Hormone replacement therapy and breast cancer, endometrial cancer and cardiovascular disease: risks and benefits.

The relatively restricted use of hormone replacement therapy in the United Kingdom has frequently been noted. It is possible that low prescribing rates may, in part, be due to the difficulty in interpreting the wealth of research evidence relating to the risks and benefits of hormone replacement therapy. Conflicting conclusions from research can cause considerable uncertainty and confusion. This paper reviews the evidence relating to hormone replacement therapy and the risks of breast cancer, endometrial cancer and cardiovascular disease and discusses the issues which require critical assessment. This should add to the information base available to general practitioners and thus assist in decision-making in the context of uncertainty.

Maturation-related changes in mass and elemental contents of secretory granules as measured by electron-microprobe.

The relationship between granule density, protein content, and Ca and S contents were studied in two secretory granule fractions, from parotid glands of the rat, previously shown to constitute different stages in granule maturation. The density of the lighter fraction was between 1.133 and 1.142 g/ml, while that of the heavier fraction was greater than 1.142 g/ml. The mean protein content of the denser granules was 12% greater than that of the lighter granules (P less than 0.03), while the dry-mass elemental concentrations in the two granule fractions were unchanged. These results indicate that protein is added to granules during the maturation process (presumably by vesicular traffic), and that the resulting increase in granule density is not driven simply by decrease in water content and/or increased concentrations of inorganic Ca or S in the granules. The elemental concentration values also indicate that the diffusible elements permeate the granule membrane during the fractionation procedures.

Evidence for two conductance/exchange pathways for chloride in rat parotid secretory granules.

Electron probe x-ray microanalysis was used to determine that bromide is localized to rat parotid secretory granules at early stages of an in situ Cl/Br washout experiment. Chloride efflux and bromide influx across the secretory granule membrane occurred with a time order of minutes. Since the Cl washout data indicated minimal Cl binding within the granule, and therefore minimal Br binding, the Br localization results suggest the presence of two or more anion conductance/exchange pathways in the granule membrane for the Cl (Br) ion.

Beam induced mass loss in high resolution biological microanalysis.

Electron beam induced loss of mass from the organic matrix and from higher Z constituents of biological samples was measured by monitoring bremsstrahlung and peak changes in EDS spectra. When any effects of contamination, extraneous X-rays, beam current drift, specimen drift, and specimen shrinkage were monitored and corrected for, the three types of samples gave consistent and similar results at 296 K. Bremsstrahlung losses averaged 45%, 46% and 50% respectively for muscle homogenate, salivary gland sections and albumin. Sulphur losses average 74%, 72% and 86% for the same three sample types. No other elements suffered significant losses. D1/e for bremsstrahlung averaged 0.14 C/cm2. Bremsstrahlung loss at 93 K began approximately one order of magnitude higher in dose, and the extent of loss varied. Sulphur losses, however, were greatly reduced at low temperatures.