Proceedings: A nystatin-acid solid state interaction study.
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Biomedical subjects
Publications and source records attributed to M D Ward.
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Cell adhesion to substratum is often mediated by binding between cell surface receptors and substrate ligands. Substrates can be derivatized with different types and densities of ligands, but how substrate chemistry determines cellular function, such as adhesion strength, has not been demonstrated quantitatively. We employ a numerical methodology developed by Dembo and colleagues (9), who investigated membrane peeling under conditions of excess ligand density, to investigate the kinetics and strength of cell peeling from ligand coated surfaces for arbitrary ligand density. We show there are two asymptotic limits to peeling strength, as quantified by the critical tension: a high ligand density limit, where the critical tension is independent of ligand density and depends logarithmically on the receptor density; and a low ligand density limit, in which the critical tension depends logarithmically on the ligand density but is independent of receptor density. In between these limits, we numerically determine the critical tension. The critical tension is always a weak function of the dissociation constant between ligand and receptor. Furthermore, we show how the rate of peeling, for tensions above the critical tension, depends on ligand density and the mechanical properties of the receptor-ligand bonds. Interestingly, we illustrate when small increases in ligand density should alter cellular behavior, inducing a change to spreading onto a substrate from peeling up from a substrate. In total the predictions of this paper provide criteria for the design of ligand-coated substrate that provide for the proper adhesion strength and dynamics of detachment of cells from surfaces.
Many cell types modulate growth, differentiation, and motility through changes in cell substrate adhesion, including regulation of focal contact formation. Clustering of cell surface adhesion receptors is an essential early step in the development of focal contacts, and thus may influence cell physiology. In this paper, we present a theoretical framework to examine how cell surface chemistry affects receptor clustering. Our one-dimensional tape-peeling model couples the equations of mechanical equilibrium for a cell membrane with kinetic receptor-ligand binding relations. We considered two distinct model scenarios: Adhesion mediated by multiple receptor-ligand interactions of different length and specific binding of a single receptor type occurs in the presence of van der Waals attraction and nonspecific repulsion. In each case, nonuniform (wave-like) membrane morphologies are observed in certain parameter ranges that support the clustering of adhesion receptors. The formation of these morphologies is described in terms of a balance of membrane stresses; when cell-surface potential as a function of separation distance is symmetric between two potential energy minima, nonuniform morphologies are obtained. Increases in the chemical binding energy between receptor and ligand (e.g., increases in ligand density) or decreases in the membrane rigidity result in smaller wavelengths for nonuniform interfaces. Additionally, we show wave-like geometries appear only when the mechanical compliance of receptor-ligand bonds is within an intermediate range, and examine how the mobility of "repellers"--glycocalyx molecules that exert a nonspecific repulsive force--influences membrane morphology. We find fully mobile repellers always redistribute to prevent nonuniform morphologies.
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An in situ technique based on the mass-sensitive piezoelectric quartz crystal microbalance (QCM) was applied to continuously monitor the attachment and detachment of anchorage-dependent mammalian cells on a metal surface. Specifically, we have demonstrated that the attachment of Vero cells to metal surfaces on the piezoelectrically active area of the QCM results in decreases in the QCM resonant frequency that can be monitored conveniently in real time. Lysis and detachment of Vero cells caused by vesicular stomatitis virus (VSV) infection can also be monitored readily. Our results demonstrate that the QCM is a viable technique for monitoring anchorage-dependent cell attachment and detachment on surfaces (caused by stimulatory, inhibitory, or cytopathic effects).
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The nucleoprotein (NP) of Newcastle disease virus (NDV) was selected to study the relative importance of an internal structural protein in the avian immune response. The NP gene of the virulent, neurotropic NDV Texas GB (TGB) strain was cloned and sequenced. Nucleotide sequence data for the NP gene allowed comparison of the deduced amino acid sequences for the NP genes of NDV-TGB and the avirulent duck isolate NDV-D26. These comparisons demonstrated an 89% nucleotide sequence homology and a 97% homology between the deduced amino acid sequences. The NDV-TGB NP expressed in recombinant vaccinia virus (rVAC) was electrophoretically and immunologically identical to the wild-type NDV-TGB. Although inoculation of chickens with the recombinant vaccinia virus expressing the NDV NP gene elicited anti-NDV antibodies in higher titers than in birds inoculated with live LaSota NDV, this strong anti-NDV response did not protect against lethal challenge with NDV-TGB.
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Student rights and the responsibility of educators in providing adequate protection of those rights continues to be a major concern in all educational programs. Due process of law, as it pertains to the schools, outlines specific procedures that should be followed when disciplinary action must be taken involving a student. Applying these guidelines assures fundamental fairness and reasonableness.
The fluoroscopic double-contrast technique of arthrography of the knee is useful in documenting the extent of suspected injury to the knee. It is of particular value in demonstrating small and large lesions involving the menisci, cruciate ligaments, patellar cartilages, as well as the articular cartilages of the femoral condyles and tibial plateaus. This examination is instrumental in the diagnosis of the patient with an atypical history of injury and unusual physical findings. A simple restraint device allows the fluoroscopist complete control over the stress applied to the knee while positioning the patient for filming. Fluoroscopic spot radiographs of excellent contrast and sharp detail can be obtained of each of the various structures, applying the stress needed. When the radiologic technologist takes a little time to become more knowledgeable about the anatomy of the knee jount, and the rationale for the various views, the knee arthrographic examination is easily understood.