SUMMARY Ageing changes in the normal human female breast were studied to determine their significance for the evolution of mammary cancer. Employing the morphometric techniques of point counting and planimetry, objective quantitative measurements were made of the structure of the normal female breast in 58 subjects from the prepubertal to late postreproductive period. The relative amounts of epithelial and connective tissue varied with age, and the epithelial elements (combined lobular and extralobular) were unevenly distributed within the gland, with lower containing more than upper quadrants. The upper outer quadrant, however, usually contained the largest proportion of lobular units, which may relate to the higher incidence of lobular carcinoma found in this quadrant. Involution was shown to be a premenopausal rather than postmenopausal phenomenon. Mammary dysplastic changes were uncommon in all age groups.Normal human breast morphology has been well documented at both light and electron microscopical levels.'-8 Similar studies have also been conducted in breasts containing clinical carcinomas in order to determine early malignant and premalignant changes.9-l" The extent to which normal ageing processes contribute to these changes is uncertain, however, since these are poorly documented. The present study was undertaken to establish on a quantitative basis the normal sequence of morphological changes that take place in the non-neoplastic female breast from the prereproductive to postreproductive periods. Particular attention was devoted to determining features that might have relevance for the subsequent evolution of breast cancer. Material and methods BREAST SAMPLESSubcutaneously removed mammary glands, excluding the nipple and axillary tail, were routinely collected from female subjects at necropsy. The breasts were fixed in buffered formalin for three to seven days depending on size and fat content. In all, 58 breasts were processed covering the seven decades from 10 to 80 years, and each group contained at Accepted for publication 8 November 1984 least eight samples. No bilateral specimens were taken. PREPARATION FOR SUBGROSS ANALYSISAfter fixation, breasts were sliced coronally (2 mm slices) on an Excel Boston slicing machine and labelled on their superior and lateral extremities to aid orientation. Where necessary, fixation was continued for a further 24 h. Whole slices were stained with Harris's haematoxylin, dehydrated in graded ethanol (70%, 95%, and 100%), and cleared and stored in methyl salicylate.'2 PREPARATION FOR LIGHT MICROSCOPY After qualitative and quantitative examination at the subgross level tissue blocks were removed for histology. Twenty blocks (five from each quadrant), each measuring 1-5 x 1-5 x 0-2 cm, were selected at random from five alternate slices. Before processing for light microscopy blocks were washed in several changes of absolute alcohol over a period of three days to remove all traces of methyl salicylate. After processing for routine histology 8 ,um sections were stai...

Muscle extracts were subjected to fractionation with ethanol, chromatography on DEAE-cellulose, precipitation with (NH4)2SO4 and gel filtration on Sephadex G-200. These fractions were assayed for protein phosphatase activities by using the following seven phosphoprotein substrates: phosphorylase a, glycogen synthase b1, glycogen synthase b2, phosphorylase kinase (phosphorylated in either the alpha-subunit or the beta-subunit), histone H1 and histone H2B. Three protein phosphatases with distinctive specificities were resolved by the final gel-filtration step and were termed I, II and III. Protein phosphatase-I, apparent mol.wt. 300000, was an active histone phosphatase, but it accounted for only 10-15% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities and 2-3% of the phosphorylase kinase phosphatase and phosphorylase phosphatase activity recovered from the Sephadex G-200 column. Protein phosphatase-II, apparent mol.wt. 170000, possessed histone phosphatase activity similar to that of protein phosphatase-I. It possessed more than 95% of the activity towards the alpha-subunit of phosphorylase kinase that was recovered from Sephadex G-200. It accounted for 10-15% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activity, but less than 5% of the activity against the beta-subunit of phosphorylase kinase and 1-2% of the phosphorylase phosphatase activity recovered from Sephadex G-200. Protein phosphatase-III was the most active histone phosphatase. It possessed 95% of the phosphorylase phosphatase and beta-phosphorylase kinase phosphatase activities, and 75% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities recovered from Sephadex G-200. It accounted for less than 5% of the alpha-phosphorylase kinase phosphatase activity. Protein phosphatase-III was sometimes eluted from Sephadex-G-200 as a species of apparent mol.wt. 75000(termed IIIA), sometimes as a species of mol.wt. 46000(termed IIIB) and sometimes as a mixture of both components. The substrate specificities of protein phosphatases-IIA and -IIB were identical. These findings, taken with the observation that phosphorylase phosphatase, beta-phosphorylase kinase phosphatase, glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities co-purified up to the Sephadex G-200 step, suggest that a single protein phosphatase (protein phosphatase-III) catalyses each of the dephosphorylation reactions that inhibit glycogenolysis or stimulate glycogen synthesis. This contention is further supported by results presented in the following paper [Cohen, P., Nimmo, G.A. & Antoniw, J.F. (1977) Biochem. J. 1628 435-444] which describes a heat-stable protein that is a specific inhibitor of protein phosphatase-III.

An animal model was established to study the toxic effects of hyperoxia and the consequent changes in intracellular antioxidant status. Superoxide dismutase, catalase and glutathione peroxidase activities were measured in erythrocytes, liver and lung, in addition to cellular glutathione concentrations and its associated metabolism. Overt cellular damage was assessed biochemically by measurement of lipid peroxidation, hydrogen peroxide-induced haemolysis and osmotic fragility. Pathological changes were assessed by light and electron microscopy. Up to 11 days exposure of rats to 80% oxygen was not lethal, but resulted in overt cellular damage to red blood cells (haemoglobin concentration decreased from 13.8 +/- 1.4 (SD) g dl-1 to 12.4 +/- 0.5 g dl-1; hydrogen peroxide-induced haemolysis increased from 7.7 +/- 1.6% to 75.1 +/- 13.5% after 11 days of hyperoxia) and to cells of lung (4-fold increase in lipid peroxidation) as well as a biochemical adaptation to the increased concentration of oxygen metabolites (superoxide dismutase increased 3-fold, catalase 5-fold and glutathione peroxidase 2-fold). It is suggested that red cell hydrogen peroxide-induced haemolysis and reduced glutathione concentration may be useful indicators of oxidant stress in the clinical situation.

This case report describes a young man with a 47, XYY karyotype who was convicted of arson. He suffered from a cardiac disorder which may well have been part of the XYY syndrome rather than a chance association. His abnormal karyotype was disclosed in court and used by the defence in a plea in mitigation.

Summary A patient with co‐existent carcinoma and tuberculosis of the Fallopian tube is described. Tuberculosis was diagnosed by the finding of numerous typical granulomata throughout the uterus, tubes and ovaries, and by exclusion of other possible causes of these; and carcinoma by the finding of solid tumour, with a marked anisocytic appearance, invading submucosa. Despite the well recognised epithelial hyperplasia seen in tuberculous salpingitis, there remains no evidence that the occurrence of carcinoma in such cases is other than fortuitous.