Biomedical subjects

Yang Zhang

Publications and source records attributed to Yang Zhang.

At least 73 records · Page 4Linked to original sources

PubMed2006

[Efficacy of gefitinib on advanced non-small cell lung cancer in expanded access program (EAP)].

BACKGROUND & OBJECTIVE: Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, and has been used in treating advanced non-small cell lung cancer (NSCLC). This study was to evaluate the efficacy of Gefitinib on advanced NSCLC, and observe adverse events. METHODS: An open labeled, expanded access program (EAP) was conducted. Pathologically confirmed advanced NSCLC patients who had progressed after systemic chemotherapy or was not suitable for systemic chemotherapy were eligible for this program. Gefitinib (250 mg) was orally administered daily till disease progression or intolerable adverse events developed. RESULTS: From Sep. 2002 to Mar. 2005, 120 patients were enrolled, and 103 of them were assessable for response. The objective response rate was 18.4% (19/103). The disease control rate was 51.5% (53/103). The median survival time was 6 months (0.5-33 months). Adverse events were generally mild (grade I or II), including skin rash (30.1%), dry skin (12.6%), and diarrhea (25.2%). Two (1.9%) patients developed grade III elevation of serum glutamate pyruvate transaminase (SGPT). No grade IV adverse event occurred. CONCLUSION: Gefitinib is effective in treating advanced NSCLC, and the adverse events are mild.

Adenocarcinoma↗

PubMed2005

Effects of Ag doping on the photoluminescence of ZnO films grown on Si substrates.

Silver (Ag) doped and undoped ZnO films were grown on Si (100) substrates by the sol-gel process. Photoluminescence (PL) of two kinds of samples as a function of the excitation intensity has been measured, and PL intensities have been fitted by a power law. It is found that Ag doping increases the intensity of free emission from ZnO and does not change the position and the full width at half-maximum of the free exciton emission. In PL spectra of two kinds of samples under various excitation powers, no visible emission bands related to the deep levels were observed. These results reveal that doped Ag in ZnO films only enhances emission efficiency from free exciton recombination, not giving rise to new emissions.

Journal Article↗

PubMed2005

[Follow-up study in endovascular therapy for the renal artery stenosis].

OBJECTIVE: To evaluate the safety and efficacy of endovascular therapy for renal artery stenosis. METHODS: Percutaneous transluminal renal angioplasty with stent (PTRAS) was performed on 33 consecutive patients with severe renal artery stenosis who suffered from poorly controlled hypertension or renal dysfunction. They were subsequently underwent 7 to 49 months clinical follow up for the effect of the procedure on renal function, blood pressure control, mortality. RESULTS: Angiographic success was obtained in 32 (97.0%) of the 33 patients. The mortality was 18.2%. After PTRAS, two (6.1%) died of myocardial infarction within 4 months. Four (12.1%) patients with preoperative serum creatinine (Scr) > or = 177 micromol/L died of uraemia within 17 approximately 28 months. Twelve and twenty-four months after the procedure, systolic and diastolic blood pressure of 26 (78.8%) cases with preoperative Scr < 177 micromol/L significantly decreased (P < 0.05), with less antihypertensive medications taken and satisfactory renal function. CONCLUSION: For patients without serious cardiorenal disease, PTRAS has a beneficial effect on blood pressure and renal function. For patients with serious cardiorenal disease or preoperative Scr > or = 177 micromol/L, the mortality is higher. PTRAS should be performed prudently. The preservation of renal function may be enhance by using renal protection device.

Adolescent↗

PubMed2005

Human Yip1A specifies the localization of Yif1 to the Golgi apparatus.

Yip1p and Yif1p are essential for transport from ER to Golgi stack during the early secretory pathway in budding yeast. Here, we report the identification and characterization of human Yif1. Sequence analysis revealed that human Yif1 (HsYif1), like most of the other YIP1 protein family members, contains multiple transmembrane segments. Double immunofluorescence study revealed co-distribution of HsYif1 with Golgi marker such as GS27. To delineate the function of HsYif1, we conducted a yeast two-hybrid assay and identified an interaction between human HsYif1 and HsYip1A, a homolog of yeast Yip1. In addition, our immunoprecipitation pull-down assay validates the interaction between HsYif1 and HsYip1A. Moreover, our immunofluorescence study demonstrates the co-distribution of HsYif1 and HsYip1A. Significantly, over-expression of mutant HsYip1A-lacked cytosolic region disrupts the localization of HsYif1 to the Golgi, suggesting that HsYip1A specifies the localization of HsYif1 to the Golgi. Therefore, we conclude that human Yip1A interacts with and determines the localization of HsYif1 to the Golgi apparatus.

Amino Acid Sequence↗

PubMed2005

Dielectric constant and density dependence of the structure of supercritical carbon dioxide using a new modified empirical potential model: a Monte Carlo simulation study.

Two modified versions of the Elementary Physical Model (EPM) [J. Phys. Chem. 1995, 99, 12021] for supercritical carbon dioxide have been proposed in this work and their validities are affirmed by computing the thermodynamic properties and dielectric constant up to 910 kg/m3 with use of canonical ensemble Monte Carlo simulation. Simulations performed for 500 molecules with the EPM2-M model reproduce the experimental data accurately at all thermodynamic states. The structural analyses demonstrate that the aggregation is strong at low density while the coordination number is large at high density. In addition, a detailed study on the radial and angular correlation functions reveals that the T-shaped geometry is dominate while a variety of other structures still appear in the first coordination shell. Furthermore, the angular correlation functions show that the probability of a molecule being oriented toward the convex side of another molecule is equal to that pointing toward the concave side since the molecular nonlinearity of carbon dioxide is only marginal. As the distance between two molecules increases, the preferred orientations disappear quickly and all the results are in good agreement with the prior ab initio calculation [J. Chem. Phys. 2004, 120, 9694].

Journal Article↗

PubMed2005

The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilate.

3-Hydroxyanthranilate-3,4-dioxygenase (HAD) is a non-heme Fe(II) dependent enzyme that catalyzes the oxidative ring-opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconic semialdehyde. The enzymatic product subsequently cyclizes to quinolinate, an intermediate in the biosynthesis of nicotinamide adenine dinucleotide. Quinolinate has also been implicated in important neurological disorders. Here, we describe the mechanism by which 4-chloro-3-hydroxyanthranilate inhibits the HAD catalyzed reaction. Using overexpressed and purified bacterial HAD, we demonstrate that 4-chloro-3-hydroxyanthranilate functions as a mechanism-based inactivating agent. The inactivation results in the consumption of 2 +/- 0.8 equiv of oxygen and the production of superoxide. EPR analysis of the inactivation reaction demonstrated that the inhibitor stimulated the oxidation of the active site Fe(II) to the catalytically inactive Fe(III) oxidation state. The inactivated enzyme can be reactivated by treatment with DTT and Fe(II). High resolution ESI-FTMS analysis of the inactivated enzyme demonstrated that the inhibitor did not form an adduct with the enzyme and that four conserved cysteines were oxidized to two disulfides (Cys125-Cys128 and Cys162-Cys165) during the inactivation reaction. These results are consistent with a mechanism in which the enzyme, complexed to the inhibitor and O2, generates superoxide which subsequently dissociates, leaving the inhibitor and the oxidized iron center at the active site.

3-Hydroxyanthranilate 3,4-Dioxygenase↗

PubMed2005

Structural studies on 3-hydroxyanthranilate-3,4-dioxygenase: the catalytic mechanism of a complex oxidation involved in NAD biosynthesis.

3-Hydroxyanthranilate-3,4-dioxygenase (HAD) catalyzes the oxidative ring opening of 3-hydroxyanthranilate in the final enzymatic step of the biosynthetic pathway from tryptophan to quinolinate, the universal de novo precursor to the pyridine ring of nicotinamide adenine dinucleotide. The enzyme requires Fe2+ as a cofactor and is inactivated by 4-chloro-3-hydroxyanthranilate. HAD from Ralstonia metallidurans was crystallized, and the structure was determined at 1.9 A resolution. The structures of HAD complexed with the inhibitor 4-chloro-3-hydroxyanthranilic acid and either molecular oxygen or nitric oxide were determined at 2.0 A resolution, and the structure of HAD complexed with 3-hydroxyanthranilate was determined at 3.2 A resolution. HAD is a homodimer with a subunit topology that is characteristic of the cupin barrel fold. Each monomer contains two iron binding sites. The catalytic iron is buried deep inside the beta-barrel with His51, Glu57, and His95 serving as ligands. The other iron site forms an FeS4 center close to the solvent surface in which the sulfur atoms are provided by Cys125, Cys128, Cys162, and Cys165. The two iron sites are separated by 24 A. On the basis of the crystal structures of HAD, mutagenesis studies were carried out in order to elucidate the enzyme mechanism. In addition, a new mechanism for the enzyme inactivation by 4-chloro-3-hydroxyanthranilate is proposed.

3-Hydroxyanthranilate 3,4-Dioxygenase↗

PubMed2005

Fabrication of calcium sulfate/PLLA composite for bone repair.

The bone-repairing composite material CS/PLLA was fabricated by mixing poly-L-lactic acid (PLLA) and calcium sulfate hemihydrate (CSH). The structure of the composite was analyzed with Infrared spectroscope, X-ray diffraction, and scanning electron microscope. The results indicated that the crystal pattern of calcium sulfate was affected by the addition of PLLA. PLLA part impacted the development of calcium sulfate dihydrate (CSD) crystal by slowing the conversion from CSH to CSD, so the composites are actually composed of CSH, CSD, and PLLA. The absorbing test in vitro showed that CS/PLLA composite absorbed more slowly than pure CS, suggesting the addition of PLLA can adjust the absorption rate of CS to meet different requirements. The pH value changes of the media had similar trends for different composites during the absorbing test of CS/PLLA samples in aqueous medium, which was connected to the absorption of calcium sulfate. The absorption of calcium sulfate in a certain time left a porous PLLA scaffold that will enable cells to further grow in. The surface of CS/PLLA pellets was inoculated with human osteoblasts, and the primary results showed that the osteoblasts could attach and spread on the surface, which will stimulate our desire for further study.

Bone Substitutes↗

PubMed2005

TM-align: a protein structure alignment algorithm based on the TM-score.

We have developed TM-align, a new algorithm to identify the best structural alignment between protein pairs that combines the TM-score rotation matrix and Dynamic Programming (DP). The algorithm is approximately 4 times faster than CE and 20 times faster than DALI and SAL. On average, the resulting structure alignments have higher accuracy and coverage than those provided by these most often-used methods. TM-align is applied to an all-against-all structure comparison of 10 515 representative protein chains from the Protein Data Bank (PDB) with a sequence identity cutoff <95%: 1996 distinct folds are found when a TM-score threshold of 0.5 is used. We also use TM-align to match the models predicted by TASSER for solved non-homologous proteins in PDB. For both folded and misfolded models, TM-align can almost always find close structural analogs, with an average root mean square deviation, RMSD, of 3 A and 87% alignment coverage. Nevertheless, there exists a significant correlation between the correctness of the predicted structure and the structural similarity of the model to the other proteins in the PDB. This correlation could be used to assist in model selection in blind protein structure predictions. The TM-align program is freely downloadable at http://bioinformatics.buffalo.edu/TM-align.

Algorithms↗

PubMed2005

Effects of language experience: neural commitment to language-specific auditory patterns.

Linguistic experience alters an individual's perception of speech. We here provide evidence of the effects of language experience at the neural level from two magnetoencephalography (MEG) studies that compare adult American and Japanese listeners' phonetic processing. The experimental stimuli were American English /ra/ and /la/ syllables, phonemic in English but not in Japanese. In Experiment 1, the control stimuli were /ba/ and /wa/ syllables, phonemic in both languages; in Experiment 2, they were non-speech replicas of /ra/ and /la/. The behavioral and neuromagnetic results showed that Japanese listeners were less sensitive to the phonemic /r-l/ difference than American listeners. Furthermore, processing non-native speech sounds recruited significantly greater brain resources in both hemispheres and required a significantly longer period of brain activation in two regions, the superior temporal area and the inferior parietal area. The control stimuli showed no significant differences except that the duration effect in the superior temporal cortex also applied to the non-speech replicas. We argue that early exposure to a particular language produces a "neural commitment" to the acoustic properties of that language and that this neural commitment interferes with foreign language processing, making it less efficient.

Acoustic Stimulation↗

PubMed2005

Preliminary investigation of the three-dimensional structure of Salmonella typhimurium uridine phosphorylase in the crystalline state.

Uridine phosphorylase (UPh) catalyzes the phosphorolytic cleavage of the C-N glycosidic bond of uridine to ribose 1-phosphate and uracil in the pyrimidine-salvage pathway. The crystal structure of the Salmonella typhimurium uridine phosphorylase (StUPh) has been determined at 2.5 A resolution and refined to an R factor of 22.1% and an Rfree of 27.9%. The hexameric StUPh displays 32 point-group symmetry and utilizes both twofold and threefold non-crystallographic axes. A phosphate is bound at the active site and forms hydrogen bonds to Arg91, Arg30, Thr94 and Gly26 of one monomer and Arg48 of an adjacent monomer. The hexameric StUPh model reveals a close structural relationship to Escherichia coli uridine phosphorylase (EcUPh).

Binding Sites↗

PubMed2005

Function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome coronavirus.

To identify the function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome (SARS) coronavirus (CoV), we analyzed the protein-protein interaction among HAb18G/CD147, cyclophilin A (CyPA), and SARS-CoV structural proteins by coimmunoprecipitation and surface plasmon resonance analysis. Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147. Further research showed that HAb18G/CD147, a transmembrane molecule, was highly expressed on 293 cells and that CyPA was integrated with SARS-CoV. HAb18G/CD147-antagonistic peptide (AP)-9, an AP of HAb18G/CD147, had a high rate of binding to 293 cells and an inhibitory effect on SARS-CoV. These results show that HAb18G/CD147, mediated by CyPA bound to SARS-CoV N protein, plays a functional role in facilitating invasion of host cells by SARS-CoV. Our findings provide some evidence for the cytologic mechanism of invasion by SARS-CoV and provide a molecular basis for screening anti-SARS drugs.

Antigens, CD↗

PubMed2005

Hierarchical chain model of spider capture silk elasticity.

Spider capture silk is a biomaterial with both high strength and high elasticity, but the structural design principle underlying these remarkable properties is still unknown. It was revealed recently by atomic force microscopy that an exponential force-extension relationship holds both for capture silk mesostructures and for intact capture silk fibers [N. Becker et al., Nat. Mater. 2, 278 (2003)]]. In this Letter a simple hierarchical chain model was proposed to understand and reproduce this striking observation. In the hierarchical chain model, a polymer is composed of many structural motifs which organize into structural modules and supramodules in a hierarchical manner. Each module in this hierarchy has its own characteristic force. The repetitive patterns in the amino-acid sequence of the major flagelliform protein of spider capture silk is in support of this model.

Animals↗

PubMed2005

The protein structure prediction problem could be solved using the current PDB library.

For single-domain proteins, we examine the completeness of the structures in the current Protein Data Bank (PDB) library for use in full-length model construction of unknown sequences. To address this issue, we employ a comprehensive benchmark set of 1,489 medium-size proteins that cover the PDB at the level of 35% sequence identity and identify templates by structure alignment. With homologous proteins excluded, we can always find similar folds to native with an average rms deviation (RMSD) from native of 2.5 A with approximately 82% alignment coverage. These template structures often contain a significant number of insertions/deletions. The tasser algorithm was applied to build full-length models, where continuous fragments are excised from the top-scoring templates and reassembled under the guide of an optimized force field, which includes consensus restraints taken from the templates and knowledge-based statistical potentials. For almost all targets (except for 2/1,489), the resultant full-length models have an RMSD to native below 6 A (97% of them below 4 A). On average, the RMSD of full-length models is 2.25 A, with aligned regions improved from 2.5 A to 1.88 A, comparable with the accuracy of low-resolution experimental structures. Furthermore, starting from state-of-the-art structural alignments, we demonstrate a methodology that can consistently bring template-based alignments closer to native. These results are highly suggestive that the protein-folding problem can in principle be solved based on the current PDB library by developing efficient fold recognition algorithms that can recover such initial alignments.

Algorithms↗

PubMed2005

TASSER: an automated method for the prediction of protein tertiary structures in CASP6.

The recently developed TASSER (Threading/ASSembly/Refinement) method is applied to predict the tertiary structures of all CASP6 targets. TASSER is a hierarchical approach that consists of template identification by the threading program PROSPECTOR_3, followed by tertiary structure assembly via rearranging continuous template fragments. Assembly occurs using parallel hyperbolic Monte Carlo sampling under the guide of an optimized, reduced force field that includes knowledge-based statistical potentials and spatial restraints extracted from threading alignments. Models are automatically selected from the Monte Carlo trajectories in the low-temperature replicas using the clustering program SPICKER. For all 90 CASP targets/domains, PROSPECTOR_3 generates initial alignments with an average root-mean-square deviation (RMSD) to native of 8.4 A with 79% coverage. After TASSER reassembly, the average RMSD decreases to 5.4 A over the same aligned residues; the overall cumulative TM-score increases from 39.44 to 52.53. Despite significant improvements over the PROSPECTOR_3 template alignment observed in all target categories, the overall quality of the final models is essentially dictated by the quality of threading templates: The average TM-scores of TASSER models in the three categories are, respectively, 0.79 [comparative modeling (CM), 43 targets/domains], 0.47 [fold recognition (FR), 37 targets/domains], and 0.30 [new fold (NF), 10 targets/domains]. This highlights the need to develop novel (or improved) approaches to identify very distant targets as well as better NF algorithms.

Algorithms↗

PubMed2005

Two ancient rounds of polyploidy in rice genome.

An ancient genome duplication (PPP1) that predates divergence of the cereals has recently been recognized. We report here another potentially older large-scale duplication (PPP2) event that predates monocot-dicot divergence in the genome of rice (Oryza sativa L.), as inferred from the age distribution of pairs of duplicate genes based on recent genome data for rice. Our results suggest that paleopolyploidy was widespread and played an important role in the evolution of rice.

Biological Evolution↗

PubMed2005

PNP anticancer gene therapy.

Escherichia coli purine nucleoside phosphorylase (PNP) catalyzes the cleavage of 9-(2-deoxy-beta-D-ribofuranosyl)-6-methylpurine (MeP-dR), while human PNP does not. MeP-dR is well tolerated while the cleavage product, 6-methylpurine (MeP), is highly cytotoxic. This clinical profile suggests an anticancer gene therapy strategy in which solid tumors are transfected with the gene for E. coli PNP. Tumor cells expressing E. coli PNP will liberate MeP and be killed. Furthermore, MeP released from the cell via the purine transport system will enter nearby cells, resulting in bystander killing of tumor cells. To reduce toxicity resulting from activation of MeP-dR by intestinal tract flora, we redesigned the E. coli PNP active site to cleave prodrugs that are not cleaved by wild type E. coli PNP. It is possible that the variation of substrate specificity among enzymes that cleave nucleosides will have broader application in the gene therapy approach to prodrug activation. Here we review progress in the development of E. coli PNP anticancer gene therapy. We also review the structural basis for activity of nucleoside phosphorylases and suggest future directions for the development of activating enzymes for suicide gene therapy.

Cell Line, Tumor↗

PubMed2005

[A three-dimensional finite element analysis for the biomechanical characteristics of orthodontic anchorage micro-implant].

PURPOSE: To establish a three-dimensional finite element model for orthodontic anchorage micro-implant,and to analyze the influence of different titled angles on the biomechanical characteristics of orthodontic anchorage implant-bone interface. METHODS: ANSYS(Analysis System)finite element analysis software was used to perform the finite element modeling of the micro-implant with 7 different tilted angles, including 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees and 90 degrees. A simulated orthodontic force, which was 200 grams, was loaded mesiodistally to the mathematical models. The stress and displacement distribution on the implant-bone interface were analyzed. RESULTS: As the titled angle increased, the Von-Mises stress at the cervix of the implants were 1.0792, 1.0104, 0.8848, 0.8181, 0.7583, 0.6339 and 0.5608MPa, while the displacement were 5.5513, 4.9900, 3.7419, 3.1264, 2.5874, 1.3624 and 0.8027microm CONCLUSION: The micro-implant can be safely loaded with 200 grams of mesiodistal orthodontic force. The increase of the titled angle can efficaciously enhance the ability,implicating that the implant can bear a mesiodistal orthodontic force, vertical angle should be chosen when the micro-implant is embedded. Supported by Natural Science Foundation of Liaoning Province (20042076).

Biomechanical Phenomena↗