating Sp1/ets and inhibitory AP-1 proteins. The multiple mechanisms favor the prediction that ATRA will induce FR-beta expression in a broad spectrum of AML cells. Further, optimal FR-beta induction may be expected when all 3 RAR subtypes bind agonist.

Blood Cells↗

PubMed2003

Receptor induction and targeted drug delivery: a new antileukaemia strategy.

Strategic modalities of drug delivery have the potential to greatly improve the therapeutic efficacy of available drugs in acute myelogenous leukaemia (AML). Folate receptor (FR) type beta is selectively expressed on the surface of approximately 70% of AMLs. Increased FR-beta expression in these cells can be induced by all-trans retinoic acid (ATRA) and other retinoid compounds in the absence of terminal differentiation or cell growth inhibition. An apparent post-transcriptional modification prevents FR-beta in normal haematopoietic cells from binding folate, in contrast to AML cells. FR-beta may, therefore, be used as a target for the selective delivery of chemotherapeutic drugs to AML cells; this treatment modality appears to be particularly efficacious when administered in conjunction with retinoid-induction of FR-beta. FR-targeted liposomal drug delivery can also bypass the P-glycoprotein (P-gp)-mediated drug efflux pump commonly associated with multiple drug resistance in AML. The rationale and merits of this novel experimental treatment for AML and the current status of this research are provided.

Animals↗