Biomedical subjects

Jia Xu

Publications and source records attributed to Jia Xu.

25 records · Page 2Linked to original sources

PubMed2004

Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.

Unintended inhibition of the cardiac potassium channel human ether-a-go-go-related gene (hERG) is considered the main culprit in drug-induced arrhythmias known as torsades de pointes. Electrophysiology is the most reliable in vitro screening method for identifying potential cardiac hERG liabilities, but only the recent advent of planar electrode-based voltage clamp electrophysiology promises sufficient throughput to support the drug testing needs of most drug discovery programs. We have assessed the reliability of this new format of the voltage clamp technology in measuring the activity of small molecules on the hERG channel. Based on the results herein of a screening against a panel of well-characterized hERG-active and -inactive molecules, we demonstrate that planar electrode electrophysiology, utilizing the Sealchip and PatchXpress technology platform (AVIVA Biosciences Corp., San Diego, CA), is comparable to traditional electrophysiology based on glass micropipettes in its reliability and data content. The new technology will allow significantly higher throughput and more thorough testing of pharmaceutical compounds.

Amiodarone↗

PubMed2004

[Study on releasing rate of chrysophanol from Ruyi Jinhuang plaster].

OBJECTIVE: To study the releasing rate of chrysophanol from Ruyi Jinhuang plaster. METHOD: Based on the detecting methods of releasing rate and residual dosage applied in (Pharmacopoeia of P. R. C) (2000 edition), the contents of chrysophanol were detected by HPLC. RESULT: Chrysophanol in Ruyi Jinhuang plaster could well be released from plaster and to form medicinal concentration gradient. CONCLUSION: Chrysophanol in Ruyi-Jinhuang plaster can possibly be absorbed by skin.

Administration, Cutaneous↗

PubMed2003

THY1 expression is associated with tumor suppression of human ovarian cancer.

Microcell-mediated transfer of chromosome 11 into the human ovarian cancer cell line SKOV-3 results in suppression of tumorigenicity in severe combined immunodeficiency (SCID) mice. To identify the differentially expressed transcripts associated with suppression of tumorigenicity, cDNA populations from the slow-growing tumorigenic clone 11(H)8-3, tumorigenic clone 11(H)8-4, and parental SKOV-3 cells were subtracted from the nontumorigenic clones, 11(H)7-2 and 11(C)9-8. The subtracted cDNA populations were either cloned, sequenced and searched in GenBank, or analyzed by gene discovery array screening. A cDNA transcript corresponding to the THY1 gene located at chromosome 11q23 approximately q24 was found to be exclusively expressed in the two nontumorigenic cell clones. In contrast, THY1 expression was not detected in SKOV-3, the tumorigenic hybrid clones, or six other tumorigenic ovarian cancer cell lines. Further analysis using immunocytochemistry and quantitative flow cytometry with a Thy-1-specific antibody confirmed the exclusive expression of THY1 at the protein level in the two nontumorigenic clones. Several cell growth and differentiation-related genes, including thrombospondin 1 (THBS1), SPARC [secreted protein, acidic, cysteine-rich (osteonectin)], and fibronectin (FN1) were also found to be upregulated in the nontumorigenic clones; however, these were expressed in the slow-growing tumorigenic clones as well. Expression of these genes was not observed in the parental SKOV-3 cell line and therefore must be regulated by a gene or genes on chromosome 11. Our results suggest that THY1 is a putative tumor suppressor gene for ovarian cancer and that THBS1, SPARC, and FN1 are genes associated with the regulation of in vivo tumor growth rate.

Cell Division↗

PubMed2003

A benchmark study with sealchip planar patch-clamp technology.

Although conventional patch-clamp methods provide high information content, they are labor-intensive and suffer from low throughput and high overall cost. Several approaches for achieving high throughput electrophysiology are under development, among which microchip-based patch-clamp systems uniquely achieve a higher degree of miniaturization, faster perfusion and mixing, and lower reagent cost without losing information content. The goal of this study was to establish a benchmark for our biochip technology with 52 chips tested sequentially. We demonstrate that our microfabrication and processing technology is sufficiently mature to produce a consistent hole size. We further demonstrate high-quality planar whole-cell patch clamping with >75% overall success rate at achieving gigaohm seals, followed by stable whole-cell access lasting at least 15 min with access resistance (Ra) below 15 MOmega and membrane resistance (Rm) above 200 MOmega. These biochips are ideally suited for high throughput compound screening for ion channel targets.

Animals↗

PubMed2002

Phylogenetic analysis reveals that a dwarfing disease on different cereal crops in China is due to rice black streaked dwarf virus (RBSDV).

A viral disease with dwarfing symptoms is associated with severe damage of different cereal crops including rice, maize, wheat and sorghum grown in China. It is believed that the pathogenic agent of the disease on rice and sorghum is rice black streaked dwarf virus (RBSDV), however, the cause of maize dwarf disease in China is still inconclusive. In this report, dsRNA was isolated from virus particles obtained from the diseased plants of rice, maize, wheat and sorghum from two Chinese provinces. Full-length cDNAs of genome segments 9 (S9) and 10 (S 10) were obtained through a RT-PCR approach. Sequence analysis showed that the S9 sequences of Chinese isolates and Japanese RBSDV isolate were very similar to each other (89.1-89.6% identity at the nucleotide level, 92.3-92.9% and 95.8-98.6% identity at the amino acid level for ORF1 and ORF2, respectively). In addition, the S10 sequences of Chinese isolates and Japanese RBSDV were very similar to each other (93.0-95.4% identical nucleotides and 96.2-97.0% identical amino acids, respectively). However, there were lower similarities for S9 and S10 sequences between Chinese isolates and an Italian Maize Rough Dwarf Virus (MRDV) isolate. Phylogenetic analysis indicates that Chinese viral isolates found to infect rice, maize, wheat and sorghum and leading to similar cereal dwarfing manifestations could be grouped to the same virus species, RBSDV.

China↗

PubMed2001

Ion-channel assay technologies: quo vadis?

Although many existing methods are used to study the functions of ion channels and to screen lead compounds for important ion-channel targets, new technologies are being developed for improved performance. It is important to identify the advantages and disadvantages of each technology. In this review, we segment the ion-channel assay market according to distinguishable applications, and compare the needs of each market segment with the capabilities of different technologies in terms of multiple assay attributes. We further discuss the future directions in the development of ion-channel assays.

Journal Article↗

PubMedDate not supplied

Early gene activation in chronic leukemic B lymphocytes induced toward a plasma cell phenotype.

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of lymphocytes that are arrested at an intermediate stage of B lymphocyte development. CLL B lymphocytes transform (mature) to a plasmacytic phenotype with loss of CD19 and CD20 and the appearance of cytoplasmic immunoglobulin when treated in vitro with phorbol esters. We have used array hybridization technology to describe gene expression patterns for untreated and tetradecanoyl phorbol acetate (TPA)-treated CLL B cells at 5, 10, and 20 min following initial TPA exposure. Three genes, early growth response factor 1 (EGR-1), dual specificity phosphatase 2, and CD69 (early T-cell activation antigen), showed a 2.0-fold or greater increase in mRNA transcription at four or more of six time points in two studies. Upregulation of expression of these genes was confirmed by real-time polymerase chain reaction in the TPA-treated cells of four CLL patients. A progressive increase in gene expression was observed during the 20-min time course for all three genes. In addition, protein expression of EGR-1 and CD69 was increased as measured by immunofluorescence cell analysis. Several genes (PKC, n-myc, jun D, and BCL-2) previously reported as overexpressed in CLL lymphocytes were overexpressed in these studies also, but were not altered by TPA treatment. Genes for proteins whose upregulation requires hours of TPA exposure (the 4F2hc component of the L-system amino acid transporter, prohibition, and hsp60) were assessed, and their later expression contrasted with the early expression of EGR-1, dual specificity phosphatase 2, and CD69. EGR-1 encodes a zinc-finger transcription factor that is induced by pokeweed mitogen and TPA and promotes B lymphocyte maturation. The dual specificity phosphatase 2 encodes an enzyme that reverses mitogen activated protein kinase cell activation by dephosphorylation. The CD69 protein is induced by TPA in thymocytes and is a type II transmembrane signaling molecule in hematopoietic cells. These findings suggest that the products of these three genes may be central to early steps in the TPA-induced evolution of CLL B cells to a plasmacytic phenotype.

Antigens, CD↗