Biomedical subjects

Y D Wang

Publications and source records attributed to Y D Wang.

At least 19 recordsLinked to original sources

PubMed2006

Maxwell's demon assisted thermodynamic cycle in superconducting quantum circuits.

We study a new quantum heat engine (QHE), which is assisted by a Maxwell's demon. The QHE requires three steps: thermalization, quantum measurement, and quantum feedback controlled by the Maxwell demon. We derive the positive-work condition and operation efficiency of this composite QHE. Using controllable superconducting quantum circuits as an example, we show how to construct our QHE. The essential role of the demon is explicitly demonstrated in this macroscopic QHE.

Journal Article↗

PubMed2005

Cooling mechanism for a nanomechanical [corrected] resonator by periodic coupling to a Cooper pair box.

We propose and study an active cooling mechanism for the nanomechanical resonator (NAMR) based on periodical coupling to a Cooper pair box (CPB), which is implemented by a designed series of magnetic flux pluses threading through the CPB. When the initial phonon number of the NAMR is not too large, this cooling protocol is efficient in decreasing the phonon number by 2 to 3 orders of magnitude. Our proposal is theoretically universal in cooling various boson systems of a single mode. It can be specifically generalized to prepare the nonclassical state of the NAMR.

Journal Article↗

PubMed2004

Identification and characterisation of constitutional chromosome abnormalities using arrays of bacterial artificial chromosomes.

Constitutional chromosome deletions and duplications frequently predispose to the development of a wide variety of cancers. We have developed a microarray of 6000 bacterial artificial chromosomes for array-based comparative genomic hybridisation, which provides an average resolution of 750 kb across the human genome. Using these arrays, subtle gains and losses of chromosome regions can be detected in constitutional cells, following a single overnight hybridisation. In this report, we demonstrate the efficiency of this procedure in identifying constitutional deletions and duplications associated with predisposition to retinoblastoma, Wilms tumour and Beckwith-Wiedemann syndrome.

Bacteria↗

PubMed2003

In situ synchrotron study of phase transformation behaviors in bulk metallic glass by simultaneous diffraction and small angle scattering.

We have used a new approach involving simultaneous diffraction and small angle scattering to study the amorphous-to-crystalline phase transformation in Zr-based bulk metallic glass. In situ, time-resolved data provided the first direct demonstration of a phase separation prior to crystallization. There is evidence that nucleation and growth of the crystalline phase occur in separate stages, with different kinetics. Our data support the view that crystalline nucleation is achieved via short-range diffusion of small atoms (e.g., Ni), whereas the growth is dictated by long-range diffusion.

Journal Article↗

PubMed2001

Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity.

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC(50) = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of 1a led to 1c, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of 1c with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC(50) of 1.2 nM in the Src enzymatic assay, an IC(50) of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

Animals↗

PubMed2001

Characterization of neuronal cell death in normal and diabetic rats following exprimental focal cerebral ischemia.

We have studied the forms of cell death following ischemia/reperfusion, and the influence of diabetes mellitus (DM) as an additional factor. Based on the models of diabetes and middle cerebral artery occlusion (MCAO), characteristics of cell death after ischemia/reperfusion were evaluated synthetically by different methods: pathology, FCM, TUNEL and DNA agarose electrophoresis. The results showed that the occurrence of cerebral injury after ischemia/reperfusion was accompanied by cell necrosis and cell apoptosis. Cell apoptosis was mainly located in the ischemic penumbral (IP) zone around the densely ischemic focus. The ischemic core was characterized by cell necrosis. At the same time, the results showed that the process of ischemic cerebral injury worsened by DM was related to inducing cell apoptosis in IP and mid zone. In conclusion, there existed not only cell apoptosis but cell necrosis in brain damage following focal cerebral ischemia/reperfusion and showed a close, internal relationship between them. Brain damage following cerebral ischemia/reperfusion was worsened distinctly under diabetic conditions.

Animals↗

PubMed2001

Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3-quinolinecarbonitriles.

Screening of a directed compound library in a yeast-based assay identified 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (2a) as a Src inhibitor. An enzymatic assay established that 2a was an ATP-competitive inhibitor of the kinase activity of Src. We present here SAR data for 2a which shows that the aniline group at C-4, the carbonitrile group at C-3, and the alkoxy groups at C-6 and C-7 of the quinoline are crucial for optimal activity. Increasing the size of the C-2 substituent of the aniline at C-4 of 2a from chloro to bromo to iodo resulted in a corresponding increase in Src inhibition. Furthermore, replacement of the 7-methoxy group of 2a with various 3-heteroalkylaminopropoxy groups provided increased inhibition of both Src enzymatic and cellular activity. Compound 25, which contains a 3-morpholinopropoxy group, had an IC(50) of 3.8 nM in the Src enzymatic assay and an IC(50) of 940 nM for the inhibition of Src-dependent cell proliferation.

Aniline Compounds↗

PubMed2001

[Clinical observation on treatment of non-small cell lung cancer with Chinese herbal medicine combined with bronchial arterial infusion chemotherapy].

OBJECTIVE: To explore the effect of treatment for non-small cell lung cancer (NSCLC) with Chinese herbal medicine (CHM) combined with bronchial arterial infusion chemotherapy (BAIC). METHODS: Patients with moderate or advanced NSCLC were randomly divided into two groups, the 39 patients in the treated group treated with CHM plus BAIC therapy and 37 in the control group treated with BAIC alone. The short-term therapeutic effect, long-term survival rate, changes of clinical principal symptoms, quality of life and peripheral blood pictures in the two groups were observed and compared. RESULTS: After treatment the rate of CR + PR + NC in the treated and the control group was 92.31% and 70.27% respectively, the inter-group comparison showed a significant difference (P < 0.05). The 0.5-, 1- and 2-year survival rate in the treated group was 79.49%, 56.41% and 51.28% respectively and in the control group, 72.97%, 51.35% and 24.32% respectively. The 2-year survival rate in the former was better than that in the latter (P < 0.05). Moreover, the improvement of clinical symptoms, Karnofsky scoring, body weight and peripheral blood picture in the treated group was superior to that in the control group. CONCLUSION: Therapeutic effect of BAIC could be enhanced by combining it with CHM.

Adenocarcinoma↗

PubMed2000

Inhibitors of src tyrosine kinase: the preparation and structure-activity relationship of 4-anilino-3-cyanoquinolines and 4-anilinoquinazolines.

Src is a nonreceptor tyrosine kinase involved in signaling pathways that control proliferation, migration, and angiogenesis. Increased Src expression and activity are associated with an increase in tumor malignancy and poor prognosis. Several quinolines and quinazolines were identified as potent and selective inhibitors of Src kinase activity.

Enzyme Inhibitors↗

PubMed2000

[Modification of L-asparaginase with colominic acid and the new characteristics of the modified enzyme].

The colominic acid was covalently coupled to L-asparaginase molecule by reductive amination. Depending on the molar ratios of colominic acid-asparaginase (30:1, 50:1 and 100:1), a modified enzyme molecule contained 4.7, 7.2 and 12 colominic acid molecule, they retained 58%, 56% and 33.2% of the initial asparaginase activity, respectively. In comparison with the native enzyme, modified enzyme had lower immunogenicity and antigenicity, longer half-life time (in vitro), more resistance ability to trypsin proteolysis, and similar Km value for L-asparagine.

Asparaginase↗

PubMed1999

An agonist anti-human CD40 monoclonal antibody that induces dendritic cell formation and maturation and inhibits proliferation of a myeloma cell line.

CD40, a 48-50 KD cell membrane molecule, member of the nerve growth factor receptor and tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Anti-CD40 monoclonal antibody (MAb) has been shown earlier to costimulate with IgM or phorbol esters resting B cells to proliferate, differentiate, secrete immunoglobulins, and switch isotype. Here we report on an agonistic mouse anti-human CD40 MAb 5C11. The specificity of this MAb was verified by flow cytometry, Western blotting, and competition with anti-CD40 MAb 89. We studied the effects of MAb 5C11 on a multimyeloma cell line, XG2, that expresses the CD40 antigen strongly and found that this MAb caused the homotypic aggregation of XG2, strongly suppressed XG2 proliferation, and led to its apoptosis after 24 hr of treatment. Interestingly, MAb 5C11 also triggered the generation, proliferation, and maturation of dendritic cells from peripheral blood monocytes, either by itself or in combination with GM-CSF and IL-4.

Animals↗

PubMed1999

Three-dimensional arrangement of collagen fibrils in human ciliary body.

The purpose of this study is to visualize the three-dimensional arrangement of collagen fibrils in aged human ciliary body and discuss their significance. The ciliary bodies obtained from two human eyes were treated with a NaOH cell-maceration method for 7 days, then prepared conventionally for light and scanning electron microscopy. The general morphology of the collagen tissue in the ciliary body appeared almost the same as that normally observed. Cellular elements were completely removed, but collagen fibrils were well preserved. In the stroma of the ciliary body, collagen fibrils were arranged irregularly. In the areas of the radial and circular ciliary muscles, considerable numbers of collagen fiber bundles were observed running in a circular direction. A honeycomb structure was seen in the pars plana, the walls and base of which were formed by interweaving collagen fibrils. The results suggested that collagen fibrils in the aged human ciliary body may be largely involved in the presbyopia.

Aged↗

PubMed1998

Threshold distributions of phenylthiocarbamide (PTC) in the Chinese population.

The ability to taste phenylthiocarbamide (PTC) is a well-documented Mendelian trait. Mapping and cloning the gene(s) responsible for the PTC tasting ability would help to delineate the molecular basis for the variations in PTC tasting ability in humans and to shed new light on taste chemosensory functions. In view of the spectacular successes in genome science, the positional cloning strategy seems to be a feasible approach to the isolation of the gene(s) underlying the PTC tasting ability. As a first step toward mapping the gene(s), we collected PTC taste threshold data on 106 individuals, most of them being university students, in Shanghai, China. Using various parametric and nonparametric statistical methods, we have found that the data set is best described by a bimodal distribution. The frequency of PTC nontasters is estimated to be 10%. This is consistent with the view that the PTC nontasting ability follows a recessive mode of inheritance. Several authors had previously reported PTC data on Chinese living outside China. Our data are, to our knowledge, the first ever collected from the Chinese population within China.

Adolescent↗

PubMed1998

Rhs elements comprise three subfamilies which diverged prior to acquisition by Escherichia coli.

The Rhs elements are complex genetic composites widely spread among Escherichia coli isolates. One of their components, a 3.7-kb, GC-rich core, maintains a single open reading frame that extends the full length of the core and then 400 to 600 bp beyond into an AT-rich region. Whereas Rhs cores are homologous, core extensions from different elements are dissimilar. Two new Rhs elements from strains of the ECOR reference collection have been characterized. RhsG (from strain ECOR-11) maps to min 5.3, and RhsH (from strain ECOR-45) maps to min 32.8, where it lies in tandem with RhsE. Comparison of strain K-12 to ECOR-11 indicates that RhsG was once present in but has been largely deleted from an ancestor of K-12. Phylogenetic analysis shows that the cores from eight known elements fall into three subfamilies, RhsA-B-C-F, RhsD-E, and RhsG-H. Cores from different subfamilies diverge 22 to 29%. Analysis of substitutions that distinguish between subfamilies shows that the origin of the ancestral core as well as the process of subfamily separation occurred in a GC-rich background. Furthermore, each subfamily independently passed from the GC-rich background to a less GC-rich background such as E. coli. A new example of core-extension shuffling provides the first example of exchange between cores of different subfamilies. A novel component of RhsE and RhsG, vgr, encodes a large protein distinguished by 18 to 19 repetitions of a Val-Gly dipeptide occurring with a eight-residue periodicity.

Amino Acid Sequence↗

PubMed1997

Mapping of a cytoplasmic domain of the human growth hormone receptor that regulates rates of inactivation of Jak2 and Stat proteins.

It has been previously demonstrated that growth hormone (GH)-stimulated tyrosine phosphorylation of Jak2 and Stat5a and Stat5b occurs in FDP-C1 cells expressing either the entire GH receptor or truncations of the cytoplasmic domain expressing only the membrane-proximal 80 amino acids. However, other receptor domains that might modulate rates of GH activation and inactivation of this cascade have not been examined. Here we have defined a region in the human GH receptor between amino acids 520 and 540 in the cytoplasmic domain that is required for attenuation of GH-activated Jak/Stat signaling. Immunoprecipitations with antibodies to Jak2 indicate that the protein tyrosine phosphatase SHP-1 is associated with this kinase in cells exposed to GH. To address the possibility that SHP-1 could function as a negative regulator of GH signaling, liver extracts from motheaten mice deficient in SHP-1 or unaffected littermates were analyzed for activation of Stats and Jak2. Extracts from motheaten mice displayed prolonged activation of the Stat proteins as measured by their ability to interact with DNA and prolonged tyrosine phosphorylation of Jak2. These results delineate a novel domain in the GH receptor that regulates the inactivation of the Jak/Stat pathway and appears to be modulated by SHP-1.

Animals↗

PubMed1997

Escherichia coli strains with nonimmune immunoglobulin-binding activity.

We have identified several strains of Escherichia coli which contain immunoglobulin-binding activity on the cell surface. Affinity-purified antibodies ordinarily used as secondary antibodies in immunodetection protocols were bound by 6 of 72 strains of the ECOR reference collection of E. coli. The Fc fragments of both human and sheep immunoglobulin G (IgG) were also bound, demonstrating the nonimmune nature of the phenomenon. Binding of conjugated IgG Fc directly to unfixed cells was observed by fluorescence microscopy. Western blots showed that the immunoglobulin-binding material occurs in the form of multiple bands, with the apparent molecular masses of the most prominent bands exceeding 100 kDa. No two of the strains have the same pattern of bands. The binding activity in extracts was sensitive to proteinase K. The binding activity of intact cells was reduced preferentially by trypsin digestion, demonstrating exposure at the cell surface. Expression of binding activity in Luria-Bertani broth cultures was favored by a temperature of 37 degrees C and entry into stationary phase of growth.

Animals↗

PubMed1995

Mapping of the cytoplasmic domain of the human growth hormone receptor required for the activation of Jak2 and Stat proteins.

Incubation of cells with growth hormone (GH) stimulates both tyrosine phosphorylation of the Jak2 tyrosine kinase and, in some cells, the transcription factor Stat1 alpha (1-4). When the promyeloid cell line FDC-P1 is transfected with the human growth hormone receptor, these cells can grow in the presence of GH and in the absence of interleukin-3. Growth hormone treatment of cells expressing the human growth hormone receptor did not activate Stat1 alpha. However, a complex is present in extracts prepared from growth hormone-treated cells that binds to the gamma response region, an enhancer present in the promoter of the high affinity Fc gamma R1 receptor to which cytokine-activated Stat complexes bind. When truncations of the cytoplasmic domain of the receptor are expressed in FDC-P1 cells only the membrane-proximal 80 amino acids (containing box 1 and box 2) are required for activation of both a GH-stimulated binding activity (GHSF) and tyrosine phosphorylation of Jak2. Activation of GHSF can be inhibited in a cell-free system by the addition of a glutathione S-transferase fusion protein containing these 80 amino acids. Replacement of the one tyrosine in this region of the receptor with a phenylalanine does not alter the activation of either GHSF or Jak2, suggesting that tyrosine phosphorylation of the receptor is not required for GH activation of GHSF. Moreover, a cell line expressing a receptor with only the 54 membrane-proximal amino acids of the intracellular domain (including box 1) shows constitutively tyrosine-phosphorylated Jak2 as well as GHSF binding. With this truncated receptor, there is little if any additional GH-induced tyrosine phosphorylation of Jak2 or induced binding to the gamma response region. These results define the importance of the membrane-proximal 80 amino acids of the GH receptor (with the conserved box 1 and box 2 domains) with regard to GH activation of both Jak2 and Stat(s). They also suggest that within these domains there may be positive and negative elements that regulate Jak2 function.

Base Sequence↗

PubMed1995

Intracellular tyrosine residues of the human growth hormone receptor are not required for the signaling of proliferation or Jak-STAT activation.

Ligand binding and dimerization of the growth hormone (GH) receptor leads to the rapid tyrosine phosphorylation of the intracellular kinase, Jak2, to the tyrosine phosphorylation and activation of STAT protein(s) and to the tyrosine phosphorylation of the receptor itself. Expression of the human GH receptor in the mouse promyeloid, interleukin-3-dependent cell line, FDC-P1, shows that this receptor can signal ligand-dependent proliferation in these cells as well as induce the tyrosine phosphorylation of Jak2 and the activation of transcription factors. We now examine the requirement for tyrosine phosphorylation of the GH receptor for these three events by expression of a receptor without tyrosine residues in the intracellular domain. Six of the seven intracellular tyrosine residues were removed by a carboxyl-terminal truncation, and the remaining tyrosine was changed to phenylalanine to yield the GH receptor D351Stop/Y314F. When expressed in FDC-P1 cells, this receptor retained its ability to induce the tyrosine phosphorylation of Jak2, to induce the activation of transcription factors, and to signal ligand-dependent cell proliferation. Thus, tyrosine phosphorylation of the GH receptor is not essential for the signaling of these three events at least in this system. This finding contrasts with that for the interferon-gamma receptor system where data indicate that the specific tyrosine phosphorylation of the interferon-gamma receptor leads to an association with the STAT protein, p91, that is the mechanism by which ligand couples the receptor to the signal transduction system.

Amino Acid Sequence↗