A longevity assurance gene homolog of tomato mediates resistance to Alternaria alternata f. sp. lycopersici toxins and fumonisin B1

The phytopathogenic fungus Alternaria alternata f. sp. lycopersici (AAL) produces toxins that are essential for pathogenicity of the fungus on tomato (Lycopersicon esculentum). AAL toxins and fumonisins of the unrelated fungus Fusarium moniliforme are sphinganine-analog mycotoxins (SAMs), which cause inhibition of sphingolipid biosynthesis in vitro and are toxic for some plant species and mammalian cell lines. Sphingolipids can be determinants in the proliferation or death of cells. We investigated the tomato Alternaria stem canker (Asc) locus, which mediates resistance to SAM-induced apoptosis. Until now, mycotoxin resistance of plants has been associated with detoxification and altered affinity or absence of the toxin targets. Here we show that SAM resistance of tomato is determined by Asc-1, a gene homologous to the yeast longevity assurance gene LAG1 and that susceptibility is associated with a mutant Asc-1. Because both sphingolipid synthesis and LAG1 facilitate endocytosis of glycosylphosphatidylinositol-anchored proteins in yeast, we propose a role for Asc-1 in a salvage mechanism of sphingolipid-depleted plant cells.     

Is caring the ethical ideal?

This paper will examine the claim that caring is an appropriate ethical ideal for nursing. Initially it will examine nursing's philosophy of care and caring, highlighting some areas of difficulty and dissatisfaction articulated by many of its contemporary theorists Evaluation of the notion of caring as an appropriate ethical ideal for nursing will be balanced against those in opposition, and in this process their critique will be discussed This discussion will focus on areas such as virtue, virtue ethics, moral responsibility, feminine values, mothering and the debate between male and female caring Different forms of caring will be evaluated and balanced against different forms of nursing The paper will then suggest that current views which hold aloft nursing as a bedmate of caring may be detrimental to both the cared-for and the carer, advocating in the process a move toward change     

Diversion of prostaglandin endoperoxide metabolism by selective inhibition of thromboxane A2 biosynthesis in lung, spleen or platelets.

Infusion of arachidonic acid through the guinea pig lung or the cat spleen causes a release of thromboxane A2 and prostaglandins, as measured by bioassay. After incubation of human platelets with arachidonate similar metabolites are formed, as demonstrated chromatographically. Infusion of imidazole (50-75 microgram/ml) through the lung or spleen specifically inhibits thromboxane A2 production and diverts the pathway to the prostaglandins, mainly prostaglandin F2alpha. In human platelets imidazole causes a dose-dependent inhibition of thromboxane A2 formation (ID50 5.5 X 10(-4) M). This inhibition is accompanied by a dose-dependent increase in prostaglandin F2alpha. Since thromboxane A2 induces platelet aggregation and is a potent vasoconstrictor, diversion of pathways to prostaglandins with opposite or less potent action might be of relevance in the treatment of cardiovascular diseases.     

Elicitation of allergic asthma by immunoglobulin free light chains

The observation that only 50% of patients with adult asthma manifest atopy indicates that other inflammatory mechanisms are likely involved in producing the characteristic features of this disorder; namely reversible airway obstruction, hyperresponsiveness, and pulmonary inflammation. Our recent discovery that antigen-specific Ig free light chains (LCs) mediate hypersensitivity-like responses suggests that these molecules may be of import in the pathophysiology of asthma. Using a murine experimental model of nonatopic asthma, we now have shown that an LC antagonist, the 9-mer peptide F991, can abrogate the development of airway obstruction, hyperresponsiveness, and pulmonary inflammation. Further, passive immunization with antigen-specific LCs and subsequent airway challenge can elicit a mast cell-dependent reaction leading to acute bronchoconstriction. These findings, and the demonstration that the concentration of free kappa LCs in the sera of patients with adult asthma were significantly increased (as compared with age-matched nonasthmatic individuals), provide previously undescribed insight into the pathogenesis of asthma. In addition, the ability to inhibit pharmacologically LC-induced mast cell activation provides a therapeutic means to prevent or ameliorate the adverse bronchopulmonary manifestations of this incapacitating disorder.     

Glutathione-conjugated toluene diisocyanate causes airway inflammation in sensitised mice

Toluene diisocyanate (TDI) is a highly volatile compound that reacts readily with nucleophilic compounds, sulfhydryl groups in particular. Since the epithelial lining fluid of the airways contains high levels of the sulfhydryl, glutathione (GSH), inhalation of TDI is likely to result in the formation of GS-TDI conjugates. We therefore investigated whether GS-TDI is capable of provoking irritant and/or allergic reactions. Irritant effects of GS-TDI were studied after intratracheal administration of a range of doses of GS-TDI in saline to naive BALB/c mice. GS-TDI caused a dose-dependent increase in neutrophils in the lungs 24 h after instillation. A dose equivalent to 150 g of TDI or lower had no effect. For provocation of allergic reactions, mice were sensitised by application of 1% TDI onto the skin on days 0 and 1, and challenged intratracheally with a sub-irritant dose of GS-TDI on day 8. GS-TDI did not induce non-specific tracheal hyperreactivity to carbachol 24 and 48 h after challenge in TDI-sensitised mice. However, it increased the numbers of neutrophils in the lungs as compared with the control mice. These findings suggest that GSH conjugation does not diminish the capacity of TDI to elicit irritant-induced inflammation in the lungs of mice at doses above 150 g of TDI in the conjugate. Moreover, the capacity to induce allergic-specific inflammation was retained at concentrations of GS-TDI being devoid of irritant activity. However, the GS-TDI conjugate failed to induce non-specific tracheal hyperreactivity. This may be the consequence of the deposition of excess of GSH upon local dissociation of the conjugate.     

Cost effectiveness of foldable multifocal intraocular lenses compared to foldable monofocal intraocular lenses for cataract surgery

AIM: To analyse the cost effectiveness of foldable monofocal intraocular lenses (IOLs) compared to foldable multifocal IOLs in cataract surgery alongside a prospective, multicentre randomised clinical trial (RCT). METHODS: Patients underwent cataract surgery with bilateral monofocal (n = 97) or multifocal (n = 93) IOL implantation. Cost data and patient preferences, using the visual analogue scale (VAS), the time trade-off (TTO), and the standard gamble (SG) technique were obtained preoperatively and postoperatively by structured interviews. The incremental costs (multifocal minus monofocal), mean costs per patient, and differences in preferences were computed. RESULTS: Mean costs for glasses per patient in the monofocal group were 41.67 and in the multifocal group 149.58. The difference in costs between the multifocal and monofocal group was -92.09 and was statistically significant (p = 0.008). No significant differences were found in total costs or in effectiveness between the monofocal and multifocal IOL group. CONCLUSION: The cost effectiveness of multifocal IOLs is reduced to a cost minimisation analysis, because of the inability to demonstrate significant differences in effects. The use of multifocal IOLs in cataract surgery resulted in a significant reduction in costs for patient's postoperative spectacles.     

Determinants of surgery related anxiety in cataract patients

BACKGROUND/AIMS: Not much is known about the relative importance of different determinants of anxiety in cataract patients. This study analysed the predictive value of factors related to surgery induced anxiety. METHODS: In 128 cataract patients, recruited from two hospitals (Medical Centre Maastricht Annadal (MCMA) and Rotterdam Eye Hospital (REH)), state anxiety was assessed at four different time points using the State-Trait Anxiety Inventory (STAI). The following predictive factors of anxiety were measured: trait anxiety, outcome expectancies, doctor-patient relationship, coping strategy, social support, information supply, sociodemographic variables, and previous cataract surgery. Repeated measures ANOVA, t tests, multiple regression analysis, and correlations were used to analyse data. RESULTS: In general patients reported little anxiety. The level of anxiety (scale 1-4) was the highest before surgery, decreased immediately after surgery, and increased again after the postoperative visit. Patients with higher trait anxiety levels (r = 0.41; p<0.01), and women (r = 0.30; p<0.01) reported more anxiety. The REH patients showed lower anxiety scores than the MCMA patients. CONCLUSION: Women and patients with higher trait anxiety were more likely to experience higher levels of state anxiety. Positive outcome expectancies and social support may decrease anxiety.     

Ca2+ sensors modulate asthmatic symptoms in an allergic model for asthma

We previously described two novel peptides, Ca2+-like peptide (CALP) 1 and CALP2, which interact with Ca2+-binding EF hand motifs, and therefore have the characteristics to define the role of the Ca2+-sensing regulatory protein calmodulin in asthma. In the present study, the effects of the calcium-like peptides were investigated in an animal model for allergic asthma. For that purpose, sensitized guinea pigs were intratracheally pretreated with CALP1 or CALP2. Thirty minutes later, the animals were challenged with aerosolized ovalbumin. Acute bronchoconstriction was measured as well as characteristic features of asthma 6 and 24 hours (h) after challenge. Neither CALP1 nor CALP2 prevented the anaphylactic response elicited by ovalbumin challenge. However, CALP1 pretreatment attenuated the influx of inflammatory cells in the lungs 6 h after challenge. Furthermore, radical production by these cells was diminished both 6 and 24 h after challenge. Moreover, CALP1 completely inhibited airway hyperresponsiveness in vitro 24 h after challenge. We conclude that CALP1, as a selective calmodulin agonist, inhibits the development of asthmatic features probably via the attenuation of mast cell degranulation and radical production. Specific modulation of calmodulin activity might therefore be a potential new target for the treatment of allergic asthma.