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James B Phillips

Publications and source records attributed to James B Phillips.

5 recordsLinked to original sources

Characterization of a "blanch-blush" mechano-response in palmar skin.

Palmar finger skin reacts to extension under mechanical load -- blanching over proximal (intercrease skin, ICS) and middle phalanges, while blushing in crease skin (CS), which we have called the Blanch-Blush Reaction (BBR). The idea that the BBR is a result of surface capillary blood flow changes that relate to predictable deformation of aligned collagen matrices under applied uniaxial loads was tested. Nondestructive techniques, digital image analysis (DIA), laser Doppler scanning, and elastic scatter spectroscopy (ESS) were used to measure color and blood flow changes in healthy fingers when at rest and extended. Skin strain increased directly with applied load and DIA identified blanching (loss of redness) in the ICS, reflected by a decrease in hemoglobin (by ESS). Laser Doppler flowmetry identified an increase in blood flow in the CS zone on extension, with a minor increase in blood flow in the ICS zone, apparently due to diversion of flow to deeper vessels, when monitored by this technique. These changes correlated with the BBR, owing to altered capillary flow in the ICS and CS. The histology of orientation of collagen fibers and vessels in the two zones was consistent with this mechanism. This study demonstrates the interdependence between matrix orientation, applied load, and flow. It represents an elegant demonstration of collagenous tissue function through an everyday tissue reaction, which has not been described previously.

Adult↗

Fluid shear in viscous fibronectin gels allows aggregation of fibrous materials for CNS tissue engineering.

Fibronectin (Fn) materials prepared from human plasma have been used in various forms as substrates for tissue engineering. Such purposes require that the soluble protein aggregates into insoluble fibrous structures which encourage the attachment and migration of cells. The method of aggregation due to mechanical shear was investigated by applying fluid shear forces directly to a viscous solution of Fn. Structural analysis revealed that mechanical shear resulted in the formation of an orientated fibrous protein material that was less soluble than its non-sheared counterpart. The suitability of this shear aggregated Fn material for CNS repair purposes was assessed in vitro where it supported the growth of fibroblasts, S100 immunoreactive Schwann cells and GFAP immunoreactive astrocytes. Implantation of the shear aggregated Fn material into a rat model of spinal cord injury provided a permissive environment for axonal growth. This was extended using an impermeable coating to improve orientation and straightness of axonal growth.

Animals↗

Investigating mechanical behaviour at a core-sheath interface in peripheral nerve.

As peripheral nerves bend and stretch, internal elements need to move in relation to each other. However, the way in which intraneural components interact is poorly understood. Previous work identified a distinct core and sheath in the rat sciatic nerve and provides a useful model with which to investigate this interaction. Here we have focused on identifying the mechanical and anatomical characteristics of the interface between core and sheath. Nerve samples, 15 and 20 mm long, of rat sciatic nerves were harvested and placed in a purpose-built jig, and a tensile testing machine was used to pull core from sheath. Mechanical tests of specimens in which core had been previously pulled from sheath by 25% of its initial length achieved a mean pull-out force approximately six times smaller than that achieved using intact controls. These results are consistent with the proposal that core-sheath interactions involve physical connections rather than a viscous fluid interface. Anatomical features of this interface were characterised using transmission electron microscopy. It appeared that sheath was derived from epineurium and most of the perineurium, whilst core consisted of endoneurium and a small proportion of the perineurium: the plane of cleavage appeared to involve the innermost perineurial cell layer.

Animals↗

Among 46 near full length HIV type 1 genome sequences from Rakai District, Uganda, subtype D and AD recombinants predominate.

The impact of HIV-1 genetic diversity on candidate vaccines is uncertain. To minimize genetic diversity in the evaluation of HIV-1 vaccines, vaccine products must be matched to the predominant subtype in a vaccine cohort. To that end, full genome sequencing was used to detect and characterize HIV-1 subtypes and recombinant strains from individuals in Rakai District, Uganda. DNA extracted from peripheral blood mononuclear cells (PMBC) was PCR amplified using primers in the long terminal repeats (LTRs) to generate nearly full length genomes. Amplicons were directly sequenced with dye terminators and automated sequencers. Sequences were phylogenetically analyzed and recombinants were detected and mapped with distance scan and bootscan. Among 46 sequences, 54% were subtype D, 15% were subtype A, and 30% were recombinant. All recombinants were individually unique, and most combined subtypes A and D. Subtype D comprised more than 70% of all the HIV-1 genomes in Rakai when both pure subtypes and recombinants were considered. Candidate vaccines based on HIV-1 subtype D would be appropriate for evaluation in Rakai District, Uganda.

Adolescent↗

Neural tissue engineering: a self-organizing collagen guidance conduit.

We report a novel implantable device that will deliver a tethered aligned collagen guidance conduit containing Schwann cells into a peripheral nerve injury site. Cells (Schwann cells and fibroblasts) incorporated into tethered rectangular collagen gels contracted and resulted in uniaxial alignment. This tissue-engineered construct was tested in three-dimensional culture and demonstrated the ability to guide neurite extension from dissociated dorsal root ganglia. A silicone tube was adapted to provide tethering sites for an implantable construct such that uniaxial cell-generated tension resulted in the formation of a bridge of aligned collagen fibrils, with a resident Schwann cell population. The potential of this device for surgical nerve regeneration was assessed in a 5-mm defect in a rat sciatic nerve model. Neural regeneration through this device was significantly greater than in controls, demonstrating that this system has potential both as a simple robust clinical implant and as a three-dimensional engineered tissue model.

Animals↗