Catherine Adams

Use of the radiation-inducible WAF1 promoter to drive iNOS gene therapy as a novel anti-cancer treatment.

Inducible nitric oxide synthase (iNOS) gene therapy has been identified as a potential anti‐tumour strategy. A major problem common to most gene therapy strategies is targeting of treatment to the tumour volume. In this study we report on the use of the X‐ray‐inducible WAF1 promoter to achieve targeting of iNOS expression to the tumour volume.

Nitric oxide synthase gene therapy enhances the toxicity of cisplatin in cancer cells

Nitric oxide (NO·) derived from donor drugs has been shown to be an effective chemosensitizer in vitro. We investigated the combination of inducible nitric oxide synthase (iNOS) gene transfer, driven by a strong constitutive promoter (cytomegalovirus; CMV) with the DNA cross‐linking agent cisplatin in mouse and human tumour cell lines.

Nitric Oxide Produced in Response to Engagement of beta 2 Integrins on Human Neutrophils Activates the Monomeric GTPases Rap1 and Rap2 and Promotes Adhesion

We found that engagement of β2 integrins on human neutrophils increased the levels of GTP-bound Rap1 and Rap2. Also, the activation of Rap1 was blocked by PP1, SU6656, LY294002, GF109203X, or BAPTA-AM, which indicates that the downstream signaling events in Rap1 activation involve Src tyrosine kinases, phosphoinositide 3-kinase, protein kinase C, and release of calcium. Surprisingly, the β2 integrin-induced activation of Rap2 was not regulated by any of the signaling pathways mentioned above. However, we identified nitric oxide as the signaling molecule involved in β2 integrin-induced activation of Rap1 and Rap2. This was illustrated by the fact that engagement of β2 integrins increased the production of nitrite, a stable end-product of nitric oxide. Furthermore, pretreatment of neutrophils with Nω-monomethyl-l-arginine, or 1400W, which are inhibitors of inducible nitric-oxide synthase, blocked β2 integrin-induced activation of Rap1 and Rap2. Similarly, Rp-8pCPT-cGMPS, an inhibitor of cGMP-dependent serine/threonine kinases, also blunted the β2 integrin-induced activation of Rap GTPases. Also nitric oxide production and its downstream activation of cGMP-dependent serine/threonine kinases were essential for proper neutrophil adhesion by β2 integrins. Thus, we made the novel findings that β2 integrin engagement on human neutrophils triggers production of nitric oxide and its downstream signaling is essential for activation of Rap GTPases and neutrophil adhesion.

Visualisation for increasing health intentions: Enhanced effects following a health message and when using a first-person perspective

The present research explored whether visualising engaging in a health behaviour resulted in increased intentions to engage in that behaviour, when combined with an informational health message. Further, the effects of the visual perspective (first-person vs. third-person) used to visualise the health behaviour were explored. In an online questionnaire study employing a 2 × 3 between-participants experimental design, participants (N = 532) read vs. did not read an informational health message about the benefits of increasing fruit consumption, then visualised (from first-person vs. third-person perspective) vs. did not visualise themselves increasing their fruit consumption. Intentions to increase fruit consumption were assessed, as were potential mediating variables. The results indicated that visualisation (irrespective of perspective) did not result in increased intentions when it was not combined with the health message. However, when participants had read the health message, visualisation resulted in significantly stronger intentions, and the first-person perspective was significantly more effective than the third-person perspective. The beneficial effect of visualisation, and the first-person perspective, on intentions was mediated by increased self-efficacy and action planning. Findings are discussed in relation to existing research on visualisation and perspective, and in terms of practical applications for health promotion efforts.

Do High Frequency Ultrasound Images Support Clinical Skin Assessment

High frequency ultrasound imaging has been reported as a potential method of identifying the suspected tissue damage in patients “at risk” of pressure ulceration. The aim of this study was to explore whether ultrasound images supported the clinical skin assessment in an inpatient population through identification of subcutaneous tissue damage. Skin on the heels and/or sacral coccygeal area of fifty vascular surgery inpatients was assessed clinically by tissue viability nurses and with ultrasound pre operatively and at least every other day until discharge. Images were compared to routine clinical skin assessment outcomes. Qualitative classification of ultrasound images did not match outcomes yielded through the clinical skin assessment. Images corresponding to 16 participants were classified as subgroup 3 damage at the heels (equivalent to grade 2 pressure ulceration); clinical skin assessment rated no heels as greater than grade 1a (blanching erythema). Conversely, all images captured of the sacral coccygeal area were classified as normal; the clinical skin assessment rated two participants as grade 1b (non-blanching erythema). Ultrasound imaging is a potentially useful adjunct to the clinical skin assessment in providing information about the underlying tissue. However, further longitudinal clinical assessment is required to characterise images against actual and “staged” pressure ulceration.

Visualising future behaviour: Effects for snacking on biscuit bars, but no effects for snacking on fruit

In this study, participants (N = 223) were randomised to visualise snacking on fruit, visualise snacking on biscuit bars or no visualisation, and intentions and attitudes towards fruit and biscuit bars, immediate selection of fruit or biscuit bars and subsequent consumption were measured. No effects of visualising snacking on fruit were found once background variables were taken into account. Visualising snacking on biscuit bars, however, resulted in greater intentions to consume biscuit bars (smallest β = 0.19, p < 0.01). These findings suggest that specifics of the visualised target behaviour may be important in visualisation. Further investigation is needed before recommending visualisation for increasing fruit consumption.