Like other immune cells, natural killer (NK) cells show impaired effector functions in the microenvironment of tumors, but little is known on the underlying mechanisms. Since lactate acidosis, a hallmark of malignant tissue, was shown to contribute to suppression of effective antitumor immune responses, we investigated the impact of tissue pH and lactate concentration on NK‐cell functions in an aggressive model of endogenously arising B‐cell lymphoma. The progressive loss of IFN‐γ production by NK cells observed during development of this disease could be ascribed to decreased pH values and lactate accumulation in the microenvironment of growing tumors. Interestingly, IFN‐γ expression by lymphoma‐derived NK cells could be restored by transfer of these cells into a normal micromilieu. Likewise, systemic alkalization by oral delivery of bicarbonate to lymphoma‐developing mice was capable of enhancing IFN‐γ expression in NK cells and increasing the NK‐cell numbers in the lymphoid organs where tumors were growing. By contrast, NK‐cell cytotoxicity was dampened in vivo by tumor‐dependent mechanisms that seemed to be different from lactate acidosis and could not be restored in a normal milieu. Most importantly, alkalization and the concomitant IFN‐γ upregulation in NK cells were sufficient to significantly delay tumor growth without any other immunotherapy. This effect was strictly dependent on NK cells.
Ethanol extractable polyols and sugars from the dominant cryptogams of the Windmill Islands, Wilkes Land, East Antarctica, were characterized and quantified by gas liquid chromatography. Arabitol, ribitol and mannitol were the major low molecular weight carbohydrates extracted from all eight species of lichen analysed. Total extractable carbohydrate levels (20–60 mg g−1 dry weight) were comparable to those for temperate lichens. Extracts of four common bryophyte species were dominated by sucrose, glucose and fructose; little polyhydric alcohol was detected except in the liverwort Cephaloziella exiliflora which contained a substantial proportion of mannitol. Total carbohydrate levels in the bryophytes (9–60 mg g−1 dry weight) were comparable to those in lichens. The compositions of eight species of algae varied considerably. Prasiola crispa, Desmococcus vulgaris and Schizogonium murale possessed sorbitol as their main constituent and had extractable carbohydrate contents comparable to those found in bryophytes on a dry weight or chlorophyll a content basis. The one snow alga with comparable carbohydrate levels, Mesotaenium berggrenii, contained sucrose, glucose, glycerol and a number of unidentified compounds. The remaining four species (Oscillatoria sp., Chloromonas sp.1 and Chlorosarcina sp. 2 and Chlamydomonas pseudopulsatilla) did not accumulate comparable levels of sugars and polyols. Though the levels of these compounds were much lower in the Windmill Islands lichens than in maritime Antarctic species, their content with respect to water content (0.7–7 molal) was well above that at which cold acclimated plants accumulate these compounds (c. 100–500 millimolal), and which provide cryoprotection in vitro. In the case of the bryophytes and algae, however, the in vivo content was generally < 100 millimolal.
Despite routine monitoring and disinfection, treated swimming pools are frequently contaminated with the opportunistic pathogen Pseudomonas aeruginosa, which can represent a significant public health threat. This review was undertaken to identify the current understanding of risk factors associated with pool operation with respect to P. aeruginosa. The ecology and factors that promote growth of P. aeruginosa in the pool environment are complex and dynamic and so we applied a systematic risk assessment approach to integrate existing data, with the aim to improve pool management and safety. Sources of P. aeruginosa, types of infections, dose responses, routes of transmission, as well as the efficacy of current disinfectant treatments were reviewed. This review also highlights the critical knowledge gaps that are required for a more robust, quantitative risk assessment of P. aeruginosa. Quantitative risk management strategies have been successfully applied to drinking water systems and should similarly be amenable to developing a better understanding of the risk posed by P. aeruginosa in swimming pools.
Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single-hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management.
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