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Biomedical subjects

Vincent Chan

Publications and source records attributed to Vincent Chan.

At least 37 records · Page 2Linked to original sources

Impact of secondary pulmonary hypertension on lung transplant outcome.

INTRODUCTION: Secondary pulmonary hypertension (SPH), defined as a mean pulmonary artery pressure (PAM) greater than 25 mm Hg, complicates end-stage lung diseases of varying etiology. Although previous studies have suggested that SPH does not adversely affect outcome, no study has assessed the impact of the degree of SPH. METHODS: A retrospective review of the lung transplant database was used to identify patients who underwent either single-lung (SLT) or bilateral lung transplantation (BLT) complicated by SPH. SPH patients were stratified into low SPH (PAM = 30-40 mm Hg) and high SPH (PAM > or = 40 mm Hg). Each group was further sub-categorized into SLT or BLT. Patients with a heart-lung transplant or primary pulmonary hypertension were excluded. Recipients without pulmonary hypertension transplanted over the same time were used as controls. Data are reported as controls vs low SPH vs high SPH. RESULTS: One hundred-four patients received lung transplants between August 1998 and March 2003. There were 45 patients (18 men and 27 women) with SPH. Of these, 28 patients had low SPH, and 17 patients had high SPH. Forty-two patients (18 men and 24 women) without PH were the controls. There were no significant differences between groups except pre-operative oxygen dependence (81% vs 100% vs 94%, respectively) and use of CPB (28.6% vs 57.1% vs 64.7%, respectively). PAO2-PaO2 gradients and PaO2/FIO2 ratios were significantly worse in the high SPH group (116.2 vs 132.9 vs 186.3; p < 0.006) and (277.8 vs 234.3 vs 214.4; p < 0.026) respectively. There was no statistical difference in length of mechanical ventilation or duration of intensive care unit stay between groups. PAMs were significantly different pre-operatively (22.2 +/- 0.8 vs 34.0 +/- 0.6 vs 47.8 +/- 2.0; p < 0.001) and post-operatively (20.9 +/- 1.1 vs 23.7 +/- 1.3 vs 24.8 +/- 2.1; p < 0.001). There were no operative deaths. There were 3 early deaths in the control group, 1 in the low SPH group, and 3 in the high SPH group, none were related to pulmonary hypertension. Actuarial survival at 12, 24, and 48 months was not significantly different among the groups nor between SLT or BLT with SPH. CONCLUSION: Although SPH increases the risk of reperfusion injury; survival is equivalent with mild or moderate pulmonary hypertension. Either SLT or BLT may be used in patients with SPH without compromising outcome. This has the added benefit of expanding the donor pool.

Adult↗

Dynamic kinetic resolution of atropisomeric amides.

[reaction: see text] Using L-proline as catalyst in the asymmetric aldol reaction and a series of benzamides and naphthamides, we have accomplished a dynamic kinetic resolution that simultaneously establishes the stereochemistry of the atropisomeric amide's chiral axis and a stereogenic center. The enantioselectivities ranged from 82% to 95% and the diastereoselectivities from 2.1:1 to 7.0:1.

Amides↗

A quantitative contour analysis of axisymmetric vesicles spontaneously adhering onto a substrate.

The determination of membrane-substrate profile for adherent vesicle using confocal reflectance interference contrast microscopy (C-RICM) has pushed for the need of advanced mechanics model for interpreting adhesion mechanisms. In this work, a model for vesicles or cells adhesion is established, the governing equation is derived from the variation of the potential energy at the cohesive zone. A closed-form solution is found for vesicle spontaneously adheres to a substrate when its shear modulus, micro vanishes. Based on the model and C-RICM experiments the magnitude of the adhesion force is calculated for a lipid vesicle adheres to a glass substrate.

Biocompatible Materials↗

Bioadhesive characterization of poly(methylidene malonate 2.12) microparticle on model extracellular matrix.

The efficacy of a drug delivery system is predicated on its retention in the target tissue. Microparticle is one of the most popular and effective drug delivery configurations. Recently, it has been shown that the interaction between drug-loaded microparticles and tissues is related to the effectiveness of paclitaxel delivery to the bladder wall of mice for treating superficial bladder cancer. In this study, the adhesive interaction between poly(methylidene malonate 2.12) or PMM 2.1.2 microparticles and collagen, which serves as the model extracellular matrix for bladder wall, was probed with confocal reflectance interference contrast microscopy (C-RICM), single-particle compressive force measurement and contact mechanics theory. Young's modulus of single PMM 2.1.2 microparticle was determined as 1.56 +/- 0.25 x 10(4)N/m(2). For plain PMM 2.1.2 microparticle in water (pH 5.5), the degree of deformation (a/R) on collagen coated substrate decreased from 0.77 to 0.26 against the increase of mid-plane diameter from 2 to 18 microm. The adhesion energy of PMM 2.1.2 microparticle was determined from Maguis-JKR theory and remained at around 1.5 mJ/m(2) against the increase of particle diameter. At pH 4, the average degree of particle deformation and adhesion energy was increased by 11% and 32%, respectively, in comparison with that at pH 5.5. The loading of paclitaxel in PMM 2.1.2 microspheres enhanced the deformation and adhesion of microspheres at pH 5.5. It is hypothesized that the electrostatic repulsion between paclitaxel and collagen at pH 4 reduces the adhesion energy of PMM 2.1.2-paclitaxel microsphere. This study may offer insight for design of future microparticulate delivery systems by providing the experimental and theoretical tools to study the bioadhesive interaction between drug-loaded microparticles and model extracellular matrices.

Adhesiveness↗

Shape recovery of an optically trapped vesicle: effect of flow velocity and temperature.

A new biophysical approach based on optical tweezers is developed to measure the time-dependent shape transformation and recovery of a single liposome, which is induced by the sudden stop of a moving liposome from various flow velocities at constant temperature. A simple viscoelastic model has been applied to correlate the temporal geometric parameter of the deformed liposome with a characteristic time constant, i.e., the ratio of membrane viscosity to elasticity. Our results show that membrane viscosity becomes dominant in governing the shape recovery rate when sample temperature goes beyond the main phase transition temperature of the phospholipid bilayer. More importantly, flow speed and vesicle size are demonstrated as key physical determinants for the shape recovery of liposome.

1,2-Dipalmitoylphosphatidylcholine↗

Degenerate peptide recognition by Candida albicans adhesins Als5p and Als1p.

Candida albicans and Saccharomyces cerevisiae expressing the adhesins Als5p or Als1p adhere to immobilized peptides and proteins that possess appropriate sequences of amino acids in addition to a sterically accessible peptide backbone. In an attempt to further define the nature of these targets, we surveyed the ability of yeast cells to adhere to 90- micro m-diameter polyethylene glycol beads coated with a 7-mer peptide from a library of 19(7) unique peptide-beads. C. albicans bound to ca. 10% of beads from the library, whereas S. cerevisiae expressing Als5p or Als1p bound to ca. 0.1 to 1% of randomly selected peptide-beads. S. cerevisiae expressing Als1p had a distinctly different adherence phenotype than did cells expressing Als5p. The former adhered in groups or clumps of cells, whereas the latter adhered initially as single cells, an event which was followed by the build up of cell-cell aggregates. Beads with adherent cells were removed, and the peptide attached to the bead was determined by amino acid sequencing. All adhesive beads carried a three-amino-acid sequence motif (tau phi+) that possessed a vast combinatorial potential. Adherence was sequence specific and was inhibited when soluble peptide identical to the immobilized peptide was added. The Als5p adhesin recognized some peptides that went unrecognized by Als1p. The sequence motif of adhesive peptides identified by this method is common in proteins and offers so many possible sequence combinations that target recognition by the Als proteins is clearly degenerate. A degenerate recognition system provides the fungi with the potential of adhering to a multitude of proteins and peptides, an advantage for any microorganism attempting to establish a commensal or pathogenic relationship with a host.

Amino Acid Sequence↗

Effect of acyl chain mismatch on the contact mechanics of two-component phospholipid vesicle during main phase transition.

It has been recently demonstrated that acyl chain mismatch of phospholipid bilayer composed of a binary lipid mixture induces component formation on the lateral plane of the bilayer [Biophys. J. 83 (2002) 1820-1883]. In this report, the contact mechanics of unilamellar vesicles composed of binary dimyristoyl-phosphatidylcholine (DMPC)/dipalmitoyl-phosphocholine (DPPC) mixtures on fused silica and amino-modified substrates is simultaneously probed by confocal-reflectance interference contrast microscopy (C-RICM) and cross-polarized light microscopy during gel to liquid crystalline transition of the lipid bilayer. C-RICM results indicate that the average degree of vesicle deformation for DMPC-rich and DPPC-rich vesicles adhering on fused silica substrate is increased by 30% and 14%, respectively, in comparison with that in pure DMPC and DPPC vesicles. Also, lateral heterogeneity induced by acyl chain mismatch increases the average magnitude of adhesion energy in DMPC-rich and DPPC-rich vesicles of all sizes by 6.4 times and 2.3 times, respectively. Similar modulation of adhesion mechanics induced by carbon chain difference is obtained on amino-modified substrate. Most importantly, the thermotropic transition of the mixed bilayer from gel (below T(m)) to fluid phase (above T(m)) further exemplifies the effect of acyl chain mismatch on the increases of degree of vesicle deformation and adhesion energy.

1,2-Dipalmitoylphosphatidylcholine↗

Adhesion contact dynamics of HepG2 cells on galactose-immobilized substrates.

The specific recognition between asialoglycoprotein receptor and galactose ligand at cell-substrate interfaces has been shown to mediate hepatocyte adhesion and maintain liver specific functions of hepatocytes. Conventionally, the success of hepatocyte attachment on engineered tissue scaffold is inferred from the degree of two-dimensional cell spreading that is measured by transmitted light microscopy. However, the actual contact mechanics and adhesion strength of hepatocytes during two-dimensional cell spreading has not been elucidated due to lack of biophysical probe. In this study, a novel biophysical technique known as confocal reflectance interference contrast microscopy (C-RICM) in conjunction with phase contrast microscopy is utilized to probe the adhesion dynamics, contact mechanics and two-dimensional spreading kinetics of HepG2 cells on galactose immobilized and collagen gel coated substrates. C-RICM demonstrates that HepG2 cells form strong adhesion contacts with both galactose-immobilized surfaces and collagen gel coated substrates. Moreover, HepG2 cells maintain their compact shapes in the presence of asialoglycoprotein receptor-mediated recognition while they become exceedingly spread under integrin-mediated adhesion on collagen gel coated substrate. The initial rate of adhesion contact formation and the steady-state adhesion energy of HepG2 cell population are highest on substrate conjugated with galactose ligand via a longer spacer. The adhesion dynamics and final adhesion energy of HepG2 cells depends both on the type of ligand-receptor interaction and the length of spacer between the ligand and substrate. Most importantly, new biophysical insights into the initial hepatocyte attachment that are critical for hepatocyte culture are provided through the decomposition of two-dimensional spreading and adhesion contact formation on bio-functional substrates.

Animals↗

Thermal effect on a viscously deformed liposome in a laser trap.

The viscous drag and mechanical deformation of a single vesicle under hydrodynamics flow during the phase transition of a lipid bilayer is determined by optical tweezers experiments with the aid of computational fluid dynamics simulations. Based on the experimental geometry of the vesicle under hydrodynamics flow, the surface stresses and drag force are numerically calculated. It is found that the vesicle is less rigid and the viscous drag force of the vesicle decreases with the increase of temperature at low Reynolds number flow during sample heating. Interestingly, these mechanical properties are reversible and depend strongly on the liposome's thermotropic phase transition temperature. Overall, this study provides new insights into highly coupled thermal and hydrodynamics effects on the biomechanical properties of model membrane vesicle in physiological flow systems.

1,2-Dipalmitoylphosphatidylcholine↗

Contact deformation of liposome in the presence of osmosis.

The role of osmotic pressure on the geometry of adherent liposome remains an intricate question in the mechanics of supramolecular structures. In this study, confocal reflection interference contrast microscopy in combination with cross-polarized microscopy was applied to probe the geometry of deformed liposome on fused silica substrates through the determination of a vesicle-substrate separation profile. In parallel, a theoretical model which describes the large deformation of the lipid bilayer membrane under both out-plane bending and in-plane shear forces is developed. Then, the global deformation geometry of the adherent liposome is rigorously compared with our experimental data. It is shown that the adhesion contact area increases in dimension, the liposome volume decreases, and the vesicle height decreases under the reduced osmotic pressure. The coupling of experimental data and a modified theoretical framework of the adherent liposome provides a more explicit result in comparison with previous studies and demonstrates the possibility of modeling the change of liposome mechanics under the influence of osmosis.

Adsorption↗

Substrate-induced deformation and adhesion of phospholipid vesicles at the main phase transition.

The physiochemical properties of phospholipid vesicle, e.g. permeability, elasticity, etc., are directly modulated by the chain-melting transition of the lipid bilayer. Currently, there is a lack of understanding in the relationship between thermotropic transition, mechanical deformation and adhesion strength for an adherent vesicle at temperature close to main phase transition temperature T(m). In this study, the contact mechanics of dimyristoyl-phosphatidylcholine (DMPC) vesicle at the main phase transition are probed by confocal reflectance interference contrast microscopy in combination with phase contrast microscopy. It is shown that DMPC vesicles strongly adhere on pure fused silica substrate at T(m) and the degree of deformation as well as the adhesion energy is a decreasing function against the mid-plane diameter of the vesicles. Furthermore, an increase of osmotic pressure at the gel/liquid crystalline phase co-existence imposes insignificant changes in both the degree of deformation and adhesion energy of adherent vesicles when the lipid bilayer permeability is maximized. With the reverse of substrate charge, the mechanical deformation and adhesion strength for larger vesicles (mid-plane diameter >18 microm) are significantly reduced. By monitoring the parametric response of substrate-induced vesicle adhesion during main phase transition, it is shown that the degree of deformation and adhesion energy of adhering vesicle is increased and unchanged, respectively, against the increase of temperature.

Adhesiveness↗

Transient analysis of electroosmotic flow in a slit microchannel.

The transient aspects of electroosmotic flow in a slit microchannel are studied. Exact solutions for the electrical potential profile and the transient electroosmotic flow field are obtained by solving the complete Poisson-Boltzmann equation and the Navier-Stokes equation under an analytical approximation for the hyperbolic sine function. The characteristics of the transient electroosmotic flow are discussed under influences of the electric double layer and the geometric size of the microchannel.

Journal Article↗

Thermal induced modification of the contact mechanics of adhering liposomes on cationic substrate.

The correlation between the mechanical property and the thermotropic transition of the phospholipid bilayer has been recently demonstrated (Chem. Phys. Lipids 110 (2001) 27). However, the role of thermal induced mechanical responses of phospholipid bilayer on the contact mechanics of liposome adhering on a cationic substrate has not been determined. In this study, confocal-reflectance interference contrast microscopy, phase contrast microscopy and contact mechanics modeling are applied to probe the adhesion mechanisms of liposomes in the presence of electrostatic interactions during the thermotropic transition of the lipid bilayer. When temperature increases from 23 to 49 degrees C at pH 7.4, the degree of liposome deformation (a/R) and adhesion energy of dipalmitoyl-sn-glycero-3-phosphocholine liposome increases by 10% and remains constant, respectively, on 3-amino-propyl-triethoxy-silane (APTES) modified substrate. The extents of increase in these two parameters are highly dependent on the physicochemical properties of the rigid substrate. At pH 4, the adhesion energies above and below the phase transition temperature (T(m)) are increased by one order of magnitude due to the formation of the free silanol groups on APTES substrate. In hypotonic condition, the degree of vesicle deformation remains constant and the adhesion energy reduces by 20% during sample heating. Under all conditions, the adhesion energy of the adhering liposome spans a few orders of magnitude against the increase of liposome size as the surface area to volume ratio is maximized in smallest vesicle.

1,2-Dipalmitoylphosphatidylcholine↗

Echocardiographic assessment of cardiac structure and function in rats.

BACKGROUND: Echocardiography is used in humans to characterise the structure and function of the heart, yet is relatively uncommon in studies on the rat, the most commonly used model of human cardiovascular disease. The aim of this study was to show that echocardiography in rats provides useful information on cardiac changes occurring in thyroid dysfunction and can also be used to characterise cardiac abnormalities. METHODS: Transthoracic echocardiography and Doppler techniques with high frequency, high frame rate imaging were used to define cardiac dimensions and function in 240 Wistar rats and cardiac abnormalities in Wistar and spontaneously hypertensive rats (SHR). RESULTS: Echocardiographic assessment of left ventricular dimensions and function and aortic flows was technically feasible in almost all adult Wistar rats and SHR, including those with thyroid dysfunction and cardiac abnormalities. Pulsed-wave Doppler profiles of mitral inflows to estimate diastolic function were less reliably obtained. CONCLUSIONS: Echocardiography is a powerful technique for non-invasive and serial determination of cardiac structure and function in rat models of human cardiovascular disease.

Journal Article↗

Modifiers of patient-controlled analgesia efficacy. I. Locus of control.

The effectiveness of patient-controlled analgesia (PCA) depends upon the patient's appropriate response to a strong aversive stimulus (i.e., pain) with subsequent reinforcement (i.e., opiate injection). Each patient may have psychological characteristics that modify this response to aversive stimuli. To test for such characteristics, 76 female patients undergoing abdominal gynecologic procedures were given psychological tests (i.e., the Chance External, Powerful Others External, and Internal subscales of the Multidimensional Health Locus of Control; the Activities of Daily Living scale; and the Hypochondriasis, Depression, and Hysteria scales of the Minnesota Multiphasic Personality Inventory). Patients utilized PCA for postoperative analgesia. At the completion of PCA, patients were given a questionnaire assessing both the level of pain and degree of satisfaction with pain relief. Correlational analysis compared the level of pain and degree of satisfaction with results of psychological testing. Results showed that female patients with an external locus of control had higher levels of pain and greater dissatisfaction with PCA. An internal locus of control was predictive of lower pain scores and increased satisfaction. PCA effectiveness, as measured by the level of pain and degree of patient satisfaction, correlated with results of psychological testing. The delineation of these and other possible modifiers of PCA efficacy may define populations that are optimally responsive to PCA.

Analgesics↗