Biomedical subjects

Xiaoping Zhang

Publications and source records attributed to Xiaoping Zhang.

47 records · Page 3Linked to original sources

PubMed2003

[Dynamic monitoring on land cover in loess hilly and gully area by the methods of RS and GIS].

By the integration of RS and GIS, with the TM data obtained from Landsat 5 in 1990 and the ETMplus data from Landsat 7 in 2000, and after geometrical rectifying and amplifying and man-machine screen decoding data image, the map of eco-environment and land use/cover in Yanhe watershed and its vicinities in 1990 and 2000 was obtained respectively, and the results of statistic analyses showed that in comparing with 1990, the artificial land in 2000 increased by 31%, the area of agricultural land was stable and that of orchard was 2.82 times more, and the area of artificial forest increased remarkably and that of shrub was 6 times more. The coverage rate increased to 13.88%, and the area of wilderness was 44.8% of that in 1990. The quality of eco-environment was improved remarkably in this area.

Agriculture↗

PubMed2002

Paranemic cohesion of topologically-closed DNA molecules.

Specific cohesion of DNA molecules is key to the success of work in biotechnology, DNA nanotechnology and DNA-based computation. The most common form of intermolecular cohesion between double helices is by sticky ends, but sticky ends generated by naturally occurring restriction enzymes may often be too short to bind large constructs together. An alternative form of binding is available through the paranemic crossover (PX) motif. Each of the two components of a PX motif can be a DNA dumbbell or other topologically closed species. Alternate half-turns of the dumbbell are paired intramolecularly. The intervening half-turns are paired with those of the opposite component. We demonstrate the efficacy of PX cohesion by showing that it can result in the 1:1 binding of two triangle motifs, each containing nearly 500 nucleotides. The cohesion goes to completion, demonstrating an alternative to binding nucleic acid molecules through sticky ends.

DNA↗

PubMed2002

Retinoblastoma tumor suppressor targets dNTP metabolism to regulate DNA replication.

The retinoblastoma tumor suppressor, RB, is a negative regulator of the cell cycle that is inactivated in the majority of human tumors. Cell cycle inhibition elicited by RB has been attributed to the attenuation of CDK2 activity. Although ectopic cyclins partially overcome RB-mediated S-phase arrest at the replication fork, DNA replication remains inhibited and cells fail to progress to G(2) phase. These data suggest that RB regulates an additional execution point in S phase. We observed that constitutively active RB attenuates the expression of specific dNTP synthetic enzymes: dihydrofolate reductase, ribonucleotide reductase (RNR) subunits R1/R2, and thymidylate synthase (TS). Activation of endogenous RB and related proteins by p16ink4a yielded similar effects on enzyme expression. Conversely, targeted disruption of RB resulted in increased metabolic protein levels (dihydrofolate reductase, TS, RNR-R2) and conferred resistance to the effect of TS or RNR inhibitors that diminish available dNTPs. Analysis of dNTP pools during RB-mediated cell cycle arrest revealed significant depletion, concurrent with the loss of TS and RNR protein. Importantly, the effect of active RB on cell cycle position and available dNTPs was comparable to that observed with specific antimetabolites. Together, these results show that RB-mediated transcriptional repression attenuates available dNTP pools to control S-phase progression. Thus, RB employs both canonical cyclin-dependent kinase/cyclin regulation and metabolic regulation as a means to limit proliferation, underscoring its potency in tumor suppression.

Adenoviridae↗

PubMed2002

Activation of extracellular signal regulated protein kinase by neuropeptide Y and pancreatic polypeptide in CHO cells expressing the NPY Y(1), Y(2), Y(4) and Y(5) receptor subtypes.

Neuropeptide Y (NPY), 36-amino acid amidated peptide expressed in central and peripheral neurons, regulates a variety of physiological activities, including food intake, energy expenditure, vasoconstriction, anxiolysis, nociception and ethanol consumption. NPY binds to a family of G-protein coupled receptors whose activation results in inhibition of adenylyl cyclase activity. To more fully characterize the signal transduction pathways utilized by the NPY receptor subtypes, the pathways leading to phosphorylation of the extracellular signal regulated protein kinases 1 and 2 (ERK) have been compared in CHO cells expressing each of the four cloned human NPY receptor subtypes, Y(1), Y(2), Y(4) and Y(5). NPY Y(1), Y(2), Y(4) and Y(5) receptor-mediated ERK phosphorylation was blocked by pertussis toxin (PTX) exposure, indicating that all four receptors are coupled to inhibitory G(i/o) proteins. Exposure to the protein kinase C (PKC) inhibitor GF109203X diminished Y(1), Y(2) and Y(4) receptor-mediated ERK phosphorylation but completely blocked Y(5) receptor-mediated ERK phosphorylation. Additionally, Y(5) receptor-mediated ERK phosphorylation was inhibited by the phosphatidylinositol 3-kinase inhibitors LY294002 and wortmannin to a greater extent than was Y(1)-mediated ERK phosphorylation. These results demonstrate that in CHO cells, the Y(5) receptor and the Y(1), Y(2) and Y(4) receptors utilize different pathways to activate ERK.

Adenylate Cyclase Toxin↗

PubMed2002

A robust DNA mechanical device controlled by hybridization topology.

Controlled mechanical movement in molecular-scale devices has been realized in a variety of systems-catenanes and rotaxanes, chiroptical molecular switches, molecular ratchets and DNA-by exploiting conformational changes triggered by changes in redox potential or temperature, reversible binding of small molecules or ions, or irradiation. The incorporation of such devices into arrays could in principle lead to complex structural states suitable for nanorobotic applications, provided that individual devices can be addressed separately. But because the triggers commonly used tend to act equally on all the devices that are present, they will need to be localized very tightly. This could be readily achieved with devices that are controlled individually by separate and device-specific reagents. A trigger mechanism that allows such specific control is the reversible binding of DNA strands, thereby 'fuelling' conformational changes in a DNA machine. Here we improve upon the initial prototype system that uses this mechanism but generates by-products, by demonstrating a robust sequence-dependent rotary DNA device operating in a four-step cycle. We show that DNA strands control and fuel our device cycle by inducing the interconversion between two robust topological motifs, paranemic crossover (PX) DNA and its topoisomer JX2 DNA, in which one strand end is rotated relative to the other by 180 degrees. We expect that a wide range of analogous yet distinct rotary devices can be created by changing the control strands and the device sequences to which they bind.

Base Pairing↗

PubMed2002

Development and application of an isolated perfused rat liver model to study the stimulation and inhibition of tumor necrosis factor-alpha production ex vivo.

PURPOSE: To develop an isolated perfused rat liver (IPRL) model with low baseline levels of tumor necrosis factor (TNF)-alpha in the outlet perfusate to study the effects of immunostimulants and immunosuppressants on the release of TNF-alpha from this organ. METHODS: Isolated rat livers were perfused with a buffer containing no albumin or three different bovine serum albumin (BSA) preparations. Using the no-albumin perfusate, the inhibitory effects of methylprednisolone (MP) on lipopolysaccharide (LPS)-stimulated release of TNF-alpha were studied in livers isolated 1 or 5 h after the intravenous administration (5 mg/kg) of MP. The concentrations of TNF-a in the outlet perfusates were measured using enzyme-linked immunosorbent assay. RESULTS: In the absence of albumin, the perfusate levels of TNF-alpha were close to zero. However, when the perfusate contained BSA. the TNF-alpha levels in the perfusate reached as high as 1200 pg/ml at steady state. An injection of LPS into IPRLs perfused with a no-albumin perfusate resulted in mean (+/- SD) TNF-alpha steady-state concentrations of 825 +/- 125 pg/ml. The pretreatment of rats with MP before liver harvest attenuated the LPS-induced TNF-alpha release in the livers. However, the attenuation was substantial (>60%) and was statistically significant only 5 h after pretreatment with MP. CONCLUSIONS: Perfusates containing BSA may result in nonphysiologically high levels of TNF-alpha. An IPRL with a no-albumin perfusate is more suitable for studies of the stimulation and inhibition of TNF-alpha production by this organ.

Adjuvants, Immunologic↗

PubMed2002

Pharmacokinetics of plasma enfuvirtide after subcutaneous administration to patients with human immunodeficiency virus: Inverse Gaussian density absorption and 2-compartment disposition.

OBJECTIVE: Enfuvirtide (T-20) is the first of a novel class of human immunodeficiency virus (HIV) drugs that block gp41-mediated viral fusion to host cells. The objectives of this study were to develop a structural pharmacokinetic model that would adequately characterize the absorption and disposition of enfuvirtide pharmacokinetics after both intravenous and subcutaneous administration and to evaluate the dose proportionality of enfuvirtide pharmacokinetic parameters at a subcutaneous dose higher than that currently used in phase III studies. METHODS: Twelve patients with HIV infection received 4 single doses of enfuvirtide separated by a 1-week washout period in an open-label, randomized, 4-way crossover fashion. The doses studied were 90 mg (intravenous) and 45 mg, 90 mg, and 180 mg (subcutaneous). Serial blood samples were collected up to 48 hours after each dose. Plasma enfuvirtide concentrations were measured with use of a validated liquid chromatography-tandem mass spectrometry method. RESULTS: Enfuvirtide plasma concentration-time data after subcutaneous administration were well described by an inverse Gaussian density function-input model linked to a 2-compartment open distribution model with first-order elimination from the central compartment. The model-derived mean pharmacokinetic parameters (+/-SD) were volume of distribution of the central compartment (3.8 +/- 0.8 L), volume of distribution of the peripheral compartment (1.7 +/- 0.6 L), total clearance (1.44 +/- 0.30 L/h), intercompartmental distribution (2.3 +/- 1.1 L/h), bioavailability (89% +/- 11%), and mean absorption time (7.26 hours, 8.65 hours, and 9.79 hours for the 45-mg, 90-mg, and 180-mg dose groups, respectively). The terminal half-life increased from 3.46 to 4.35 hours for the subcutaneous dose range from 45 to 180 mg. CONCLUSIONS: An inverse Gaussian density function-input model linked to a 2-compartment open distribution model with first-order elimination from the central compartment was appropriate to describe complex absorption and disposition kinetics of enfuvirtide plasma concentration-time data after subcutaneous administration to patients with HIV infection. Enfuvirtide was nearly completely absorbed from subcutaneous depot, and pharmacokinetic parameters were linear up to a dose of 180 mg in this study.

Absorption↗

PubMed2002

GIS prediction model of malaria transmission in Jiangsu province.

OBJECTIVES: To perform GIS spatial analysis on malaria transmission patterns in Jiangsu after setting up a malaria database and developing GIS model of malaria transmission in Jiangsu province. METHODS: The epidemiological GIS database of malaria in Jiangsu province was established using ArcView 3.0a software. The climate data covering Jiangsu province and its peripheral area were extracted from the FAOCLIM database, the total growing degree days (TGDD) for Plasmodium vivax were calculated, and spatial distribution for TGDD was analyzed by ArcVeiw 3.0a. RESULTS: The predicted malaria distribution map based on TGDD was created, which showed that the transmission of malaria decreased gradually from west to east, which can be divided into three belts according to the degree of transmission. The 14-year mean morbidity distribution map of malaria in Jiangsu showed that the middle and west parts of Jiangsu is the most serious endemic area. The morbidity in the areas along the Taihu valley, such as Suzhou, Wuxi and Changzhou, as well as Nantong and a few of northern counties are the lowest. The morbidity of other places is at the middle level. The 14-year mean morbidity distribution map of malaria is correlated with predicted malaria distribution map for TGDD. CONCLUSION: It is possible to monitor the malaria transmission by GIS predicted model based on TGDD.

China↗

PubMed2002

[Detection of human herpes virus 8 in Kaposi sarcoma using polymerase chain reaction and single stranded probe in situ hybridization with a tyramide signal amplification system].

OBJECTIVE: To study the relationship between Kaposi's sarcoma (KS) and human herpes virus 8 (HHV8; Kaposi's sarcoma-associated herpes virus), and to develop an in situ hybridization (ISH) technique effective for clinical pathological diagnosis. METHODS: Polymerase chain reaction (PCR) technique was used to synthesize a digoxigenin-labeled single stranded DNA probe specific for HHV8 open reading frame 72 cyclin D homolog gene encoded mRNA as the probe accompanying with a tyramide signal amplification system (TSA) for ISH assay. Totally 20 formalin-fixed and paraffin-embedded samples from 14 cases of KS from Danish patients were collected for HHV8 detection. In order to compare the result obtained, all of these cases were checked simultaneously using PCR technique. RESULTS: HHV8 was detected in 10 of 14 (71%) KS cases, of which 8 cases were positive for HHV8 by both ISH and PCR. In ISH, HHV8 hybridization signal was seen as a dot or patch located in the nuclei of both the neoplastic spindle cells and the endothelial cells. HHV8 was found in lesions in all the stages of KS including early patch, plaque and late nodular or tumor lesions, as well as in the primary and metastatic lesions. All the control cases showed a relevant positive or negative results. CONCLUSIONS: The results further confirmed that there is a strong association between Kaposi's sarcoma and HHV8. The ISH technique with single stranded probe and TSA would be helpful in clinical pathological diagnosis for HHV8 infected diseases, such as KS, primary effusion lymphoma and multicentric Castleman's disease.

Adolescent↗

PubMedDate not supplied

Quantitative assessment of the cell penetrating properties of RI-Tat-9: evidence for a cell type-specific barrier at the plasma membrane of epithelial cells.

Penetration of epithelial cells represents the rate-determining step for the absorption of many drugs and pharmaceutical macromolecules such as proteins and nucleic acid therapeutics. While the potential of using cell-penetrating peptides (CPPs) to facilitate absorption has been increasingly recognized, the mechanism of cell penetration and the uptake into certain cells have recently been called into question due to methodological artifacts. Therefore, the objective of this study was to quantitatively assess the ability of RI-Tat-9, a proteolytically stable CPP, to penetrate epithelial cell monolayers. The permeability of RI-Tat-9 with two epithelial cell lines, Madin-Darby canine kidney (MDCK) and Caco-2 cells, was comparable to the leakiness of the respective intact monolayers. Microscopic imaging showed that fluorescence-tagged RI-Tat-9 did not enter these cells, further supporting a paracellular transport mechanism. Although insufficient data were generated in these studies to generalize the observed phenomenon, the entry of RI-Tat-9 into nonepithelial T lymphocytic MT2 cells, possibly by endocytosis, suggested that a cell type-specific barrier might exist that controlled uptake of RI-Tat-9 by cells. Compared to that in MT2 and HeLa cells, the active uptake of the peptide into MDCK monolayers was much slower and showed no dependence of cell energy. Furthermore, the equilibrium binding of RI-Tat-9 to MDCK cells at 0 degrees C was indicative of an interaction with a nonspecific receptor. A correlation between binding density and concentration difference across a leaky separation barrier suggested that repulsion of free peptide molecules by bound peptide molecules at the MDCK monolayer surface may be significant at micromolar concentrations. The results of this study quantitatively show that Tat CPP uptake into two commonly used epithelial cell types is minimal and possibly cell type-specific. Implications for Tat CPP-assisted drug delivery are discussed.

Animals↗

PubMedDate not supplied

Renal tubular epithelial expression of the coinhibitory molecule B7-DC (programmed death-1 ligand).

BACKGROUND: Renal tubular epithelial cells (TECs) function as antigen-presenting cells because they constitutively express MHC class II molecules and have the ability to present peptide antigen to CD4+T cells. However, the costimulatory signals provided by TECs for optimal T-cell activation have not been fully characterized. Increasing recognition of the importance of B7 dendritic cells (B7-DC) in immunoregulation raises the question of whether B7-DC is expressed on TECs and is involved in regulating TEC function. METHODS: B7-DC on cultured human and murine TECs was detected by flow cytometry in vitro. Immunohistochemistry was performed on human kidney biopsies. Coculture experiments were performed to confirm the role of TEC-related B7-DC in regulating CD4+T-cell activation. RESULTS: Data revealed that B7-DC is specifically expressed on TECs with inflammatory factor induced and diseased human kidney samples, including chronic glomerulonephritis, lupus nephritis, tubulointerstitial nephritis and renal cell carcinoma. B7-DC was a strong inhibitor of CD4+T-cell activation, as assessed by increased cytokine (interferon-gamma and interleukin-2) production and enhanced levels of T-cell activation marker CD69 in the presence of its blocking antibody. Blocking B7-DC/PD-1 enhanced antigen presentation. B7-DC is especially well expressed on TECs of diseased kidney samples and significantly down-regulates T-cell activation. CONCLUSIONS: We speculate that B7-DC might play an important role in maintaining peripheral tolerance, and in protecting the epithelium from immune-mediated tubulointerstitial injury.

Animals↗