Differential expression of steroid 5 alpha-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

The biological role of steroid 5 alpha-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor beta 1 (TGFB1), endothelin (EDN1), TGF alpha (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 mu M). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors. Endocrine-Related Cancer (2010) 17 757-770

Parenting stress and children with cerebral palsy: A European cross-sectional survey

Aim
The aim of this study was to describe stress in the parents of children with cerebral palsy and investigate associations with very high stress.

Method
A cross-sectional survey was conducted of parents of 818 children aged 8 to 12 years from nine regions in Europe. Families were eligible to participate if they were living in one of the specified geographic areas. Parental stress was captured using the Parenting Stress Index Short Form, which has 36 items and takes 10 minutes to complete. Parents rate items on a 5-point Likert scale, with higher scores indicating higher stress. The Short Form yields scores on three subscales and a Total Stress score. A trained research associate administered the questionnaire in the child’s home and visits lasted 90 to 120 minutes. All data collected were reported by parents unless otherwise stated.

Results
The Total Stress score on the Parenting Stress Index was dichotomized into scores of less than 99 or 99 or more, the latter indicating ‘very high’ stress. Most respondents were mothers (94%), and 26% reported very high stress levels. The parents of children with communication impairment had higher odds for very high stress (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.2–3.0) than those whose child had no such impairment; the parents of children with moderate or severe pain had higher odds for very high stress (OR 1.7 [95% CI 1.1–2.4] and 2.5 [95% CI 1.5–4.3] respectively) than those whose child had no pain; and the parents of children with an intellectual impairment had higher odds for very high stress (OR 1.8; 95% CI 1.2–2.9) than those whose child had none. There was no association between very high stress and motor impairment. The subscales ‘parent–child dysfunctional interaction’ and ‘difficult child’ contributed most to the Total Stress score.

Interpretation
Parents of children with communication difficulties, intellectual impairment, or pain are at very high risk of stress. The final model explained 12% of the observed variation in very high stress.

Induction of endothelial PAS domain protein-1 by hypoxia: Characterization and comparison with hypoxia-inducible factor-1 alpha

Hypoxia results in adaptive changes in the transcription of a range of genes including erythropoietin. An important mediator is hypoxia-inducible factor-1 (HIF-1), a DNA binding complex shown to contain at least two basic helix-loop-helix PAS-domain (bHLH-PAS) proteins, HIF-1 alpha and aryl hydrocarbon nuclear receptor translocator (ARNT), In response to hypoxia, HIF-1 alpha is activated and accumulates rapidly in the cell. Endothelial PAS domain protein 1 (EPAS-1) is a recently identified bHLH-PAS protein with 48% identity to HIF-1 alpha, raising the question of its role in responses to hypoxia. We developed specific antibodies and studied expression and regulation of EPAS-1 mRNA and protein across a range of human cell lines. EPAS-1 was widely expressed, and strongly induced by hypoxia at the level of protein but not mRNA. Comparison of the effect of a range of activating and inhibitory stimuli showed striking similarities in the EPAS-1 and HIF-1 alpha responses. Although major differences were observed in the abundance of EPAS-1 and HIF-1 alpha in different cell types, differences in the inducible response were subtle with EPAS-1 protein being slightly more evident in normoxic and mildly hypoxic cells. Functional studies in a mutant cell line (Ka13) expressing neither HIF-1 alpha nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater EPAS-1 transactivation (relative to HIF-1 alpha transactivation) of the VEGF promoter than the LDH-A promoter. (C) 1998 by The American Society of Hematology.

Perceived relevance and foods with health-related claims

Although consumer perception of the health claims and nutrition information has been studied widely there is relatively little understanding about the motivational factors underpinning claim perception. The objective of this study is to investigate how levels of perceived relevance influence consumers’ responses to health claims that either promise to reduce a targeted disease risk or improve well-being in comparison to other types of health-related messages, and how attitudes towards nutritionally healthy eating, functional food and previous experience relating to products with health claims affect the consumers’ perceptions of nutrition and health claims. The data (N=2385) were collected by paper and pencil surveys in Finland, the UK, Germany and Italy on a target group of consumers over 35 year old, solely or jointly responsible for the family’s food shopping. The results showed that relevance has a strong influence on perceptions of personal benefit and willingness to buy products with health claims. However the impact of relevance is much stronger when the health risks are relevant to self than when it is relevant to those close to oneself, especially when the claim promises a targeted risk reduction with detailed information about function and health outcome. Previous experience with products with health claims and interest in nutritionally healthy eating promoted the utility of all claims, regardless of whether they were health or nutrition claims. However, to be influenced by health claims consumers also need to have a positive attitude towards functional food products.

An Introduction to the Special issue - Housing in Hard Times: Marginality, Inequality and Class, with Kim McKee

‘Housing in Hard Times’ was the theme of the Housing Studies Association annual conference in April 2011. The papers featured in this special issue are drawn from that conference. They examine the uneven impact of economic change on housing policy and related areas, with reference to conceptual ideas pertaining to urban marginality, inequality and class. Whilst the empirical focus of the papers is the UK, their intellectual contribution represents an attempt to ‘bring class back in’ to the housing studies literature and encourage more critical, theoretically informed scholarship.

Evaluation of hepatic changes and local and systemic immune responses in goats immunized with recombinant Peroxiredoxin (Prx) and challenged with Fasciola hepatica

Protection against Fasciola hepatica in goats immunized with Peroxiredoxin (Prx) was assessed. The experimental trial consisted of three groups of seven animals: group 1 were unimmunized and uninfected, group 2 were immunized with adjuvant only and group 3 were immunized with recombinant Prx in adjuvant (immunized and infected). Immunization with Prx in Quil A adjuvant, group 3, induced a reduction in fluke burden of 33.04% when compared to adjuvant control, group 2, although this difference was not significant. The hepatic gross and microscopical morphometric study revealed lower damage in the Prx-immunized compared to group 2 (p

Optical and near-infrared coverage of SN 2004et: physical parameters and comparison with other Type IIP supernovae

We present new optical and near-infrared (NIR) photometry and spectroscopy of the Type IIP supernova (SN), SN 2004et. In combination with already published data, this provides one of the most complete studies of optical and NIR data for any Type IIP SN from just after explosion to +500 d. The contribution of the NIR flux to the bolometric light curve is estimated to increase from 15 per cent at explosion to around 50 per cent at the end of the plateau and then declines to 40 per cent at 300 d. SN 2004et is one of the most luminous IIP SNe which has been well studied and characterized, and with a luminosity of log L = 42.3 erg s-1 and a 56Ni mass of 0.06 +/- 0.04 M-circle dot, it is two times brighter than SN 1999em. We provide parametrized bolometric corrections as a function of time since explosion for SN 2004et and three other IIP SNe that have extensive optical and NIR data. These can be used as templates for future events in optical and NIR surveys without full wavelength coverage. We compare the physical parameters of SN 2004et with those of other well-studied IIP SNe and find that the kinetic energies span a range of 1050-1051 erg. We compare the ejected masses calculated from hydrodynamic models with the progenitor masses and limits derived from pre-discovery images. Some of the ejected mass estimates are significantly higher than the progenitor mass estimates, with SN 2004et showing perhaps the most serious mass discrepancy. With the current models, it appears difficult to reconcile 100 d plateau lengths and high expansion velocities with the low ejected masses of 5-6 M-circle dot implied from 7-8 M-circle dot progenitors. The nebular phase is studied using very late-time Hubble Space Telescope photometry, along with optical and NIR spectroscopy. The light curve shows a clear flattening at 600 d in the optical and the NIR, which is likely due to the ejecta impacting on circumstellar material. We further show that the [O i] 6300, 6364 A line strengths in the nebular spectra of four Type IIP SNe imply ejected oxygen masses of 0.5-1.5 M-circle dot.

IONIC COMPOSITION OF THE LIVER FLUKE FASCIOLA-HEPATICA FROM DIFFERENT MAMMALIAN HOSTS AND COMPARISON WITH HOST BILE

A qualitative analysis of the cationic profile of bovine and ovine biles and of bovine, ovine and rat liver flukes has been carried out by DC are emission spectrography. A quantitative assessment of the concentrations of Na+, K+, Ca2+ and Mg2+ ions in bovine, ovine and rat flukes has been determined by atomic absorption spectrophotometry. The levels of these ions in bovine and ovine bile samples have also been assessed and compared with those of Hedon-Heig saline. The ionic composition of the two biles is similar and the concentration of each ion is greater than that in Hedon-Heig saline. Despite the similarity in biles, ion levels in bovine flukes are generally higher than those in ovine flukes. Ion levels in rat flukes are different again but show closer similarity to those in bovine, not ovine, flukes. The results are discussed in relation to the proposed operation of the osmoregulatory system in the fluke.