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Biomedical subjects

R M Hicks

Publications and source records attributed to R M Hicks.

At least 73 records · Page 4Linked to original sources
PubMed1977

The importance of synergy between weak carcinogens in the induction of bladder cancer in experimental animals and humans.

It is now well established that the interaction of multiple environmental factors may increase the incidence of some human cancers more than exposure to a single carcinogen. With an in vivo experimental rat model, we have demonstrated a synergistic effect in bladder carcinogenesis between a subcarcinogenic dose of the strong bladder carcinogen, N-methyl-N-nitrosourea, and saccharin- or cyclamate-containing diets. If these artificial sweeteners are capable of interacting with other environmental bladder carcinogens, their potential for increasing the incidence of human bladder cancer is greater than many more potent chemical carcinogens, because of their wide distribution as food additives to all sections of the population. Retrospective epidemiology shows no evidence of such risk from saccharin at current levels of consumption. No comparable studies are available for cyclamate, which was consumed in greater quantities but for relatively few years. It is emphasized that it is possible for interaction between multiple factors to contribute to the incidence of human bladder cancer as it does in other human organs and in other animal species.

2-Naphthylamine↗
PubMed1976

Scanning electron microscopy of cell-surface changes in methylnitrosurea (MNU)-treated rat bladders in vivo and in vitro.

Scanning electron microscopy has been used (1) to characterize epithelial cells of bladders from normal rats and from rats treated with a single initiating but non-carcinogenic dose of 2 mg methylnitrosurea (MNU), 24 h and 6 weeks after treatment; and (2) to compare morphological aspects of epithelial differentiation in organ culture of bladder explants taken from untreated and MNU-treated rats at these time intervals. There are marked differences in vivo between the surface organization of normal urothelium and urothelium undergoing reversible hyperplasia following MNU treatment. Maturation of the normal rat bladder epithelium in vivo is shown to be related to a series of well-defined cell-surface changes readily identified by SEM. By contrast the maturation response is perturbed in the hyperplastic epithelium; the cells lose their ability to differentiate normally and form instead an excess of stubby globular microvilli which project from the cell surface. In organ culture, maturation of normal bladder epithelium (both in re-epithelialized areas of the explant and in areas of epithelial outgrowth over cellulose acetate substrates) can be also related to a series of cell surface changes showing close similarities to those in vivo. However, epithelial maturation remains defective in organ cultures of bladders from MNU-treated animals. The closely parallel behaviour of the bladder epithelium in vivo and in vitro in both normal and treated tissues underlines the potential value of the bladder organ culture system for studying the comparative biology of hyperplastic development produced by a single initiating dose of MNU and suggests it will be useful with which to study carcinogenesis following multiple doses of MNU.

Animals↗
PubMed1976

Mucocutaneous lymph node syndrome in the United States.

Sixteen patients with an unusual and distinct symptom complex were encountered during a four-year period. Principal features of this syndrome are (1) fever lasting more than seven days; (2) conjunctival injection; (3) changes in the mouth consisting of erythema of the oropharynx, "strawberry tongue", and erythema of the lips; (4) indurative edema of hands and feet with palm and sole erythema followed by desquamation of the fingertips; and (5) an erythematous rash. Associated features were lymphadenopathy, pyuria, aseptic meningitis, diarrhea, arthritis, and arthralgia. Although usually a self-limited illness, one patient died with massive coronary artery thrombosis on the 19th day of illness. This syndrome appears to be clinically and pathologically similar to mucocutaneous lymph node syndrome, an illness prevalent in Japan but previously unrecognized by American clinicians. Pathologic features suggest a relationship to infantile periarteritis nodosa.

Arthritis, Juvenile↗
PubMed1976

Membrane changes during urothelial hyperplasia and neoplasia.

Normal mammalian urothelium has a complex pattern of morphogenesis and cell differentiation. The luminal face of the polyploid, superficial cells is limited by a morphologically unique plasma membrane with a highly ordered substructure. This membrane is a convenient marker for normal differentiation in the urothelium. In reversible, benign hyperplasia, following cytotoxic damage, the luminal face of the most superficial layer of cells is limited by an undifferentiated membrane which is comparable to the plasma membrane of normal basal cells. When the hyperplasia regresses, normal differentiation of the urothelium is reestablished, and the normal, specialized surface membrane is again produced. In both preneoplastic hyperplasia and early neoplasia induced by various carcinogenic regimens, a novel form of differentiation affecting the surface membrane is seen in some superficial cells. Microvilli form on their free luminal face and are limited by a membrane with an unusual, structured glycocalyx, which is not found in normal urothelium or benign hyperplasia. This glycocalyx also develops on some cells in transitional cell carcinoma of the bladder in man. This novel glycocalyx may be a morphological marker for neoplastic transformation in the urothelium.

Animals↗
PubMed1975

Acute biochemical and morphological effects of N-nitrosomorpholine in comparison to dimethyl- and diethylnitrosamine.

Some biochemical and ultrastructural changes induced in the livers of rats treated with N-nitrosomorpholine are described and compared with parallel observations in rats given dimethyl- or diethylnitrosamine. Hepatotoxic doses of the nitrosamines caused inhibition of incorporation of [14C]leucine into hepatic proteins, accompanied by progressive disaggregation of polysomes which paralleled the known time course of metabolism of each compound. Dimethylnitrosamine (DMN) and N-nitrosomorpholine (NM) inhibited incorporation of [14C]orotate into liver RNA but diethylnitrosamine (DEN) caused a slight stimulation of orotate incorporation. Electron microscopy revealed similar hepatic cytoplasmic changed induced by each nitrosamine, including dilation and degranulation of the rough surfaced endoplasmic reticulum and subsequent increase of the smooth endoplasmic reticulum. Nuclear changes differed with each compound, N-nitrosomorpholine having more marked effects than either dialkyl compound. The results are discussed with particular reference to the metabolism of N-nitrosomorpholine in the liver.

Animals↗
PubMed1975

Evaluation of a new model to detect bladder carcinogens or co-carcinogens; results obtained with saccharin, cyclamate and cyclophosphamide.

A sensitive rat model has been designed to detect potential weak bladder carcinogens or co-carcinogens. The test compound is given to animals which have received a single initiating, but non-carcinogenic, dose of N-methyl-N-nitrosourea (MNU). The model has been used to investigate two compounds currently under suspicion as weak bladder carcinogens, namely sodium saccharin and sodium cyclamate, and one compound known to be cytotoxic but not carcinogenic for the bladder epithelium namely cyclophosphamide. For comparison, these three compounds were also tested as solitary carcinogens in animals not pre-treated with MNU. At the very high dose levels used, sodium saccharin and sodium cyclamate were weak solitary carcinogens producing 4/253 and 3/228 bladder tumours respectively, and the first of these tumours did not appear for more than 80 weeks. When tested in the MNU/rat model more than half the animals receiving either sodium saccharin or sodium cyclamate developed bladder tumours from 10 weeks onwards. By contrast, cyclophosphamide failed to produce any tumours when tested either as a solitary carcinogen or in the MNU/rat model. It must be emphasized that the doses of saccharin and cyclamate used were far higher than those consumed by man, including diabetics, and these results should not be directly extrapolated to man without careful consideration of many other factors including negative epidemiological findings. The theoretical basis of the model is discussed and also the relevance, in terms of environmental human exposure, of detecting compounds which have a synergistic effect with other known bladder carcinogens. It appears that this model can be used to detect a carcinogenic or co-carcinogenic potential in compounds which are organotropic for the bladder more rapidly and with fewer animals than if the compounds are tested as solitary carcinogens by more conventional methods. It is suggested that it could be used to detect those compounds which require further investigation.

Administration, Oral↗
PubMed1974

Morphological and biochemical effects of 1,2-dimethylhydrazine and 1-methylhydrazine in rats and mice.

Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes including nucleolar microsegregation and changes in the endoplasmic reticulum and mitochondria. 1-Methylhydrazine caused little morphological change in the liver. Tumours of the colon and kidney and also massive cystic hyperplasia of the liver were found in some of the rats and tumours of the anal margin and kidney in some of the mice, following single doses of 1,2-dimethylhydrazine. Incorporation of amino acids into rat liver proteins was inhibited by 1,2-dimethylhydrazine, which also caused disaggregation of hepatic polysomes. No effects on hepatic protein synthesis by 1,1-dimethylhydrazine or 1-methylhydrazine were observed. Similarities between the effects of 1,2-dimethylhydrazine, cycasin and dimethylnitrosamine are discussed.

Animals↗