A comparative study in Alzheimer's and normal brains of trace element distribution using PIXE and INA analyses and glucose metabolism by positron emission tomography.

The onset of Alzheimer's disease has been shown to affect trace element concentrations in the brain when compared to "normal" subjects in ex vivo samples. The techniques used to determine trace element concentrations were proton-induced X-ray emission and instrumental neutron activation analysis. With these methods, significant differences are seen between lobes within a hemisphere and between the same lobes of opposing hemispheres for "normal" brains. The change observed in trace element concentrations may indicate a possible alteration in the function of the blood-brain barrier, the effect of which can be investigated in vivo using the imaging technique of positron emission tomography (PET). A PET study was performed on nine female and nine male subjects to determine whether the regional metabolic rate of glucose (rCMRGlu) varied between hemispheres and sex in the Alzheimer diseased brain as was seen in the trace element study. Glucose metabolism was measured using [F-18]-fluorodeoxyglucose (18F-FDG). Hemispherical differences were observed for the frontal, occipital, parietal lobes, and the temporolateral region in both males and females for rCMRGlu. Variation was also seen between sexes, where the frontal lobe had a lower rCMRGlu in females compared to that of males.

Major and trace element concentration differences between the right and left hemispheres of the "normal' human brain.

The brain can be divided into many anatomical regions, and the minor and trace element distribution across these regions has been shown to be heterogeneous. The various functions of the brain such as memory and language have been associated with different brain regions, and attempts to correlate brain function with elemental composition have been made. Establishing "normal" concentration values is a complex task due to the variability of factors such as age, sex, dietary intake, environmental exposure, and smoking habits. In establishing the elemental concentration of a particular brain region, a mean value from the right and left hemispheres of different brains is often used. This is usually due to the lack of availability for analysis of the same brain regions from both hemispheres of one individual. However, it is known that the right and left hemispheres have different functions. Thus, it may be expected that they may have different trace element concentrations as well. In this study 13 brain regions were sampled from both hemispheres of six elderly individuals, and their major element composition was determined by Rutherford backscattering (RBS) analysis, whereas the minor and trace element concentrations were obtained by particle induced X-ray emission (PIXE) analysis.

Two-dimensional gel analysis of histones in acid extracts of nuclei, cells, and tissues.

Two-dimensional gel analysis of histones from extracts of nuclei, cells, and tissues is described. A discontinuous buffer system concentrates the sample was used to increase resolution in both dimensions and also to allow the direct loading of HCl extracts of chromatin, nuclei, cells, and tissues. Stained one-dimensional gels are used as sample gels for the second dimension, cetylltrimethylammonium bromide being used to solubilize the proteins in the dye-protein complex. These methods enable one to purify proteins through acetic acid/urea/Triton, acetic acid/urea, and sodium dodecyl sulfate gels without eluting them from the gels. The method is also compatible with the use of protamine to displace histones from nuclei and nucleosomes separated in chromatin gels.

Histone 1 is proximal to histone 2A and to A24.

Water-soluble carbodiimide crosslinks histones 1A and 1B to histone 2A and to semi-histone A24 in chromatin from mouse cells. The identities of the histone species present in the crosslinked dimers were determined by fingerprinting. The molar ratio of H1--A24 to H2A is the same as the molar ratio of A24 to H2A in these cells. The H1-H2A crosslinks form equally well in whole nuclei, lysed nuclei, and H1-containing mononucleosomes isolated from a sucrose gradient. These results suggest that there exist major H1 interactions within the nucleosome.