Heterocyclic amines: evaluation of their role in diet associated human cancer

1 Heterocyclic amines are formed in parts per billion levels when meat is cooked.
2 The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food.
3 We have shown that MeIQx and PhIP, both in vitro and in vivo , are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines.
4 MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt , we have shown that PhIP induces a characteristic mutational 'fingerprint'.
5 MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.     

A Predominantly Adrenaline-secreting Phaeochromocytoma

A 61-year-old woman who presented with diabetes, nausea, weightloss and sweating was found to have a phaeochromocytoma secretingadrenaline, with a small amount of N-methyIadrenaline. Therewas no significant increase in noradrenaline secretion. Shewas normotensive, and developed profound hypotension in responseto the -adrenergic antagonist phenoxybenzamine. These featuresare unusual in phaeochromocytoma, but similar features occurredin the very few previous reported cases of pure adrenaline-secretingphaeochromocytoma. We conclude that it is important to identifysuch patients, so that they should not be given -adrenergicantagonist drugs.     

Review of 59 patients with hypergonadotrophic amenorrhoea

Summary. Fifty-nine patients presented with elevated concentrations of gonadotrophins and secondary amenorrhoea before the age of 35 years. Fifty-three underwent laparoscopic examination and primordial follicles were observed in 16. Two others had follicles as they later became pregnant and a third showed biochemical evidence of spontaneous ovulation. There were streak ovaries in 12, two with follicles and three others with chromosomal abnormalities, two being 47XXX and one XO/XX. Two other patients had only one ovary each but no follicles. Chromosomal abnormalities were detected in two further patients one being XO/XX and the other a recombinant. Six patients became pregnant, two of them twice, resulting in four term deliveries and four spontaneous abortions. Three other patients showed biochemical evidence of ovulation; one spontaneously, one after oestrogen therapy and the third after treatment with gonadotrophin releasing hormone analogue.     

Modulation of the allergic reactivity of slum children by helminthic infection

Infection by helminthic parasites can cause the polyclonal stimulation of IgE synthesis, possibly via an enhanced production of interleukin-4 (IL-4), and this has been suggested to influence the allergic reactivity of tropical populations where these parasites are endemic. We evaluated a group of urban slum children in Caracas, Venezuela, with a high prevalence of helminthic infection (70.8%), to establish the relationship between the elevated IgE levels (3696 IU/ml) induced by these parasites and various aspects of the allergic response. Although the absolute levels of IL-4 detected in the sera of these children were low (0.65 ± 0.20 ng/ml), a strong positive correlation (r = 0.78) was found between these and serum IgE. The cutaneous immediate hypersensitivity reactivity to extracts of common environmental allergens was relatively low (17.5% to house dust), although that to Ascaris extract was moderately high (49.4%). Significant inverse correlations were found between total IgE levels and the different skin test reaction diameters, including Ascaris. The positivity of Prausnitz-Kustner passive transfer tests was low in this group (34%), with a strong inverse correlation (r= -0.75) being found between this and total IgE levels. Significant inverse correlations were also found between total IgE levels and specific IgE antibody to environmental allergens, and to Ascaris antigen. We suggest that the polyclonal production of IgE stimulated by helminthic infection can suppress the allergic response to environmental and parasite allergens via both mast cell saturation and inhibition of specific IgE production.