No description available.

No description available.

No description available.

No description available.

No description available.

C3-antigen complexes induce B cell proliferation and the synthesis of specific antibodies in the immune response. The mechanism is understood to involve the co-ligation of antigen receptor (lgM) and CD21 on the membrane of antigen-specific B cells. CD23 is the low-affinity IgE receptor and also binds to CD21. It has been shown by NMR spectroscopy that the binding sites for IgE and CD21 on CD23 are distinct and nonoverlapping. CD23 is expressed as a homotrimer on the membrane of B cells and is cleaved by an endogenous metalloprotease to release soluble fragments that contain the f binding sites for both IgE and CD21. It is suggested that these fragments, like the C3antigen complexes, can co-ligate membrane IgE (mlgE) and CD21 on the surface of B cells to up-regulate IgE synthesis. This would enhance allergic responses in vivo. To test this hypothesis, a construct was generated to express a trimeric fragment of soluble human CD23 (LZ-CD23) and provide evidence for the protein's oligomeric state in solution using analytical ultracentrifugation. Surface plasmon resonance studies also showed that LZ-CD23 binds IgE with a high affinity. Confocal microscopy was used to demonstrate that LZ-CD23 caused the time-dependent re-distribution of fluorescentlylabelled mlgE and CD21 on human tonsillar B cells, stimulated with anti-CD40 and IL-4 to induce heavy-chain switching to 19B. As early as 15 minutes following incubation with LZ-CD23, rnIgE and CD21 were seen to co-cap in large aggregated clusters on the B cell surface. Additionally, the specificity of LZ-CD23 towards these markers was demonstrated as LZ-CD23 had no effect on the surface distribution of CD38. LZ-CD23 was shown to be biologically active by enhancing the secretion of IgE from B cells. Moreover, evidence is presented that CD23 exerts its IgE-potentiating action by specifically targeting cells that are pre-committed to 19B. The mechanism thus appears to resemble that of the C3-antigen complex in the immune response, except that it is isotype rather than antigen-specific. These results shed light on the role of CD23 in IgE homeostasis and suggest a novel means of targeting CD23 for intervention in the allergic response.

No description available.

No description available.

A review of the literature discussing the relationship between mechanical factors and osteoarthrosis (OA) is given. From this review, it is concluded that the impulsive loads experienced at heelstrike during normal level walking are associated with degeneration of the joints of the lower limb. The amount of loading experienced varies between individuals and it is proposed those with higher loading have a greater risk of developing OA. The apparatus and methods used to study the differences in heelstrike impulsive loading (HIL) in a subject population are described. The data from the gait studies is analysed using kinematic and kinetic models. The data confirms that the subject population consisted of two groups, one with a large HIL, the other with a small HIL. These differences are attributed to the kinematics of the swing leg, in particular the vertical velocity of the ankle at heelstrike. A two dimensional simulation model of the swing phase is developed. This model is used, together with an numerical technique, to change the swing phase pattern of a subject with a large HIL to that typical of a subject with a small HIL. The differences in joint moment between these two patterns is evaluated. A sagittal plane model of the patellofemoral joint is developed and described. This model is incorporated into an existing mathematical model of the lower limb. The lower limb model is used to evaluate the differences in muscular control effort required for the two swing phases described above. Differences are found in the phasing of the hip flexor muscles. It is concluded that changes in muscular phasic activity during early swing phase, combined with the dynamics of the swing leg, produce significant changes in the approach velocity of the ankle at heelstrike. Thus, the loading experienced at heelstrike is a function of the timing of muscle activity during swing phase and can be altered by training, so that preventative treatment of OA is possible.

Collagen plays an important role in many biological tissues, including skin, which, once dried and treated, forms parchment and leather. The structural alterations that occur in collagenous materials due to X-ray radiation damage, fluctuation of relative humidity, and mechanical deformation (with a special focus on historical parchment) are the focus of this thesis. The primary aim of this thesis is to investigate major structural changes to collagen within parchment when exposed to inappropriate levels of relative humidity during conservation treatments, and cyclic-humidity during long-term storage in archives, museums and libraries. This study led to the discovery that each parchment sample reacted to the application and removal of moisture in a different way, indicating the fundamental need to treat individual parchment documents as in-homogeneous materials. This thesis investigates the changes that fibrillar collagen undergoes and describes the creation of computational models capable of reproducing the X-ray diffraction patterns for collagen. Previous structural models have been created that sufficiently account for native collagen, however, models created as part of this thesis succeed where previous models have failed in explaining the X-ray diffraction patterns collected from damaged collagen. This study provided the opportunity to contribute towards a large-scale international collaborative project on the hugely important historical resource, the Domesday Book. X-ray diffraction was used to provide unprecedented analysis of Domesday Book samples, providing a structural survey at a molecular level. This analysis produced the conclusion that the majority of samples displayed the presence of collagen axial structure, and were generally of a degraded state as a consequence of the method used to source them the samples were scrapings from the surface, which was less intact than the bulk of the parchment.