Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset and progression of many pathological states. The mechanisms underlying this response are well described in such conditions as wound healing and malignant tumors, where tissue-specific signals enhance the extravasation of blood monocytes and their subsequent differentiation into macrophages. Recent evidence suggests that macrophages may also be stimulated by microenvironmental factors present in diseased tissues to perform distinct, tissue-specific activities. One such factor, hypoxia (low oxygen tension), results from insufficient vascular perfusion of a given tissue. Various studies have shown that experimental hypoxia alters the morphology, expression of cell surface markers, viability, phagocytosis, metabolic activity, and release of cytokines by macrophages. Here we review the evidence for these macrophage responses to hypoxia, the involvement of co-stimuli, and their implications for the role of macrophages in various disease processes. Because the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discuss their possible involvement in the effects of hypoxia on gene expression in macrophages.

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The growth of a tumour in a rigid walled cylindrical duct is examined in order to model the initial stages of tumour cell expansion in ductal carcinoma in situ (DCIS) of the breast. A nutrient-limited growth model is formulated, in which cell movement is described by a Stokes flow constitutive relation. The effects on the shape of the tumour boundary of the material properties (i.e. the viscosity) and the extent to which the cells adhere to the duct wall are studied using numerical and asymptotic methods. It is shown how stable, non-planar, interface configurations result and that, during these initial stages, before the duct wall has been breached, few cells die and a nutrient-rich model is usually sufficient to capture the behaviour. Finally, we discuss the relevance of this approach to DCIS and suggest possible avenues for further work.

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Microscopic studies have been performed on skin biopsies from five patients with occupational argyria. Small brown-black granules were present in the dermis on light microscopy and were intensely refractile with dark-field illumination. Electron microscopy showed that the granules were electron-dense, round or oval in shape and varied in size from 30 nm to 100 nm. They were most numerous in relation to the basal lamina of the eccrine sweat glands, but were also present in relation to the basal lamina of the epidermis and dermal elastic fibres. X-ray microanalysis confirmed that many of the granules contained silver and sulphur. However, selenium, mercury, titanium and iron were also identified and it is probable that these elements were deposited in the skin also as a result of occupational exposure.