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R M Hicks

Publications and source records attributed to R M Hicks.

At least 19 recordsLinked to original sources
PubMed1992

Comparative teratogenicity of nine retinoids in the rat.

he comparative teratogenicity of nine retinoids in Wistar rats was investigated. The compounds studied and dose levels tested (mg/kg) were: all-trans-retinoic acid (TRA), 6.25, 12.5, 25, 50, 100; etretinate (ETR), 25, 50; acitretin (ACIT), 25, 50; 13-cis-retinoic acid (13CRA), 100, 200; and five retinamides, each at 300 and 600 mg/kg, N-(4-hydroxyphenyl)-retinamide (4HPR); N-tetrazol-5-ylretinamide (TZR); N-butylretinamide (NBR); N-ethylretinamide (NER); 13-cis-N-ethylretinamide (13CNER). Retinoids were administered by oral intubation on days 10 and 11 post coitum (p.c.). Dams were killed on day 22 p.c. and examinations carried out to assess teratogenic potential. TRA, ETR, ACIT, 13CRA and 4HPR increased the incidence of resorptions. The incidence of abnormal fetuses, irrespective of the specific abnormalities induced, was markedly increased (50-100%) by TRA, ETR, ACIT, 13CRA and 4HPR, whereas TZR and NBR caused moderate increases (20-50%), and NER and 13CNER induced mild increases (10-20%). The incidences of CNS, craniofacial and urinogenital defects were generally high with TRA, ETR, ACIT and 13CRA. Cardiac vessel defects were markedly increased by 4HPR. Using a number of criteria, a generalized ranking order of the toxicity of the compounds was drawn up: TRA > ETR > ACIT > 13CRA > 4HPR > TZR identical to NBR > NER identical to 13CNER. The ranked order of relative in-vivo teratogenicity for the nine retinoids is compared with a previously reported in-vitro assessment of the compounds using a rat whole embryo culture technique.

Abnormalities, Drug-Induced↗
PubMed1986

Induction of morphological changes in the urothelium of cultured adult rat bladder by sodium saccharin and sodium cyclamate.

The direct effects of sodium saccharin and sodium cyclamate on the morphology of organ cultures of normal rat bladder have been studied by histology and scanning electron microscopy (SEM). Untreated cultures retained histologically normal urothelia up to 89 days with cell surface features characteristic of mature, fully differentiated superficial cells and maturing intermediate cells. Continuous treatment with either sodium saccharin (6 or 12 mM) or sodium cyclamate (12 or 24 mM) induced progressive abnormalities in the cultured urothelium. Acute toxicity was not seen but focal necrosis was observed with the higher dose of each compound and histological abnormalities were more severe with the higher doses. Sodium saccharin induced mild hyperplasia of the urothelium on the surface of the culture and foci of altered epithelial polarity from 14 days; abnormal nuclear staining plus changes in the basal lamina were evident from 28 days and were pronounced from 56 days onwards. Hyperplasia of the urothelium over the explants was mild but there were extensive epithelial outgrowths onto the culture support. In general, sodium cyclamate induced more severe changes than did sodium saccharin, with alterations in epithelial cell polarity plus basal cell changes from 14 days and focal nodular urothelial hyperplasia over the explant and gross hyperplasia between the explant and culture support and in the outgrowth from 28 days. The severe and rapid surface changes, evident by SEM, were similar both in saccharin-treated and in cyclamate-treated cultures. There was some early loss of superficial cells to reveal underlying immature cells which, together with the remaining mature cells, developed abnormal blebs and processes. From 14 days small immature cells were located at the culture surface between the mature cells. These were covered by a variety of membrane protrusions including long pleomorphic microvilli. Sodium cyclamate-treated cultures mostly had fewer small membrane protrusions than sodium saccharin-treated cultures but more pleomorphic microvilli. These morphological changes induced in the rat urothelium in vitro by direct treatment with sodium saccharin and sodium cyclamate are thus similar to those described previously in association with in vivo long-term feeding studies of sodium saccharin to rats and with both in vivo and in vitro treatment of the rat urothelium with the bladder carcinogen N-methyl-N-nitrosourea (MNU).

Animals↗
PubMed1979

The isolation and analysis of the luminal plasma membrane of calf urinary bladder epithelium.

The luminal plasma membrane of calf urinary bladder epithelium (urothelium) has been isolated by a method designed to preserve enzymic activity as well as structural integrity. The yield was about 80 micrograms per calf bladder. Low levels of 5' nucleotidase, Mg2+-ATPase and (Na+ + K+)-ATPase activities were found in the luminal membrane fraction. Cerebroside was the major lipid present and dodecyl sulphate gel electrophoresis revealed a complex protein and glycoprotein composition in the whole membrane. A membrane fraction consisting of only the plaque areas was shown to have a simpler protein composition with major polypeptides of apparent Mr 12 000 and 22 000. These may associate to form a 30 000 apparent Mr complex which could represent the individual 'particles' of the dodecameric subunits seen by electron microscopy in the plaque regions.

Animals↗
PubMed1979

Response of the rat to saccharin with particular reference to the urinary bladder.

Male and female Wistar rats were administered sodium saccharin for life (2 yr) either in the drinking water or diet. The maximum palatable dose of saccharin in the drinking water was found to be 2 g/kg/day and, even then, there was some voluntary restriction of fluid intake in the males. By contrast, double this dose--namely 4 g/kg/day, was palatable in the diet. A control group of rats of both sexes received saccharin-free diet and drinking water. Mild urothelial hyperplasias developed from 85 weeks in rats of both sexes receiving saccharin either in the drinking water or diet; the incidence was statistically significant in both the bladders and kidneys of rats receiving the higher dose of saccharin in the diet, but in the kidneys only of rats receiving the lower dose of saccharin in the drinking water. Telangiectasia of the vasa recta was significant in saccharin-treated rats of both sexes at both doses. A very low incidence of bladder tumours, exclusively in males receiving the higher saccharin dose in the diet was seen from 95 weeks. No consistent relationship between bladder epithelial hyperplasias and crystalluria could be demonstrated, although all 3 bladder tumours were associated with some form of mineralisation. Results suggest a particular susceptibility of males to saccharin treatment. The possibility that saccharin may promote, or enhance, the development of latent tumour cells already present in the experimental population, rather than initiate carcinogenesis per se is considered.

Animals↗
PubMed1977

The surface structure of the tegument of Schistosoma haematobium.

The surface structure of the tegument of adult S. haematobium (Egyptian strain) was studied by scanning electron microscopy. Most of the dorsal surface of the male is studded by prominent, spine-covered tubercles, or bosses, not found in the female. Structural details of the oral and ventral suckers and sensory organelles, and local variations in the tegument are described.

Animals↗
PubMed1977

Detection of neoplastic and preneoplastic urothelia by combined scanning and transmission electron microscopy of urinary surface of human and rat bladders.

Scanning and transmission electron microscopy reveal distinct differences between the appearance of the luminal surface membrane of normal urothelium and those of transitional cell tumours of both human and rat bladder. The luminal surface membrane of the preneoplastic rat urothelium shows features similar to those seen in the fully developed tumour. In human tumour-bearing bladders the urothelium away from the transitional cell tumour is not recognizable as being preneoplastic by light microscopy. However, by scanning or transmission electron microscopy, the luminal membrane in some areas shows changes identical to those in the preneoplastic rat bladder. These observations are in accordance with the clinical behaviour of the urothelium in patients with vesical transitional cell tumours which tend to recur in disparate site. We suggest that scanning electron microscopy of the bladder urothelium away from the tumour may be of prognostic value for indicating the subsequent biological behaviour of the urothelium.

Animals↗
PubMed1977

Frozen-surface replicas of rat bladder luminal membrane.

A method for preparing replicas of the luminal surface of frozen, unfractured but deep-etched whole bladder tissue using a Bullivant type II device is described. A small piece of glutaraldehyde-fixed (uncryoprotected) rat bladder is rinsed in distilled water, mounted luminal side uppermost on a specimen holder and rapidly frozen by immersion in liquid nitrogen (cooled below its boiling point in a vacuum) or by contact with a copper block at liquid nitrogen temperature. The specimen is processed in the type II device without fracturing and 'deep-etched' by allowing a longer period than usual to elapse before shadowing. The results are assessed with reference to the appearance of the luminal membrane in standard freeze-fracture replicas, and some preliminary observations on the structure of the normal luminal membrane and its counterpart in bladder tumours are presented.

Animals↗
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↗