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D A Wang

Publications and source records attributed to D A Wang.

14 recordsLinked to original sources
PubMed2006

Simulating tele-manipulator controlled tool-tissue interactions using a nonlinear FEM deformable model.

Enhanced visualization of an operating scene presented by a robotically assisted tele-manipulator system such as the da Vinci(TM) can be provided through the use of augmented reality facilities. Generating overlays from 3D models and the intra-operative video allows the surgeon to acquire greater information about the surgical scene. Tool-tissue interactions must be tracked to ensure the overlays are updated regularly and accurately. The work presented here describes how these interactions may be modelled by integrating a nonlinear finite element model with the 3D reconstruction and using the tool kinematic data as input to the deformation.

Connective Tissue↗
PubMed2001

A single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipid growth factor receptors.

The phospholipid growth factors sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are ligands for the related G protein-coupled receptors S1P(1)/EDG1 and LPA(1)/EDG2, respectively. We have developed a model of LPA(1) that predicts interactions between three polar residues and LPA. One of these, glutamine 125, which is conserved in the LPA receptor subfamily (LPA(1)/EDG2, LPA(2)/EDG4, and LPA(3)/EDG7), hydrogen bonds with the LPA hydroxyl group. Our previous S1P(1) study identified that the corresponding glutamate residue, conserved in all S1P receptors, ion pairs with the S1P ammonium. These two results predict that this residue might influence ligand recognition and specificity. Characterization of glutamate/glutamine interchange point mutants of S1P(1) and LPA(1) validated this prediction as the presence of glutamate was required for S1P recognition, whereas LPA recognition was possible with either glutamine or glutamate. The most likely explanation for this dual specificity behavior is a shift in the equilibrium between the acid and conjugate base forms of glutamic acid due to other amino acids surrounding that position in LPA(1), producing a mixture of receptors including those having an anionic glutamate that recognize S1P and others with a neutral glutamic acid that recognize LPA. Thus, computational modeling of these receptors provided valid information necessary for understanding the molecular pharmacology of these receptors.

Amino Acid Sequence↗
PubMed2001

Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: a possible role in regulating cardiac function via sphingolipid receptors.

Blood plasma and serum contain factors that activate inwardly rectifying GIRK1/GIRK4 K+ channels in atrial myocytes via one or more non-atropine-sensitive receptors coupled to pertussis-toxin-sensitive G-proteins. This channel is also the target of muscarinic M(2) receptors activated by the physiological release of acetylcholine from parasympathetic nerve endings. By using a combination of HPLC and TLC techniques with matrix-assisted laser desorption ionization-time-of-flight MS, we purified and identified sphingosine 1-phosphate (SPP) and sphingosylphosphocholine (SPC) as the plasma and serum factors responsible for activating the inwardly rectifying K+ channel (I(K)). With the use of MS the concentration of SPC was estimated at 50 nM in plasma and 130 nM in serum; those concentrations exceeded the 1.5 nM EC(50) measured in guinea-pig atrial myocytes. With the use of reverse-transcriptase-mediated PCR and/or Western blot analysis, we detected Edg1, Edg3, Edg5 and Edg8 as well as OGR1 sphingolipid receptor transcripts and/or proteins. In perfused guinea-pig hearts, SPC exerted a negative chronotropic effect with a threshold concentration of 1 microM. SPC was completely removed after perfusion through the coronary circulation at a concentration of 10 microM. On the basis of their constitutive presence in plasma, the expression of specific receptors, and a mechanism of ligand inactivation, we propose that SPP and SPC might have a physiologically relevant role in the regulation of the heart.

Animals↗
PubMed2001

Blends of stearyl poly(ethylene oxide) coupling-polymer in chitosan as coating materials for polyurethane intravascular catheters.

To optimize the surface biocompatibility of the intravascular catheter, an amphiphilic coupling-polymer of stearyl poly (ethylene oxide) -co- 4,4'-methylene diphenyl diisocyanate-co- stearyl poly (ethylene oxide), for short MSPEO, was specially designed as the surface modifying additive (SMA). The blend of MSPEO in chitosan was coated on the outer wall of the catheters by the dip-coating method. The surface analysis was carried out by ATR-FTIR and contact angle measurements. The surface enrichment of MSPEO was confirmed. On the water interface, the larger the molecular weight of PEO was, the higher the surface enrichment. While on air interface, the case was the contrary. Three kinds of static test of clotting time, plasma recalcification time (PRT), prothrombin time (PT), and thrombin time (TT), as well as the static platelet adhesion experiment were carried out. The results indicated that the coated surface could resist the clotting effectively. In order to test the blood-compatibility of the coated catheters under a shear of blood flow, the dynamic experiment was performed through a closed-loop tubular system with the shear rate of 1500 s(-1). The results of blood regular testing at six different times (0, 5,10, 20, 30, and 60 min) indicated that the biocompatibility of the coating was nearly ideal. Finally, the SMA-MSPEO was proved to be non-chronic-toxic by animal experiments with rats and suitable as a coating material for clinical use.

Animals↗
PubMed2001

Surface coating of stearyl poly(ethylene oxide) coupling-polymer on polyurethane guiding catheters with poly(ether urethane) film-building additive for biomedical applications.

Three types of stearyl poly(ethylene oxide) (SPEO) with Mn of 2,300, 6,000 and 12,000 were synthesized; accordingly, three types of amphiphilic coupling-polymer SPEO-MDI-SPEO (MSPEO) were prepared by the reactions with 4,4'-methylene diphenyl diisocyanate (MDI). As the surface-modifying additives (SMA), MSPEOs were coated onto the outer wall of the medical guiding catheters. Due to the lack of stability, when coated, MSPEO blended with the film building agent (FBA), poly(ether urethane) (PEL). The process of coating was performed with a lifter. With invariable speed, the PU guiding catheter was vertically dipped into the coating mixture of SMA-MSPEO and FBA-PEL. The surface analysis was carried out by ATR-FTIR and contact angle measurements. It was proved that the surface enrichment of PEO on water interface was much higher than that on air interface. Three kinds of static clotting time tests, PRT, PT and TT, as well as the static platelet adhesion experiment were performed. The results indicated that the coated surface could resist the blood coagulation effectively. In order to test the blood compatibility of the coated catheters under a shear of blood flow, the dynamic experiment was performed with a closed-loop tubular system under a shear rate of 1,500 s(-1). The blood regular testing was carried out on the samples taken out at six different times (0, 5,10, 20, 30 and 60 min). The results were ideal. Finally, the SMA-MSPEO was proved to be non-acute-toxic by LD50 test.

Blood Coagulation↗
PubMed2001

Selective binding of albumin on stearyl poly(ethylene oxide) coupling polymer-modified poly(ether urethane) surfaces.

A tri-block-coupling polymer of stearyl poly(ethylene oxide)-4,4'-methylene diphenyl diisocyanate-stearyl poly(ethylene oxide) (MSPEO), was used as a surface modifying additive (SMA) and the MSPEO-modified poly(ether urethane) (PEU) surfaces were prepared by the process of dip-coating. The surface analysis by XPS revealed the surface enrichment of poly(ethylene oxide) (PEO). On the coating-modified surfaces, the bovine serum albumin (BSA) adsorption, respectively, from the low and high BSA bulk concentration solutions was correspondingly characterized by the methods of radioactive 125I-probe and ATR-FTIR. The bovine serum fibrinogen (Fg)-adsorption from the Fg bulk solution and the BSA-Fg competing adsorption from the BSA-Fg binary solutions were also characterized by radioactive 125I-probe. The reversible BSA-selective in situ adsorption on MSPEO-modified PEU surfaces were achieved, and the performance of blood compatibility on the coating-modified surfaces was also confirmed, respectively, by plasma recalcification time (PRT) and prothrombin time (PT) tests.

Adsorption↗
PubMed2000

Lipid phosphate phosphatase-1 and Ca2+ control lysophosphatidate signaling through EDG-2 receptors.

The serum-derived phospholipid growth factor, lysophosphatidate (LPA), activates cells through the EDG family of G protein-coupled receptors. The present study investigated mechanisms by which dephosphorylation of exogenous LPA by lipid phosphate phosphatase-1 (LPP-1) controls cell signaling. Overexpressing LPP-1 decreased the net specific cell association of LPA with Rat2 fibroblasts by approximately 50% at 37 degrees C when less than 10% of LPA was dephosphorylated. This attenuated cell activation as indicated by diminished responses, including cAMP, Ca(2+), activation of phospholipase D and ERK, DNA synthesis, and cell division. Conversely, decreasing LPP-1 expression increased net LPA association, ERK stimulation, and DNA synthesis. Whereas changing LPP-1 expression did not alter the apparent K(d) and B(max) for LPA binding at 4 degrees C, increasing Ca(2+) from 0 to 50 micrometer increased the K(d) from 40 to 900 nm. Decreasing extracellular Ca(2+) from 1.8 mm to 10 micrometer increased LPA binding by 20-fold, shifting the threshold for ERK activation to the nanomolar range. Hence the Ca(2+) dependence of the apparent K(d) values explains the long-standing discrepancy of why micromolar LPA is often needed to activate cells at physiological Ca(2+) levels. In addition, the work demonstrates that LPP-1 can regulate specific LPA association with cells without significantly depleting bulk LPA concentrations in the extracellular medium. This identifies a novel mechanism for controlling EDG-2 receptor activation.

Animals↗
PubMed2000

Pharmacological characterization of phospholipid growth-factor receptors.

The phospholipid growth-factor (PLGE) terminology is proposed to describe a group of endogenous glycerol- and sphingolipid mediators that regulate cell proliferation through plasma membrane receptors. In addition to LPA and SPP, multiple PLGFs are present in blood plasma and serum. PLGF activity is regulated by its stimulus-coupled production and by endogenous inhibitors. In addition to LPA and SPP, alkenyl-glycerophosphate, cyclic-phosphatidic acid, and sphingosylphosphorylcholine were detected in biological fluids using mass spectrometry. Heterologous desensitization studies indicate the expression of multiple LPA-activated receptors in a variety of cell types, which are differentially activated by the different PLGFs. Northern blot and RT-PCR results reinforce the coexpression of PSP24 alpha and different members of the EDG1-7 receptors in the same cell. Stable heterologous expression of the PSP24 alpha, EDG2, and EDG4 receptors in HEK293 cells show distinct PLGF specificities and dose-response properties for each receptor subtype. Thus, both the controlled availability of the different agonists/inhibitors and the regulated expression of their receptors regulate the biological effects of PLGFs.

Animals↗
PubMed2000

Phospholipid growth factors and corneal wound healing.

In many tissue types, wound healing involves cell division and migration over and into the wound area to cover and remodel the wound. LPA and other members of the phospholipid lipid growth factor (PLGF) family stimulate many of the activities involved in wound healing. In the rabbit cornea, we have found that keratocytes from wounded corneas have a volume-activated Cl- current activated by LPA and alkenyl-LPA. This current is minimally activated by cyclic PA and SPC, and is not activated by LPA in cells from uninjured corneas. Biochemical examination of PLGFs in aqueous humor and lacrimal fluid before and after wounding identified LPA, alkenyl-GP, PA, and lyso PS, with elevated PLGF activity after wounding. In recent experiments examining human corneal cell lines and cultured cells using RT-PCR, we found mRNA for EDG receptors 1-5, with an apparent increase in EDG-3, -4, and -5 following brief SDS application to cell lines, and EDG receptors 2-5 induction in late-passage human corneal epithelial cells. This work points to a significant role for PLGFs in the corneal wound-healing process.

Animals↗
PubMed1999

Lysophosphatidic acid as a regulator of endothelial/leukocyte interaction.

Lysophosphatidic acid (LPA) is produced by a variety of activated cell types and acts as an intercellular mediator of processes associated with inflammation and repair including platelets aggregation, and smooth muscle and fibroblast proliferation. However no previous studies have examined the effects of LPA on endothelial cell leukocyte interactions. We have examined the ability of LPA to activate human aortic endothelial cells (HAEC) to bind monocytes, neutrophils, and HL60 cells (a neutrophil surrogate). Treatment of HAEC for 4 hours with 10 microM LPA caused an increase in the binding of monocytes, neutrophils, and HL60. LPA but not phosphatidic acid dose-dependently increased E-selectin and vascular cell adhesion molecule-1 (VCAM-1) cell surface expression. We performed several studies to characterize the receptor mediating the LPA effect. We demonstrate that at least five potential LPA receptors are expressed by HAEC: Edg-1, -3, -4, and -5 as well as PSP24. Cyclic phosphate-containing phosphatidic acid analogue, an agonist for the type 3 low affinity LPA receptor, was not effective in activating HAEC to bind leukocytes, excluding a role for this receptor. The selective receptor antagonists N-palmitoyl-serine and N-palmitoyl-tyrosine (which inhibits PSP24) completely inhibited LPA-induced VCAM expression; however these antagonists inhibited E-selectin expression by only 30%, suggesting a role for at least one additional LPA receptor mediating E-selectin expression. We propose that Edg-1 might be the second receptor, because this receptor, when expressed in HEK293 cells, similarly to the PSP24 receptor, caused ERK activation to nanomolar concentration of LPA. Exposure of HAEC to sphingosine-1-phosphate, another Edg-1 receptor agonist, increased surface expression of E-selectin and to a much smaller extent VCAM-1. The effects of both LPA and sphingosine-1-phosphate on the induction of both VCAM-1 and E-selectin expression was abolished by pretreatment with pertussis toxin suggesting that both LPA receptors in HAEC couple to a Gi pathway. These findings reveal an important and novel role for LPA and its receptors in inflammatory processes.

Animals↗
PubMed1998

Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment.

Hearing impairment is the most commonly occurring condition that affects the ability of humans to communicate. More than 50% of the cases of profound early-onset deafness are caused by genetic factors. Over 40 loci for non-syndromic deafness have been genetically mapped, and mutations in several genes have been shown to cause hearing loss. Mutations in the gene encoding connexin 26 (GJB2) cause both autosomal recessive and dominant forms of hearing impairment. To study the possible involvement of other members of the connexin family in hereditary hearing impairment, we cloned the gene (GJB3) encoding human gap junction protein beta-3 using homologous EST searching and nested PCR. GJB3 was mapped to human chromosome 1p33-p35. Mutation analysis revealed that a missense mutation and a nonsense mutation of GJB3 were associated with high-frequency hearing loss in two families. Moreover, expression of Gjb3 was identified in rat inner ear tissue by RT-PCR. These findings suggest that mutations in GJB3 may be responsible for bilateral high-frequency hearing impairment.

Adult↗
PubMed1998

Spinocerebellar ataxia type 2 in China: molecular analysis and genotype-phenotype correlation in nine families.

Sixteen patients from nine Chinese families with spinocerebellar ataxia type 2 (SCA2) were heterozygous for a CAG repeat expansion in the SCA2 gene containing 37 to 56 repeats, whereas the normal alleles carried 14 to 28 repeats. One or two CAA triplets within the CAG tract were seen in normal, but not in the expanded alleles. A strong inverse correlation was established between the number of CAG repeats and the age of disease onset. SCA2 accounted for 12% of the known Chinese families with spinocerebellar ataxia.

Adolescent↗
PubMed1998

[Studies on the mechanism of alpha-MSH in reducing IL-1 beta-induced fever].

The effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on IL-1 beta-induced fever and release of hypothalamic cAMP was observed in the present work. The results showed that alpha-MSH markedly suppressed febrile response (P < 0.05) and decreased the cAMP content in hypothalamus in response to icv injection of IL-1 beta (P < 0.01). The cAMP content of the medium in which the hypothalamic was incubated for 40 min in the presence of IL-1 beta was significantly increased (P < 0.01). However, this increase action could be prevented by a pretreatment with alpha-MSH. The results indicate that the inhibitory effect of alpha-MSH on the enhanced synthesis and release of cAMP in hypothalamus exposed to IL-1 beta might be one of the mechanisms of suppressing fever induced by IL-1 beta.

Analgesics, Non-Narcotic↗