Biomedical subjects

Eric Lee

Publications and source records attributed to Eric Lee.

31 records · Page 2Linked to original sources

PubMed2004

Electrophoresis of a concentrated dispersion of spherical particles in a non-Newtonian fluid.

Electrophoresis is one of the most widely used analytical tools for the quantification of the charged conditions on the surface of fine particles including biological entities. Although it has been studied extensively in the past, relevant results for the case when the dispersion medium is non-Newtonian are very limited. This may occur, for example, when the concentration of the dispersed phase is not low, which is not uncommon in practice. Here, the electrophoresis of a concentrated spherical dispersion in a Carreau fluid is analyzed theoretically under the conditions of low electric potential and weak external applied electrical field. A pseudospectral method coupled with a Newton-Raphson iteration procedure is used to solve the electrokinetic equations describing the phenomenon under consideration. We conclude that the more significant the shear thinning effect of the fluid, the larger the mobility, and this phenomenon is pronounced for the case when the double layer surrounding a particle is thin. We show that if the double layer is thin and the effect of shear thinning is significant, a second vortex can be observed in the neighborhood of a particle.

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PubMed2004

Obesity in BSB mice is correlated with expression of genes for iron homeostasis and leptin.

OBJECTIVE: We searched for genes whose alleles cause obesity and novel pathways correlated with obesity. RESEARCH METHODS AND PROCEDURES: BSB mice are a model of complex obesity due to interactions among genes from C57BL/6J (B) and Mus spretus (SPRET) in (B x SPRET) x B backcross mice. Stringent criteria identified 50 genes differentially expressed in epididymal adipose tissue from 7 pairs of lean vs. obese BSB mice. Quantitative reverse transcription-polymerase chain reaction of adipose tissue RNA from 48 BSB mice with a range of obesity was assayed. Leptin was evaluated in inbred (SPRET/Ei) and outbred (SPRET/Pt) BSB mice. RESULTS: Leptin (Lep) and adipsin expressions had the greatest fold differences between obese and lean mice. Four genes involved in iron homeostasis were included in the 50 differentially expressed genes [hemochromatosis (Hfe), diaphorase 1, transferrin receptor (Trfr) 2, and protoporphyrinogen oxidase] and two additional iron-related genes did not quite meet the stringent criteria for differential expression (Trfr and lactotransferrin). Hfe and Trfr mRNA levels and liver iron were negatively correlated with fat mass. Variation in obesity phenotypes explained 49%, 40%, and 37%, respectively, of the variance in Hfe, Lep, and Trfr mRNA levels. Leptin differed by haplotype at the Lep locus in outbred BSB. The quantitative trait locus identified in the outbred cross did not occur in inbred BSB. DISCUSSION: Our results suggest that iron homeostasis in BSB mice is coordinately regulated in vivo in adipose depots in response to obesity. Lep alleles derived from outbred, but not inbred, SPRET are a positional candidate for the chromosome 6 quantitative trait locus in BSB mice.

Alleles↗

PubMed2003

Prediction of Brownian particle deposition in porous media using the constricted tube model.

The deposition of colloidal particles onto the collector surfaces of porous media is investigated using the Brownian dynamics simulation method. The pore structure in a filter bed was characterized by the constricted tube model. The effects of various shapes of the total interaction energy curves of DLVO theory and the effects of different particle diameters on the collection efficiencies of particles are examined. The simulation results show that the particle collection efficiency is strongly dependent on the geometry of the tube and on the shape of the total interaction energy curve. In a comparison with the available experimental measurements of the filter coefficient, it is found that the present model can give a smaller discrepancy than that of the convective diffusion model in the unfavorable deposition region.

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PubMed2003

Dynamic electrophoretic mobility of a sphere in a spherical cavity.

Dynamic electrophoresis is a powerful analytical tool for the description of the surface properties of the charged entities in a concentrated dispersion. In our study the boundary effect on this dynamic phenomenon is investigated theoretically for the case, when the surface potential is low. In particular, the dynamic electrophoresis of a sphere in a spherical cavity is discussed as are the effects of the key factors on the phenomenon under consideration, which include the thickness of the double layer, the frequency of the applied electric field, the ratio of particle radius to cavity radius, and the boundary conditions of the surfaces of the particle and the cavity. The results of numerical simulation reveal that these key factors can have both quantitative and qualitative influence on the electrophoretic behavior of the particle. As an example, for the case of a positively charged particle placed in a negatively charged cavity if the double layer surrounding the particle is thin, the magnitude of the electrophoretic mobility of the particle increases with an increase in the frequency of the applied electric field and a phase lead may occur, but the opposite is true if the double layer is thick. These effects are not observed for the case of a positively charged particle placed in an uncharged cavity or for a positively charged particle placed in a positively charged cavity.

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PubMed2003

Electrophoresis in a non-Newtonian fluid: sphere in a spherical cavity.

The electrophoretic behavior of a sphere in a non-Newtonian fluid is investigated theoretically by analyzing the phenomenon that occurs in a spherical cavity under the condition of a weak applied electrical field. Non-Newtonian behavior in the liquid phase may be due to, for example, the addition of polymer to a colloidal dispersion to improve its stability. It may also arise from the increase in the volume fraction of the dispersed phase such as the slurry used in chemical mechanical polishing. A Carreau model is adopted to characterize the shear-thinning behavior of the liquid phase. We show that the difference between the mobility of the particle based on the present model and that based on the corresponding Newtonian fluid increases with the decrease in the thickness of a double layer. The shear-thinning nature of the liquid phase has the effect of increasing the mobility.

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PubMed2003

Electrophoresis of concentrated mercury drops.

The electrophoretic behavior of concentrated monodispersed, positively charged mercury drops is investigated theoretically. The present study extends previous analyses by considering arbitrary surface potentials, double-layer polarization, and the interaction between adjacent double layers. The coupled equations describing the spatial variations in the flow field, the electric field, and the concentration field are solved by a pseudo-spectral method. For a low surface potential phi(r), the mobility increases monotonically with kappaalpha; kappa and alpha are respectively the reciprocal Debye length and the radius of a mercury drop. For medium and high phi(r), the mobility curve has a reflection point, which arises from the interaction of adjacent double layers, for kappaalpha. Also, if phi(r) is high, the mobility curve may exhibit a local minimum as kappaalpha varies. This phenomenon is pronounced if the concentration of the dispersed phase is high. If the double layer is thick, the mobility increases with phi(r), and the reverse is true if it is thin. We show that the higher the concentration of the dispersed phase the smaller the mobility, and as kappaalpha becomes large the mobility approaches a constant value, which is independent of the concentration of the dispersed phase. The mobility of mercury drops is larger than that of the corresponding rigid particles.

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PubMed2003

Fertility and taxon-specific sperm binding persist after replacement of mouse sperm receptors with human homologs.

The zona pellucida surrounding ovulated mouse eggs contains three glycoproteins, two of which (ZP2 and ZP3) are reported sperm receptors. After fertilization, the zona pellucida is modified ad minimus by cleavage of ZP2, and sperm no longer bind. Crosstaxa sperm binding is limited among mammals, and human sperm do not bind to mouse eggs. Using transgenesis to replace mouse ZP2 and/or ZP3 with human homologs, mouse lines with human-mouse chimeric zonae pellucidae have been established. Unexpectedly, mouse, but not human, sperm bind to huZP2 and huZP2/huZP3 rescue eggs, eggs fertilized in vitro with mouse sperm progress to two-cell embryos, and rescue mice are fertile. Also unanticipated, human ZP2 remains uncleaved after fertilization, and mouse sperm continue to bind early rescue embryos. These observations are consistent with a model in which the supramolecular structure of the zona pellucida necessary for sperm binding is modulated by the cleavage status of ZP2.

Animals↗

PubMed2002

Imprint control element-mediated secondary methylation imprints at the Igf2/H19 locus.

Understanding the molecular basis of monoallelic expression as observed at imprinted loci is helpful in understanding the mechanisms underlying epigenetic regulation. Genomic imprinting begins during gametogenesis with the establishment of epigenetic marks on the chromosomes such that paternal and maternal chromosomes are rendered distinct. During embryonic development, the primary imprint can lead to generation of secondary epigenetic modifications (secondary imprints) of the chromosomes. Eventually, either the primary imprints or the secondary imprints interfere with transcription, leading to parent-of-origin-dependent silencing of one of the two alleles. Here we investigated several aspects pertaining to the generation and functional necessity of secondary methylation imprints at the Igf2/H19 locus. At the H19 locus, these secondary imprints are, in fact, the signals mediating paternal chromosome-specific silencing of that gene. We first demonstrated that the H19 secondary methylation imprints are entirely stable through multiple cell divisions, even in the absence of the primary imprint. Second, we generated mouse mutations to determine which DNA sequences are important in mediating establishment and maintenance of the silent state of the paternal H19 allele. Finally, we analyzed the dependence of the methylation of Igf2DMR1 region on the primary methylation imprint about 90 kilobases away.

Animals↗

PubMed2002

Sedimentation of concentrated spherical particles with a charge-regulated surface.

The sedimentation of a concentrated colloidal dispersion is examined for the case of an arbitrary double-layer thickness. Here, a general mixed-type condition on particle surface is assumed, and the classic models, which assume constant surface properties, can be recovered as the special cases of the present analysis. In particular, the behavior of biological cells, which carry dissociable functional groups on their surfaces, and particles, which are capable of exchanging ions with the surrounding medium, can be simulated by the present model. The mixed-type boundary condition leads to several interesting results in both sedimentation velocity and sedimentation potential as double-layer thickness and the concentration of particles vary.

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PubMed2002

Dynamic electrophoretic mobility of a concentrated dispersion of particles with a charge-regulated surface at arbitrary potential.

The dynamic electrophoretic mobility of a concentrated dispersion of biocolloids such as cells and microorganisms is modeled theoretically. Here, a biological particle is simulated by a particle, the surface of which contains dissociable functional groups. The results derived provide basic theory for the quantification of the surface properties of a biocolloid through an electroacoustic device, which has the merit of making direct measurement on a concentrated dispersion without dilution. Two key parameters are defined to characterize the phenomenon under consideration: the first, A, is associated with the pH of the dispersion, and the second, B, is associated with the equilibrium constant of the dissociation reaction of the functional group. We show that if A is large and/or B is small, the surface potential is high, and the effect of double-layer polarization becomes significant. In this case the dynamic electrophoretic mobility may have a local maximum and a phase lead as the frequency of the applied electric field varies. Due to the hydrodynamic interaction between neighboring particles, the dynamic electrophoretic mobility decreases with the concentration of dispersion.

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PubMed2002

Electrophoresis of a concentrated spherical dispersion at arbitrary electrical potentials.

The electrophoretic behavior of a concentrated spherical dispersion is investigated theoretically. The present analysis extends those in the literature in that both the surface potential of a particle and the strength of the applied electric field are arbitrary and both the effects of double-layer polarization and the overlapping between neighboring double layers are taken into account. Results based on these conditions are highly desirable since they cover essentially all the possible experimental conditions in practice. We show that, for a fixed surface potential and strength of applied electric field, the higher the concentration of particle, the smaller the mobility. Counterions are found to accumulate at the downstream side of a particle. Double-layer polarization is inappreciable if either it is thick or the concentration of the particle is high.

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PubMed2002

Electrophoresis of a sphere normal to a plane at arbitrary electrical potential and double layer thickness.

The electrophoretic movement of a sphere normal to an uncharged, planar surface is analyzed theoretically, taking the effect of double layer polarization into account. Here, both the surface potential of the particle and the thickness of the double layer surrounding it can be arbitrary. We show that if double layer polarization is neglected, the effect of the surface potential of a particle on its electrophoretic velocity is inappreciable. On the contrary, it becomes significant if double layer polarization is present. However, if the distance between the particle and the surface is sufficiently close, since the hydrodynamic effect dominates, the influence of the surface potential and double layer polarization becomes insignificant.

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PubMed2002

Differential mechanical activation of mitogen-activated protein kinases in intact human blood vessels.

BACKGROUND: Vascular tissue remodels in response to a variety of hemodynamic factors, often transduced through activation of mitogen-activated protein kinases such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase (JNK). This study tests the hypothesis that these kinases are involved in mechanical signal transduction in intact human arteries and veins. METHODS: Unused portions of human saphenous vein and radial artery were obtained fresh at the time of peripheral or coronary bypass. A sample of the vessel was immediately snap frozen (control(0)) and the remainder separated into three segments. One segment was placed in sterile medium and left undisturbed for 2 h (control(2)), one was perfused with sterile medium for 2 h at a steady rate of 150 ml/min, yielding shear stress values of 8-20 dyne/cm(2) (flow), and one was statically pressurized without flow at 110 mm Hg for 2 h (pressure). After treatment, samples were tested for phosphorylated ERK1/2 and JNK using Western blot. RESULTS: Two hours of culture produced mild increases in ERK1/2 activity in both vessel types. Stimulation with continuous rapid flow produced significantly increased ERK1 activity and a nearly 100% increase in ERK2 in veins. Static pressurization also stimulated ERK1/2, although slightly less than continuous flow. ERK1/2 phosphorylation was only mildly increased in flow-stimulated radial arteries, and exposure to normal systemic pressure showed no appreciable effect. Significant phosphorylation of JNK was not observed in either vessel. CONCLUSION: ERK1/2 phosphorylation is increased in human saphenous veins and radial arteries exposed to the hemodynamic conditions of arterial grafting. This pathway may be involved in the transduction of external stimuli leading to remodeling.

Culture Media↗