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Biomedical subjects

Z G Wang

Publications and source records attributed to Z G Wang.

At least 19 recordsLinked to original sources
PubMed2006

Adiabatic shear failure and dynamic stored energy of cold work.

Dynamic testing of statically predeformed specimens of magnesium (AM50) shows that the failure strain increases with the level of prestrain. Interrupted and other dynamic tests show that the temperature rise prior to localization has only a minor influence on adiabatic shear band (ASB) formation. For all the tests, the dynamic deformation energy until ASB formation is found to be relatively constant, indicating that ASB is dependent almost solely on dynamic deformation processes, with quasistatic and thermal effects prior to localization being very marginal. We suggest the concept of a constant dynamic mechanical energy (toughness) as a quantitative criterion for ASB formation--this concept being related physically to the dynamic stored energy of cold work. All in all, the tests indicate that ASB failure is more dependent on energy considerations that on strain criteria, as has been considered until now.

Journal Article↗
PubMed2006

Primary leiomyosarcoma of the great saphenous vein: case report.

OBJECTIVE: To describe a case of primary leiomyosarcoma of the great saphenous vein. PATIENT RECORD: A 59-year-old Chinese lady presented with two painful lumps in the right thigh in the line of the great saphenous vein. At surgery, in September 2004, two tumors in the right great saphenous vein above the knee were excised with the intervening normal vein. Histopathological studies confirmed both masses as leiomyosarcoma. Radiotherapy was given postoperatively. The patient has been followed-up for 300 days after surgery with no evidence of local or distant metastasis. CONCLUSION: Leiomyosarcoma of the great saphenous vein can exist at more than one site. Tumor resection and radiotherapy was associated with good patient prognosis.

Female↗
PubMed2006

Gene expression profile of transgenic mouse kidney reveals pathogenesis of hepatitis B virus associated nephropathy.

Hepatitis B virus (HBV)-associated nephritis has been reported worldwide. Immune complex deposition has been accepted as its pathogenesis, although the association between the presence of local HBV DNA and viral antigen and the development of nephritis remains controversial. To understand better the roles played by HBV protein expression in the kidney, the global gene expression profile was studied in the kidney tissue of a lineage of HBV transgenic mouse (#59). The mice expressed HBsAg in serum, and HBsAg and HBcAg in liver and kidney, but without virus replication. Full-length HBV genome (adr subtype, C genotype) isolated from a chronic HBV carrier was used to establish the transgenic mice #59. Similarly manipulated mice that did not express HBV viral antigens served as controls. Southern blotting, hybridization with HBV probe, and immuno-histochemical staining were used to study HBV gene expression. mRNA extracted from the kidney tissue was analyzed using Affymetrix microarrays. HBsAg and HBcAg were located mainly in the cytoplasm of tubular epithelium. Altogether 520 genes were "up-regulated" more than twofold and 76 genes "down-regulated" more than twofold in the kidney. The complement activation, blood coagulation, and acute-phase response genes were markedly "up-regulated". Compared to the controls, the level of serum C3 protein was decreased in #59 mice, while the level of C3 protein from kidney extract was increased. Results indicate that expression of HBsAg and HBcAg in tubular epithelial cells of the kidney per se can up-regulate complement-mediated inflammatory gene pathways, in addition to immune complex formation.

Animals↗
PubMed2005

Quantum-dot growth simulation on periodic stress of substrate.

InAs quantum dots (QDs) are grown on the cleaved edge of an In(x)Ga(1-x)AsGaAs supperlattice experimentally and a good linear alignment of these QDs on the surface of an In(x)Ga(1-x)As layer has been realized. The modulation effects of periodic strain on the substrate are investigated theoretically using a kinetic Monte Carlo method. Our results show that a good alignment of QDs can be achieved when the strain energy reaches 2% of the atomic binding energy. The simulation results are in excellent qualitative agreement with our experiments.

Journal Article↗
PubMed2005

High-resolution imaging characterization of bladder dynamic morphophysiology by time-lapse optical coherence tomography.

We report an experimental study of the possibility of high-speed optical coherence tomography (OCT) for high-resolution imaging characterization of detrusor dynamic morphophysiology and analysis of the mechanisms that lead to geriatric incontinence (GI). The spontaneous contractility of intact fresh rabbit bladders was imaged with two-dimensional (2D) OCT ex vivo at up to 8 frames/s. The time-lapse 2D OCT images were postprocessed by image segmentation and fast-Fourier-transform analysis to characterize the dynamic morphological changes of the bladder contractility. In addition, we studied young and aging rat bladders to analyze the differences in dynamics. Preliminary results of our ex vivo study reveal that time-lapse OCT can track the contractile waves of bladders at high spatial resolution and characterize their dynamic morphophysiology in terms of amplitude, phase, and frequency. The results suggest that time-lapse OCT has the potential to act as a detrusor optical biopsy to enhance the diagnosis of detrusor dysfunction and thus of the mechanisms that lead to GI.

Algorithms↗
PubMed2005

Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model.

PURPOSE: We describe the technique of fluorescence image guided optical coherence tomography (FG-OCT). We examined its ability to enhance specificity and sensitivity for the noninvasive diagnosis of early bladder cancer. MATERIALS AND METHODS: Transitional cell carcinoma was developed in 54 Fisher 344 female rats by intravesical methyl-nitroso-urea instillations. Two or three rats were diagnosed sequentially by 5-ALA (5-aminolevulinic acid hydrochloride) induced fluorescence imaging, cross-sectional OCT and histological microscopy weekly during weeks 11 to 33 following initial methyl-nitroso-urea instillation to track the course of carcinogenesis. RESULTS: The specificity of fluorescence detection was significantly enhanced by FG-OCT (53% and 93%, respectively, p <0.0001). The sensitivity of fluorescence detection and FG-OCT was 79% and 100%, respectively. CONCLUSIONS: FG-OCT cystoscopy has the potential to diagnose early bladder cancer with high sensitivity and specificity with drastically decreased imaging time compared to that of white light guided OCT cystoscopy.

Adipose Tissue↗
PubMed2003

Analysis of microcystins in cyanobacteria blooms and surface water samples from Meiliang Bay, Taihu Lake, China.

Taihu Lake is the third largest freshwater lake in China. In recent years, the water pollution of cyanobacteria blooms has become a severe problem in this area. Microcystins (MCs) are an important group of toxic compounds mainly produced by some cyanobacteria species and have both acute and chronic hepatotoxic effects on animals and humans. This paper presents the first data on the identification and detection of MCs in both natural occurring cyanobacteria blooms and surface water samples (0-0.5 m), collected from Meiliang Bay, Taihu Lake, China. A conventional method for extraction and isolation of MCs from cyanobacteria blooms was applied. High-performance liquid chromatography (HPLC) analysis showed that the main toxic component in the cyanobacteria materials was MC-LR. The monoclonal antibody (mAb) against MC-LR produced by hybridoma technique was employed for direct competitive ELISA to detect the concentrations of MCs in bloom and water samples collected in 2001. The results not only revealed the presence of MCs but also temporal variations of MCs levels of three sampling stations in Meiliang Bay in 1 year. It is obvious that the MC contents were relatively higher during warm months and related with the status of eutrophication. Our study indicates the threat associated with MCs in water body of Taihu Lake. To prevent the MCs potential hazard on public health in this area, some necessary measures of monitoring and control of growth of cyanobacteria are urgently needed.

Bacterial Toxins↗
PubMed2001

Free expansion of elastic filaments.

The dynamics of an elastic polymer filament undergoing contour length expansion is studied using computer simulation. The expansion occurs by development of transverse buckling waves that grow through a coarsening process. The growing buckles locally organize into a helical structure with a characteristic persistence length. The helical domain boundaries are eliminated from the relaxing structure by unwinding through the ends of the rod. The growth of the helical domains results in self-propulsive motion of the expanding rod, as one large helix spanning the entire chain relaxes during the late stages of the dynamics. Stability analyses and scaling arguments are provided to explain the simulation results.

Journal Article↗
PubMed2001

Arsenic trioxide, a therapeutic agent for APL.

Acute promyelocytic leukemia (APL) is an interesting model in cancer research, because it can respond to the differentiation/apoptosis induction therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)). Over the past 5 years, it has been well demonstrated that As(2)O(3) induces a high complete remission (CR) rate in both primary and relapsed APL patients (around 85 to 90%). The side effects are mild to moderate in relapsed patients, while severe hepatic lesions have been found in some primary cases. After CR obtained in relapsed patients, chemotherapy in combination with As(2)O(3) as post-remission therapy has given better survival than those treated with As(2)O(3) alone. The effect of As(2)O(3) has been shown to be related to the expression of APL-specific PML-RARalpha oncoprotein, and there is a synergistic effect between As(2)O(3) and ATRA in an APL mouse model. Cell biology studies have revealed that As(2)O(3) exerts dose-dependent dual effects on APL cells. Apoptosis is evident when cells are treated with 0.5 approximately 2.0 microM of As(2)O(3) while partial differentiation is observed using low concentrations (0.1 approximately 0.5 microM) of the drug. The apoptosis-inducing effect is associated with the collapse of mitochondrial transmembrane potentials in a thiol-dependent manner, whereas the mechanisms underlying APL cell differentiation induced by low dose arsenic remain to be explored. Interestingly, As(2)O(3) over a wide range of concentration (0.1 approximately 2.0 microM) induces degradation of a key leukemogenic protein, PML-RARalpha, as well as the wild-type PML, thus setting up a good example of targeting therapy for human cancers.

Animals↗
PubMed2001

Short- and intermediate-time behavior of the linear stress relaxation in semiflexible polymers.

The linear viscoelasticity of semiflexible polymers is studied through Brownian Dynamics simulations covering a broad range of chain stiffness and time scales. Our results agree with existing theoretical predictions in the flexible and stiff limits; however, we find that over a wide intermediate-time window spanning several decades, the stress relaxation is described by a single power law t(-alpha), with the exponent alpha apparently varying continuously from 1/2 for flexible chains, to 5/4 for stiff ones. Our study identifies the limits of validity of the t(-3/4) power law at short times predicted by recent theories. An additional regime is identified, the "ultrastiff" chains, where this behavior disappears. In the absence of Brownian motion, the purely mechanical stress relaxation produces a t(-3/4) power law for both short and intermediate times.

Journal Article↗
PubMed2001

Atp11p and Atp12p are assembly factors for the F(1)-ATPase in human mitochondria.

Atp11p and Atp12p were first described as proteins required for assembly of the F(1) component of the mitochondrial ATP synthase in Saccharomyces cerevisiae (Ackerman, S. H., and Tzagoloff, A. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 4986-4990). Here we report the isolation of the cDNAs and the characterization of the human genes for Atp11p and Atp12p and show that the human proteins function like their yeast counterparts. Human ATP11 spans 24 kilobase pairs in 9 exons and maps to 1p32.3-p33, while ATP12 contains > or =8 exons and localizes to 17p11.2. Both genes are broadly conserved in eukaryotes and are expressed in a wide range of tissues, which suggests that Atp11p and Atp12p are essential housekeeping proteins of human cells. The information reported herein will be useful in the evaluation of patients with ascertained deficiencies in the ATP synthase, in which the underlying biochemical defect is unknown and may reside in a protein that influences the assembly of the enzyme.

Amino Acid Sequence↗
PubMed2001

Computational method to reduce the search space for directed protein evolution.

We introduce a computational method to optimize the in vitro evolution of proteins. Simulating evolution with a simple model that statistically describes the fitness landscape, we find that beneficial mutations tend to occur at amino acid positions that are tolerant to substitutions, in the limit of small libraries and low mutation rates. We transform this observation into a design strategy by applying mean-field theory to a structure-based computational model to calculate each residue's structural tolerance. Thermostabilizing and activity-increasing mutations accumulated during the experimental directed evolution of subtilisin E and T4 lysozyme are strongly directed to sites identified by using this computational approach. This method can be used to predict positions where mutations are likely to lead to improvement of specific protein properties.

Bacteriophage T4↗
PubMed2001

A strategy for probing the autonomy of cross-domain stereochemical communication in glycoconjugates.

Glycoproteins contain carbohydrate and peptide sectors. As a model for studying whether there exists stereochemical "communication" between the two domains, we prepared two glycopeptides differing only in the absolute stereochemistry of the peptide domain (L-peptide vs D-peptide). High-field NMR spectroscopy revealed that there are distinct and measurable differences, indicating that the two domains are at some level interactive.

Carbohydrate Conformation↗
PubMed2001

Role of promyelocytic leukemia (PML) protein in tumor suppression.

The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor alpha (RARalpha) gene in the vast majority of acute promyelocytic leukemia (APL) patients as a consequence of chromosomal translocations. The PMLRARalpha oncoprotein is thought to antagonize the function of PML through its ability to heterodimerize with and delocalize PML from the nuclear body. In APL, this may be facilitated by the reduction to heterozygosity of the normal PML allele. To determine whether PML acts as a tumor suppressor in vivo and what the consequences of deregulated programmed cell death in leukemia and epithelial cancer pathogenesis are, we crossed PML(-/-) mice with human cathepsin G (hCG)-PMLRARalpha or mammary tumor virus (MMTV)/neu transgenic mice (TM), models of leukemia and breast cancer, respectively. The progressive reduction of the dose of PML resulted in a dramatic increase in the incidence of leukemia, and in an acceleration of leukemia onset in PMLRARalpha TM. By contrast, PML inactivation did not affect neu-induced tumorigenesis. In hemopoietic cells from PMLRARalpha TM, PML inactivation resulted in impaired response to differentiating agents such as RA and vitamin D3 as well as in a marked survival advantage upon proapoptotic stimuli. These results demonstrate that: (a) PML acts in vivo as a tumor suppressor by rendering the cells resistant to proapoptotic and differentiating stimuli; (b) PML haploinsufficiency and the functional impairment of PML by PMLRARalpha are critical events in APL pathogenesis; and (c) aberrant control of programmed cell death plays a differential role in solid tumor and leukemia pathogenesis.

Animals↗
PubMed2001

Computationally focusing the directed evolution of proteins.

Directed evolution has proven to be a successful strategy for the modification of enzyme properties. To date, the preferred experimental procedure has been to apply mutations or crossovers randomly throughout the gene. With the emergence of powerful computational methods, it has become possible to develop focused combinatorial searches, guided by computer algorithms. Here, we describe several computational methods that have emerged to aid the optimization of mutant libraries, the targeting of specific residues for mutagenesis, and the design of recombination experiments.

Algorithms↗
PubMed2001

Involvement of MAPK activation in bacterial endotoxin-inducible tissue factor upregulation in human monocytic THP-1 cells.

BACKGROUND: Monocytic tissue factor (mTF) hypercoagulation leading to thrombotic complications is commonly observed following sepsis. OBJECTIVE: We herein study the intracellular mechanism of mTF upregulation in human model monocytic THP-1 cells in response to bacterial endotoxin (lipopolysaccharide, LPS; Escherichia coli O111:B04), determining if mitogen-activated protein kinase (MAPK) activation is involved in the signaling. METHODS: We assessed mTF upregulation by its cell surface expression, protein synthesis, and functional activity based on flow cytometry, Western blotting analysis, and a single-stage clotting assay, respectively. RESULTS: A 3-h challenge with LPS (100 ng/ml) drastically induced mTF functional activity, accompanied by elevated surface mTF expression and synthesis. The suppression by genistein (G) of LPS-inducible mTF upregulation implied the involvement of protein tyrosine kinase activation in mTF upregulation. LPS activated MAPK, which was significantly depressed by G, SB 203580 (SB), and PD 98058 (PD). Interestingly, inclusion of SB and PD also markedly diminished LPS-inducible mTF upregulation. The parallelism between MAPK and mTF activities revealed the involvement of MAPK activation in such mTF upregulation. Based on the ability of SB and PD to respectively block LPS-inducible tyrosine phosphorylation of p38 MAPK and Erk1/2, it was evident that tyrosine phosphorylation of MAPKs is required for mediating LPS-inducible mTF synthesis and upregulation. Contrasting with the established prevention of mTF upregulation by these inhibitors, failure to offset the already LPS-induced mTF activity seemed to be consistent with the view that LPS readily activated MAPK responsible for mTF synthesis. CONCLUSION: Our data suggest that the tyrosine phosphorylation of MAPKs (p38 and Erk1/2) leading to their activation could be a prerequisite for LPS induction of mTF synthesis contributing to the upregulation of mTF-initiated extrinsic coagulation.

Cell Line↗