Myeloperoxidase G-463A polymorphism and Alzheimer's disease in the ApoEurope study

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Epidemiological and molecular genetic studies have shown the existence of several genes associated with increased risk of AD, the major genetic susceptibility locus coding for apolipoprotein E (apoE). A polymorphism in the myeloperoxidase gene (MPO) has previously been associated with AD susceptibility. However, results in the literature are controversial and seem to be dependent on several factors such as gender, apoE polymorphism or the genetic structure of the population. We investigated MPO G-463A and apoE polymorphism in 265 cases and 246 controls from the ApoEurope Study. In females, we found a significant association between MPO genotype and AD (P=0.034), GG genotype frequency being lower in cases (52.4%) as compared to controls (64.2%). In men, there was no significant effect of MPO polymorphism. No interaction was found between MPO polymorphism and apoE epsilon 4 allele. In conclusion, the G-463A polymorphism of MPO was statistically associated with AD in a gender-specific manner. However, given the low significance of P value we suggest no causal effect of the MPO gene in AD, as also evidenced in a recent meta-analysis. Our results support the hypothesis of a possible linkage disequilibrium between the MPO G-463A gene polymorphism and another functional variant involved in AD.

Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter.

Aquaporin-4 (AQP4) has recently been implicated in the pathogenesis of neuromyelitis optica(NMO) where it has been identifed as the first defined autoantigen pertinent to an infammatory demyelinating disorder of the human CNS. Furthermore, a recent case report has shown a lack of AQP4 expression in the spinal cord lesions of NMO. However, the pattern of AQP4 expression in multiple sclerosis (MS) tissues has not been well-defned. In the present investigation we have confirmed a lack of expression of AQP4 in optic and spinal cord lesions in NMO which contrasted sharply with the increased levels of AQP4 expression seen in MS lesions. Furthermore a detailed immunohistochemical and semi-quantitative analysis is used to describe the expression pattern of AQP4 on well-characterized tissue microarray samples of MS and control white matter. Anatomically AQP4 was more highly expressed in all categories of MS tissue compared to normal control tissues with the most abundant expression in active lesions. Within active lesions AQP4 expression was significantly correlated with expression of the pro-infammatory cytokine osteopontin. At the cellular level dual-labelling immunofluoresence demonstrated that increased expression of AQP4 was most pronounced at the astrocytic endfeet but was also associated with the cell bodies of astrocytes in the tissue parenchyma. The finding of increased AQP4 expression in MS lesions in contrast to the lack of expression in NMO lesions may suggest different mechanisms of initiation and progression between the two disease states.

Element partitioning and potential mobility within surface dusts on buildings in a polluted urban environment, Budapest.

A voluminous literature exists on the analysis of water-soluble ions extracted from gypsum crusts and patinas formed on building surfaces. However, less data is available on the intermediate dust layer and the important role its complex matrix and constituents play in crust/patina formation. To address this issue, surface dust samples were collected from two buildings in the city of Budapest. Substrate properties, different pollution levels and environmental variations were considered by collecting samples from a city centre granite building exposed to intense traffic conditions and from an oolitic limestone church situated in a pedestrian area outside and high above the main pollution zone. Selective extraction examines both water-soluble ions (Ca2+, Mg2+, Na+, K+, Cl-, NO3- SO42-) and selected elements (Fe, Mn, Zn, Cu, Cr, Pb, Ni) from the water-soluble, exchangeable/carbonate, amorphous Mn, amorphous Fe/Mn, crystalline Fe/Mn, organic and residual phases, their mobility and potential to catalyse heterogeneous surface reactions. Salt weathering processes are highlighted by high concentrations of water-soluble Ca2+, Na+, Cl- and SO42-- at both sites. Manganese, Zn and Cu and to a lesser extent Pb and Ni, are very mobile in the city centre dust, where 30%, 54%, 38%, 11% and 11% of their totals are bound by the water-soluble phase, respectively. Church dust shows a sharp contrast for Mn, Zn, Cu and Pb with only 3%, 1%, 12% and 3% of their totals being bound by the water-soluble phase respectively. This may be due to (a) different environmental conditions at the church e.g. lower humidity (b) continuous replenishment of salts under intensive city centre traffic conditions (c) enrichment in oxidisable organic carbon by a factor of 4.5 and a tenfold increase in acidity in the city centre dust.

Post-depositional modification of atmospheric dust on a granite building in central Rio de Janeiro: implications for surface induration and subsequent stone decay

Extensive contour scaling of a 200 year old granite church is associated with the breaching of an apparently iron-rich crust and the widespread deposition of atmospheric dust within the canyon-like streetscape of Rio de Janeiro. Contemporary dust, accumulated dust from within the a depression on the building surface, the surface crust and the underlying granite are examined by a combination of total element analysis and sequential extraction, X-ray diffraction and energy dispersive X-ray fluorescence. Results indicate an increase in total organic carbon and a marked decrease in pH within the accumulated dust, and a rapid mobilization of anions and cations from the water-soluble and carbonate phases. It is considered that the latter is linked to salt accumulation within and eventual salt weathering of the granite. Post-depositional alteration of the dust is also linked with the de-silicification of clay minerals (Illite to kaolinite) and the loss of silica from the amorphous Fe/Mn phase of the accumulated dust under the initially saline and progressively more acidic conditions experienced at the stone - atmosphere interface. This mobilization of silica is associated with the formation of what is, in effect, a thin silica-rich surface crust or glaze. Within the glaze, assessory amounts of extractable iron are concentrated within the amorphous and crystalline Fe/Mn phases at levels that are significantly elevated with respect to the underlying granite, but much lower than the equivalent phases of the accumulated dust from which it is principally assumed to derive. The protection afforded to the stone work by the crust is not, however, permanent and within the last 15 years it has been possible to observe a rapid increase in the surface delamination of the church close to street level.

Sandstone response to salt weathering following simulated fire damage: a comparison of furnace heating and fire.

Fire has long been recognized as an agent of rock weathering. Our understanding of the impact of fire on stone comes either from early anecdotal evidence, or from more recent laboratory simulation studies, using furnaces to simulate the effects of fire. This paper suggests that knowledge derived from simulated heating experiments is based on the preconceptions of the experiment designer – when using a furnace to simulate fire, the operator decides on the maximum temperature and the duration of the experiment. These are key factors in determining the response of the stone to fire, and if these are removed from realworld observations then knowledge based on these simulations must be questioned. To explore the differences between heating sandstone in a furnace and a real fire, sample blocks of Peakmoor Sandstone were subjected to different stress histories in combination (lime rendering and removal, furnace heating or fire, frost and salt weathering). Block response to furnace heating and fire is discussed, with emphasis placed on the non-uniformity of the fire and of block response to fire in contrast to the uniform response to surface heating in a furnace. Subsequent response to salt weathering (by a 10% solution of sodium chloride and magnesium sulphate) was then monitored by weight loss. Blocks that had experienced fire showed a more unpredictable response to salt weathering than those that had undergone furnace heating – spalling of corners and rapid catastrophic weight loss were evidenced in blocks that had been subjected to fire, after periods of relative quiescence. An important physical side-effect of the fire was soot accumulation, which created a waxy, relatively impermeable layer on some blocks. This layer repelled water and hindered salt ingress, but eventually detached when salt, able to enter the substrate through more permeable areas, concentrated and crystallized behind it, resulting in rapid weight loss and accelerated decay. Copyright ©2007 John Wiley & Sons, Ltd.