Magnetic resonance (MR) imaging with a whole-body imager was performed in 10 fresh, unfixed whole human brains selected randomly from cadavers. All subjects were neurologically intact before death. T2 time constants were measured within the caudate nucleus, putamen, globus pallidus, cortical gray matter, subcortical white matter, and optic radiation. These regions were then excised, and T2 values were measured again with a 1.5-T MR spectrometer. Quantitative assays of iron, ferritin, and protein from these areas were then performed. Iron concentration varied significantly among brain regions, whereas ferritin and protein concentrations were constant among brain regions and among individuals. Neither iron nor ferritin concentration showed any consistent correlation with T2 values. Histologic examination of brain micro-sections with iron- and ferritin-specific stains of demonstrated poor correlation with biochemical assays of ferritin and iron concentrations. Results indicate that T2 values correlate poorly with iron and ferritin concentrations found in neurologically intact brains.
In the past decade, growing public concern about novel technologies with uncertain potential long-term impacts on the environment and human health has moved risk policies toward a more precautionary approach. Focusing on mobile telephony, the effects of precautionary information on risk perception were analyzed. A pooled multinational experimental study based on a 5 × 2 × 2 factorial design was conducted in nine countries. The first factor refers to whether or not information on different types of precautionary measures was present, the second factor to the framing of the precautionary information, and the third factor to the order in which cell phones and base stations were rated by the study participants. The data analysis on the country level indicates different effects. The main hypothesis that informing about precautionary measures results in increased risk perceptions found only partial support in the data. The effects are weaker, both in terms of the effect size and the frequency of significant effects, across the various precautionary information formats used in the experiment. Nevertheless, our findings do not support the assumption that informing people about implemented precautionary measures will decrease public concerns.
The brain is the most compartmentalized organ. It is also highly aerobic. Because nerve cells grow but do not regenerate, the brain is the organ best suited for the accumulation of metabolic errors colocalized in specific areas of the brain over an extended period. Alzheimer's disease (AD) is primarily a neurological disorder of the elderly. It is suggested that this disorder results from the accumulation of such errors, and that AD onset aluminum and iron contribute to but do not necessarily initiate the onset of the disease. In vitro and in vivo evidence summarized here suggests that this is effected by interfering in the utilization of glucose and glucose-6-phosphate, and sequestration of iron by ferritin. 3,Bamyloid precursor proteins (3,-APPs) are normal components of the human brain and some other tissues. Proteolysis of these, presumably by serine proteases, generates a 39 to 42 amino acid long peptide, the a-amyloid (f,-AP). In AD brains, ,B-AP aggregates into plaque, the hallmark of AD brains. Some of the a-APPs also contain a 56 amino acid long segment which inhibits serine proteases. We show that in vitro, at pH 6.5, aluminum activates ,Bchymotrypsin 2-fold and makes it dramatically resistant to protease inhibitors such as bovine pancreatic trypsin inhibitor (bPTI) or its mimic present in the fVamyloid precursor proteins (,B-APPs). Iron and oxygen are reported to favor cross-linking of ,-AP in vitro. Because iron and ferritin are components of neurotic plaques, and acidic pH are reported in AD brains, we suggest that deregulation of iron and aluminum homeostasis permit their colocalization, and contribute to the accumulation of metabolic errors leading to neuronal disorders including the formation of AD (senile) plaques. -Environ Health Perspect 102(Suppl 3): 207-213 (1994)
The brain of Alzheimer disease patients contains plaques that are diagnostic for the disease. The plaques also contain (-amyloid peptide, a1-antichymotrypsin, and the element aluminum. We present indirect evidence that can relate all three components of plaques to each other in such a way as to suggest their involvement in the etiology of the disease. The P-amyloid peptide is derived by proteolytic processing from 3-amyloid precursor proteins and some of these proteins contain a domain that is highly homologous to bovine pancreatic trypsin inhibitor. Bovine pancreatic trypsin inhibitor also inhibits a-chymotrypsin and we show that aluminum affects both the activity and the inhibition ofthis enzyme. At pH 6.5, in the presence of aluminum, the enzyme activity is doubled, and the inhibitor is only 1% as effective as in the absence of the metal ion. The inhibition by BX-9, a protease inhibitor prepared from protein components of amyloid plaques, is also reduced by aluminum; so too is that by ar-antichymotrypsin but to a lesser degree. In the Alzheimer brain, we propose that aluminum may accelerate proteolytic processing of the P-amyloid precursor protein by suppression of the inhibitor domain. Thus, the 8-amyloid peptide may accumulate and initiate plaque formation.Increased levels of aluminum have been observed in neuritic deposits, the plaques and the neurofibrillary tangles, of Alzheimer disease (AD) (1) and amyotrophic lateral sclerosis (2). Several in vitro studies have demonstrated the neurotoxicity of aluminum (3). Recent epidemiological evidence associates increased bioavailability ofaluminum with incidence of AD (4). Because the solution chemistries of aluminum and iron are very similar (5), the observed slow accumulation of aluminum in brain and bone tissue is suggested to occur via the iron transport and storage systems (3). Despite the in vivo and in vitro evidence, no initial event(s) for the involvement of aluminum in AD or amyotrophic lateral sclerosis has been established. Therefore, some researchers have questioned (35) the importance or the role of aluminum in the early pathogenesis of these neurological disorders.By contrast, the /3-amyloid peptide found at the "heart" of AD plaques remains a consistent feature ofAD (6, 7). Recent discoveries of B-amyloid mutations in some cases of earlyonset familial AD further underscore the importance of 3-amyloid peptide in the etiology of AD (8). The P-amyloid peptide(s) has 39-43 amino acids and is part of the family of 3-amyloid precursor proteins that contain 695, 751, and 770 amino acids that upon proteolysis generate the 83-amyloid peptide(s). The two larger precursors (751 and 770 amino acids long) also contain a 56-amino acid segment whose sequence is >60% homologous to the bovine pancreatic trypsin inhibitor (bPJI). This discovery suggested the possible role ofthe inhibitor segment in regulating the proteolytic processing of the precursor proteins to generate f3-amyloid peptide(s). However, the pool of f3-amyloid protein precursors is neither ...
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