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Eukaryotic microorganisms are constantly challenged by reactive oxygen species derived endogenously or encountered in their environment. Such adversity is particularly applied to Saccharomyces cerevisiae under harsh industrial conditions. One of the major oxidants to challenge S. cerevisiae is linoleic acid hydroperoxide (LoaOOH). This study, which used genome-wide microarray analysis in conjunction with deletion mutant screening, uncovered the molecular pathways of S. cerevisiae that were altered by an arresting concentration of LoaOOH (75 μM). The oxidative stress response, iron homeostasis, detoxification through PDR transport and direct lipid β-oxidation were evident through the induction of the genes encoding for peroxiredoxins (GPX2, TSA2), the NADPH:oxidoreductase (OYE3), iron uptake (FIT2, ARN2, FET3), PDR transporters (PDR5, PDR15, SNQ2) and β-oxidation machinery (FAA2, POX1). Further, we discovered that Gpx3p, the dual redox sensor and peroxidase, is required for protection against LoaOOH, indicated by the sensitivity of gpx3Δ to a mild dose of LoaOOH (37.5 μM). Deletion of GPX3 conferred a greater sensitivity to LoaOOH than the loss of its signalling partner YAP1. Deletion of either of the iron homeostasis regulators AFT1 or AFT2 also resulted in sensitivity to LoaOOH. These novel findings for Gpx3p, Aft1p and Aft2p point to their distinct roles in response to the lipid peroxide. Finally, the expression of 89 previously uncharacterised genes was significantly altered against LoaOOH, which will contribute to their eventual annotation.

Elemental uptake and export of the cell are tightly regulated thereby maintaining the ionomic homeostasis. This equilibrium can be disrupted upon exposure to exogenous reactive oxygen species (ROS), leading to reduction or elevation of the intracellular metal ions. In this study, the ionomic composition in the eukaryotic model organism Saccharomyces cerevisiae was profiled using the inductively-coupled plasma optical emission spectrometer (ICP-OES) following the treatment with individual ROS, including hydrogen peroxide, cumen hydroperoxide, linoleic acid hydroperoxide (LAH), the superoxide-generating agent menadione, the thiol-oxidising agent diamide [diazine-dicarboxylic acid-bis(dimethylamide)], dimedone and peroxynitrite. The findings demonstrated that different ROS resulted in distinct changes in cellular metal ions. Aluminium (Al(3+)) level rose up to 50-fold after the diamide treatment. Cellular potassium (K(+)) in LAH-treated cells was 26-fold less compared to the non-treated controls. The diamide-induced Al(3+) accumulation was further validated by the enhanced Al(3+) uptake along the time course and diamide doses. Pre-incubation of yeast with individual elements including iron, copper, manganese and magnesium failed to block diamide-induced Al(3+) uptake, suggesting Al(3+)-specific transporters could be involved in Al(3+) uptake. Furthermore, LAH-induced potassium depletion was validated by a rescue experiment in which addition of potassium increased yeast growth in LAH-containing media by 26% compared to LAH alone. Taken together, the data, for the first time, demonstrated the linkage between ionomic profiles and individual oxidative conditions.

This report describes a biological screening system to measure the antioxidant capacity of compounds using the oxidant-induced growth arrest response of Saccharomyces cerevisiae. Alternative methods using the nonphysiological free radical compounds such as diphenylpicrylhydrazyl and azinobis ethylbenzothiaziline-6-sulphonate (ABTS) only provide an indication of the ability of a compound to scavenge oxidants. In contrast, this yeast-based method can also measure the ability of a compound to induce cellular resistance to the damaging effects of oxidants. The screening assay was established against a panel of six physiologically relevant oxidants ranging from reactive oxygen species (hydrogen peroxide, cumene peroxide, linoleic acid hydroperoxide), to a superoxide-generating agent (menadione), reactive nitrogen species (peroxynitrite) and a thiol-oxidizing agent (diamide). The antioxidants ascorbate and gallic acid displayed scavenging activity and induced the resistance of cells against a broad range of oxidants using this assay. Lipoic acid, which showed no scavenging activity and thus would not be detected as an antioxidant using a nonphysiological screen was, however, identified in this assay as providing resistance to cells against a range of oxidants. This assay is high throughput, in the format of a 96-well microtitre plate, and will greatly facilitate the search for effective antioxidants.

Amino acid biosynthesis forms part of an integrated stress response against oxidants in Saccharomyces cerevisiae and higher eukaryotes. Here we show an essential protective role of the l-lysine biosynthesis pathway in response to the oxidative stress condition induced by the lipid oxidant-linoleic acid hydroperoxide (LoaOOH), by means of transcriptomic profiling and phenotypic analysis, and using the deletion mutant dal80∆ and lysine auxotroph lys1∆. A comprehensive up-regulation of lysine biosynthetic genes (LYS1, LYS2, LYS4, LYS9, LYS12, LYS20 and LYS21) was revealed in dal80Δ following the oxidant challenge. The lysine auxotroph (lys1∆) exhibited a significant decrease in growth compared with that of BY4743 upon exposure to LoaOOH, albeit with the sufficient provision of lysine in the medium. Furthermore, the growth of wild type BY4743 exposed to LoaOOH was also greatly reduced in lysine-deficient conditions, despite a full complement of lysine biosynthetic genes. Amino acid analysis of LoaOOH-treated yeast showed that the level of cellular lysine remained unchanged throughout oxidant challenge, suggesting that the induced lysine biosynthesis leads to a steady-state metabolism as compared to the untreated yeast cells. Together, these findings demonstrate that lysine availability and its biosynthesis pathway play an important role in protecting the cell from lipid peroxide-induced oxidative stress, which is directly related to understanding environmental stress and industrial yeast management in brewing, wine making and baking.

A common problem encountered in clinical medicine is the classification of a lung lesion (nodule/opacity) on conventional imaging. Often attempts at biopsy are unsuccessful or are falsely reassuring, and the decision to send the patient for more invasive and potentially morbid procedures can be difficult. Our aim was to investigate the role of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in helping to identify more accurately those patients with malignant lesions. Sixty-three patients underwent FDG-PET scans following unsuccessful biopsy of a lung lesion or, in a lesser number of cases, when an attempt at biopsy was considered too dangerous. Follow-up was by histology or, if this was unavailable, by clinical progress to death or a minimum of 18 months post scan. Visual and quantitative analysis was performed. On visual analysis, positive and negative predictive values were 90% and 100%, respectively. On quantitative (SUV2.5) analysis, positive and negative predictive values were 90% and 85%, respectively. We interpret these results as showing that the use of FDG-PET scans in patients in this circumstance is non-invasive and highly sensitive in diagnosing malignancy. The high positive predictive value suggests that those with a positive scan must undergo further investigation, while the 100% negative predictive value means those with no FDG uptake can safely be spared further invasive investigations

Needle localizations of radiologically suspicious but clinically impalpable breast lesions are being carried out with increasing frequency as a result of the National Breast Screening Programme. At our institution, the Nottingham Lesion Location Set (Mediplus Ltd, Bourne End, Bucks) has been used, without complication, for at least 50 such procedures (Fig. 1). It comprises an 18 gauge (G), or 21 G cannula, a fine needle localization wire which is fed through the cannula during initial positioning and a 20 G bluntended cannula which is introduced over the wire by the surgeon in theatre to facilitate identification of the wire tip. The following case report, undocumented to date, describes an unusual hazard of breast localization.

Exposure to solar radiation is increasingly being associated with a risk of cutaneous melanoma, and some risk has also been attributed to exposure to fluorescent lights. The risk of cutaneous melanoma associated with exposure to some sources of artificial ultraviolet radiation was examined in a case-control study in a Scottish population with fairly low exposure to natural ultraviolet radiation. The risk was not significantly or consistently raised for exposure to fluorescent lights at home or at work. The use of ultraviolet lamps and sunbeds, however, was associated with a significantly increased risk (relative risk = 2.9; 95% confidence interval 1.3 to 6.4), and the risk was significantly related to duration of use. The risk was particularly raised among people who have first used [corrected] ultraviolet beds or lamps more than [corrected] five years before presentation (relative risk = 9.1; 95% confidence intervals 2.0-40.6), in whom it was significantly related to cumulative hours of exposure. The risks associated with exposure to ultraviolet lamps and sunbeds remained significant after adjustment for other risk factors for melanoma.

A multicentre case-control study of 216 patients with palmoplantar pustulosis and 626 controls with miscellaneous dermatoses showed a considerably higher prevalence of smoking in the group with palmoplantar pustulosis. This was the first indication that smoking may be an important factor in this skin disease, possibly by affecting the inflammatory responses of the skin.

Enzyme preparations were isolated from post-mortem adrenal tissue of a patient with lipoid adrenal hyperplasia and normal human- and bovine adrenal tissue. Cholesterol-cleaving properties were studied in incubation experiments with the addition of appropriate substrates. Cholesterol-cleaving activity of enzyme preparations of adrenal tissue from the patient was extremely low as compared with normal controls. There was no difference in 20α-hydroxycholesterol-cleaving activity. There is thus evidence for a deficient 20α-cholesterol-hydroxylase activity in the adrenal tissue of this patient with lipoid adrenal hyperplasia.

The palatability of three bulk additives was studied in volunteers under 40 and over 60 years of age. Women highly significantly preferred Normaeol Special® (Norgine) to Fybogel® (Reckitt & Colman) and Celevac Granules® (W.B.P.). On both preference and palatability score Normacol Special was significantly preferred to Celevac Granules, as it was in the under 40's on palatability; score and in the over 60's on preference, but in the latter, sex may have accounted for the difference observed. Volunteers under the age of 40 gave Celevac a significantly higher palatability score than Fybogel; the reverse occurred in the over 60's. These results have therapeutic implications in patients with different gastrointestinal disorders.

Examination of 180 patients with cutaneous malignant melanoma and 197 control patients in a case-control study showed that the risk of melanoma is strongly related to numbers of benign melanocytic naevi (moles). Some unusual features of naevi--a diameter exceeding 7 mm, colour variation, and irregular lateral outline--also showed a strong association with the risk of melanoma, but the relation of numbers of naevi to risk was present even in the group of patients whose naevi had none of these unusual features. Biopsy of clinically atypical naevi from several of the patients at highest risk generally did not show dysplastic histology. Thus a group of people at high risk of melanoma may be identified by using simple clinical assessment of naevi.

In a study of risk factors for the development of melanocytic naevi in relation to the pathogenesis of malignant melanoma 197 white adults were examined by four dermatologists and naevus counts correlated with several other features. Highly significant associations were found between large numbers of banal acquired melanocytic naevi and the ability to tan easily without burning (skin types 3 and 4; relative risk 4.6), brown or hazel eyes (relative risk 3.5), green or grey eyes (relative risk 3.5) and brown or black hair (relative risk 3.7). No significant associations with numbers of naevi were shown for parity or use of oral contraceptives or other steroid hormones. This is the first study to find any relation between melanocytic naevi and phenotypic factors in a white population.

A case of hepatopulmonary hydatid disease in a Cypriot who presented with pyogenic infection with Streptococcus milleri is described. Although hydatid disease and pyogenic liver abscess are both rare in the UK, an underlying echinococcal pathology should be suspected in any patient from an area endemic for hydatid who presents with a pyogenic hepatic or hepatopulmonary abscess.