The mouth and dis/ability.

Our aims in this paper are threefold. First, to understand how the mouth reveals the kinds of human beings that are de/valued in specific national locations and in global discourses with special attention on disability. Second, to subject the mouth to analysis from critical disability studies, specifically, an approach we describe as dis/ability studies. Third, to ask how the mouth might work as a site of resistance for disabled people. The paper begins by providing an introduction to critical disability studies, a perspective that foregrounds disability as the primary focus for thinking through the ways in which the body and society are shaped together. We move in this literature review towards a dis/ability studies approach that recognises the simultaneous processes of disablism (the exclusion of people with impairments) and ableism (the system by which standards of human autonomy and capability are made as key indicators of human worth). We then analyse the mouth in relation to pathologisation, human enhancement and resistance. We conclude with some final thoughts on the offerings of a dis/ability studies approach to those of interested with the intersections of the mouth and society.

Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine, are expressed in human atherosclerotic lesions.

Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atherosclerotic lesions may play an important role in mononuclear cell recruitment and macrophage differentiation. We have analyzed the expression of the linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX(3)C chemokine fractalkine (CX(3)CL1) in primary macrophages and human atherosclerotic lesions by reverse transcription-polymerase chain reaction and immunohistochemistry. We show that macrophage expression of the chemokines MDC, fractalkine, and TARC is upregulated by treatment with the Th2-type cytokines interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalkine mRNA expression are seen in some, but not all, human arteries with advanced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalkine, and TARC are expressed by a subset of macrophages within regions of plaques that contain plaque microvessels. We conclude that MDC, fractalkine, and TARC, which are chromosome 16q13 chemokines, could play a role in mononuclear cell recruitment into atherosclerotic lesions and influence the subsequent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.

Scar management of cultured epithelial autograft.

Since the introduction of cultured epithelial autograft (CEA) for the treatment of burns wounds, the resulting scar has caused a great deal of concern. When CEA is applied to a deep wound the resulting scar is subject to breakdown with minimal trauma. It takes a considerable period of time, in some instances years, before the dermal-epidermal junction matures and the skin is able to endure the wear and tear of normal existence. Therefore it is understandable that the introduction of pressure garments for treating into these scars has been somewhat delayed. However, we believe that early aggressive pressure therapy is the treatment of choice in those cases where there is a strong chance of the scar becoming hypertrophic. This paper presents an approach to the problems of scar management with CEA, not only for the case of a major full-thickness burn, but also for a lesser burn injury. The concept of a hydrophobic fabric as a lining garment is introduced. The garment design has been changed, to pay particular attention to reduction of shearing forces and dissipation of pressure. The development of our hydrophobic pressure garment is beneficial as it both reduces surface maceration and shearing injury. Since it protects the fragile CEA, formal pressure management can be instituted early in the treatment programme.

Direct measurement of cutaneous pressures generated by pressure garments.

Pressure garments are the mainstay of burn scar management despite limited scientific evidence. This study demonstrates a simple method of directly measuring the cutaneous pressures generated by a pressure garment. The results show pressure garments generate an increase in subdermal pressures in the range 9-90 mmHg depending on the anatomical site. Garments over soft sites generate pressures ranging from 9 to 33 mmHg. Over bony prominences the pressures range from 47 to 90 mmHg. This method is believed to be more representative of the pressures generated than the interpositional techniques that measure garment-skin interface pressure, as it avoids garment distortion, the interference effect of the measurement device (size, conformation, area) and directly measures subdermal pressures. The method should be useful for larger research projects on pressure therapy and also for clinical management of pressure garments in the treatment of hypertrophic scar.

Anatomical variations in pressures generated by pressure garments.

Pressure therapy is the predominant means for prophylaxis and treatment of hypertrophic scar. Despite this, there is little scientific evidence to support its use. This study examines the pressures generated by pressure garments in four subjects at 36 different anatomical sites chosen to represent the varying body geometry. Direct subdermal pressures were measured by an established method, though novel for this application. Pressure garments create a mean increase in subdermal pressures of 22.2 mmHg (range -10 to 102 mmHg). A significant objective difference exists in pressures generated at different anatomical sites. These differences correlate to local tissue compliance and to known areas of good clinical response and inversely correlate to the radius of anatomic curvature. The data suggest that pressures around 15 mmHg are required to effect a positive scar response and that close experienced monitoring of garments be performed.

γ-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of ß-catenin.

Canonical Wnt signaling regulates the transcription of T-cell factor (TCF)-responsive genes through the stabilization and nuclear translocation of the transcriptional co-activator, ß-catenin. Overexpression of ß-catenin features prominently in acute myeloid leukemia (AML) and has previously been associated with poor clinical outcome. Overexpression of γ-catenin mRNA (a close homologue of ß-catenin) has also been reported in AML and has been linked to the pathogenesis of this disease, however, the relative roles of these catenins in leukemia remains unclear. Here we report that overexpression and aberrant nuclear localization of γ-catenin is frequent in AML. Significantly, γ-catenin expression was associated with ß-catenin stabilization and nuclear localization. Consistent with this, we found that ectopic γ-catenin expression promoted the stabilization and nuclear translocation of ß-catenin in leukemia cells. ß-Catenin knockdown demonstrated that both γ- and ß-catenin contribute to TCF-dependent transcription in leukemia cells. These data indicate that γ-catenin expression is a significant factor in the stabilization of ß-catenin in AML. We also show that although normal cells exclude nuclear translocation of both γ- and ß-catenin, this level of regulation is lost in the majority of AML patients and cell lines, which allow nuclear accumulation of these catenins and inappropriate TCF-dependent transcription.

OGG1 is a novel prognostic indicator in acute myeloid leukaemia.

OGG1 (8-oxoguanine DNA glycosylase) constitutes a key component of the DNA base excision repair pathway, catalysing the removal of 8-oxoguanine nucleotides from DNA, thereby suppressing mutagenesis and cell death. We found that OGG1 expression was significantly downregulated by the RUNX1-ETO fusion protein product of the t(8;21) chromosome translocation in normal haematopoietic progenitor cells and in patients with acute myeloid leukaemia (AML). Further examination of OGG1 expression in 174 AML trial patients using Affymetrix microarrays showed that the prevalence rate of OGG1 expression was 33% and correlated strongly with adverse cytogenetics. OGG1-expressing patients had a worse relapse-free survival and overall survival and an increased risk of relapse at 5-years of follow-up. There remained a trend towards increased relapse rate among OGG1-expressing patients, even after adjusting for other known risk factors in comprehensive stratified analyses. We also determined a trend for OGG1 expression to have a more adverse impact on disease outcome in the context of the FLT3-ITD mutation. This study highlights OGG1 as a valuable prognostic marker that could be used to sub-stratify AML patients to predict those likely to fail conventional chemotherapies but those likely to benefit from novel therapeutic approaches that modulate DNA repair activity.