Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer's disease patients.

Here we show that fibroblasts from sporadic Alzheimer's disease (AD) patients specifically express an anomalous and detectable conformational state of p53 that makes these cells distinct from fibroblasts of age-matched non-AD subjects. In particular, we found that, in contrast to non-AD fibroblasts, p53 in AD fibroblasts is expressed at higher levels in resting condition, and presents a significant impairment of its DNA binding and transcriptional activity. All together, these findings figured out the presence of a mutant-like p53 phenotype. However, gene sequencing of the entire p53 gene from either AD or non-AD did not unravel point mutations. Based on immunoprecipitation studies with conformation-specific p53 antibodies (PAb1620 and PAb240), which discriminated folded versus unfolded p53 tertiary structure, we found that a significant amount of p53 assumed an unfolded tertiary structure in fibroblasts from AD patients. This conformational mutant-like p53 form was virtually undetectable in fibroblasts from non-AD patients. These data, independently from their relevance in understanding the etiopathogenesis of AD, might be useful for supporting AD diagnosis.

Prevention of latex allergy among health care workers: evaluation of the extractable latex protein content in different types of medical gloves.

BACKGROUND: Since the 1980s, there has been increased use of latex gloves by health care workers and a concomitant increase of irritant and allergic reactions. The total protein content and the latex allergenic protein content in different types of medical gloves commonly used in our hospital were evaluated to acquire information useful for preventing latex allergy in our hospital personnel. METHODS: The total protein content and the allergic latex protein contents were evaluated with Lowry modified method and RAST inhibition assay in samples and extracts of 29 different types of medical gloves. RESULTS: The highest concentrations of total proteins and allergenic latex proteins were found in examination powdered latex gloves and in surgical powdered latex gloves; a significant amount of latex proteins was found in some brands of nitrile gloves. CONCLUSIONS: The clear association between the total protein levels and the allergenic latex protein levels suggests that the gloves with highest total protein content have the greatest allergenic potential. Therefore, it is recommended that manufacturing companies should provide package inserts including the total protein contents and possibly allergenic latex protein levels. They should declare whether they have added latex to their nitrile glove formulation. RAST-inhibition assays directly on glove samples instead of glove extract seems to be a good reliable and faster alternative for the evaluation of the allergenic potential of latex gloves.

Selective impairment of p53-mediated cell death in fibroblasts from sporadic Alzheimer's disease patients.

In this study, we evaluated the response of different human skin fibroblast cultures obtained from eight probable Alzheimer's disease patients and eight non-Alzheimer's disease subjects to an acute oxidative injury elicited by H(2)O(2). This treatment generates reactive oxygen species, which are responsible for DNA damage and apoptosis. To compare the sensitivity of fibroblasts from Alzheimer's disease or non-Alzheimer's disease patients to H(2)O(2) exposure, we evaluated different parameters, including cell viability, the extension of DNA damage and the ability of the cells to arrest proliferation and to activate an apoptotic program. We found that fibroblasts from Alzheimer's disease patients were more resistant that those from control subjects to H(2)O(2) treatment, although the extent of DNA damage induced by the oxidative injury was similar in both experimental groups. The protective mechanism of Alzheimer's disease fibroblasts was related to an impairment of H(2)O(2)-induced cell cycle arrest and characterized by an accelerated re-entry into the cell cycle and a diminished induction of apoptosis. Fibroblasts from Alzheimer's disease patients also have a profound impairment in the H(2)O(2)-activated, p53-dependent pathway, which results in a lack of activation of p53 or p53-target genes, including p21, GADD45 and bax. This study demonstrates a specific alteration of an intracellular pathway involved in sensing and repairing DNA damage in peripheral cells from Alzheimer's disease patients.