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Biomedical subjects

I T Johnson

Publications and source records attributed to I T Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Habitual intake of fruits and vegetables amongst patients at increased risk of colorectal neoplasia.

We assessed consumption of fruit and vegetables amongst patients with ulcerative colitis, colorectal polyps or previous carcinoma. The dietary intakes for 119 patients attending a gastroenterology clinic for colonoscopy were assessed using a questionnaire. A single age- and sex-matched control subject was recruited for each patient. The patients consumed 12.8% less energy than the controls (P < 0.02) and 28.9% less fruit and vegetables (P < 0.0001). Patients with neoplastic disease consumed 21% less fruit and vegetables than the controls (n = 60; P < 0.01). This group of patients at increased risk of colorectal cancer selected diets containing significantly less fruit and vegetables than symptomless controls.

Case-Control Studies↗
PubMed1997

Effect of saponin on the transmucosal passage of beta-lactoglobulin across the proximal small intestine of normal and beta-lactoglobulin-sensitised rats.

The ability of saponins and glycoalkaloids to permeabilise the mammalian intestinal barrier has been previously demonstrated in vitro, leading to the hypothesis that membranolytic saponins may facilitate transfer to the tissues of otherwise excluded macromolecules. An enhanced uptake of, for instance, potentially allergenic species from the lumen is one of the factors that may affect the induction of food allergy, and its presentation in already sensitised individuals. In the experiments described here, an increase in the transmucosal uptake of the milk allergen beta-lactoglobulin (beta LG) was assessed in non-sensitised and sensitised Brown Norway rats in the presence of Gypsophila saponin. Isolated jejunal loops were exposed in vivo to either beta LG followed by saponin, saponin followed by beta LG or the two compounds simultaneously. Portal vein blood samples were collected and assayed for beta LG and rat mucosal mast cell protease (RCMP II) activity. Mucosal tissue was also examined histologically and assayed for histamine content. Sham-operated animals, exposed to physiological buffer alone, were included as controls and beta LG measurements corrected for this component which was negligible. No transfer of beta LG occurred in the absence of saponin in non-sensitised rats, whereas a significant enhancement was observed in the presence of saponin. beta LG was detected in the portal circulation of sensitised rats exposed to beta LG alone; however addition of saponin to the intestinal lumen further enhanced this uptake, possibly by an independent mechanism. Histological examination of the mucosal epithelium exposed to saponin revealed damage, especially at the villus tips. Mucosal histamine and serum RCMP II concentrations were consistent with the differences observed between sensitised and non-sensitised animals. It is concluded that exposure to food constituents capable of permeabilising the mucosal epithelium may increase the risk of sensitisation to dietary antigens.

Animals↗
PubMed1997

Soluble non-starch polysaccharides derived from complex food matrices do not increase average lipid droplet size during gastric lipid emulsification in rats.

The creation of a finely dispersed lipid emulsion is essential for efficient hydrolysis of dietary triglycerides. The effectiveness of emulsification within the stomach depends upon the shear force generated by gastric motility and the concentration of emulsifiers present in the gastric contents. Other dietary constituents can modify these factors, and previous studies have suggested that the presence of soluble non-starch polysaccharides (NSP) during digestion might increase the average size of intraluminal emulsion droplets. In the present study, we developed a new technique for the isolation and analysis of intraluminal lipid emulsions by optical diffraction analysis. The method was applied to rats fed powdered semipurified diets that were free of all NSP or supplemented with insoluble cellulose, guar gum, or NSP derived from apple, carrot or rolled oats. Cellulose had no significant effect on emulsion size, and there was no evidence that the average sizes of lipid droplets in the gastric fundus or antrum were higher than control values in rats fed diets supplemented with any source of soluble NSP. In the groups fed oats and cooked carrot NSP, the mean droplet diameters approached half the values for diets free of NSP or containing insoluble cellulose. The difference between rats fed NSP from cooked carrot and those fed cellulose was significant in the proximal stomach (P < 0.05), and that between rats fed raw oats and rats fed cellulose was significant in the distal stomach (P < 0.05). Soluble dietary fiber does not inhibit lipid or cholesterol absorption via any inhibition of lipid emulsification.

Absorption↗
PubMed1997

Plant anticarcinogens.

There is strong epidemiological evidence to suggest that the consumption of diets rich in plant materials is associated with a reduced risk of cancer. Human beings are probably adapted to consume relatively large quantities of biologically active phytochemicals derived from as many as 300 different plant genera. Plant foods contain a variety of potentially anticarcinogenic secondary metabolites, and these can conveniently be classified as blocking agents and suppressing agents. Blocking agents modulate the activation and detoxification of carcinogens, whereas suppressing agents are thought to modify post-initiation events including cellular differentiation, proliferation and apoptosis. The full significance of these mechanisms needs to be assessed in further research, preferably using suitable biomarkers in human subjects.

Anticarcinogenic Agents↗
PubMed1996

Brown Norway rat model of food allergy: effect of plant components on the development of oral sensitization.

The Brown Norway (BN) rat was examined as a model for investigating factors that influence the development of food allergy. An antigen dose-response curve for the production of antigen-specific reaginic antibody (IgE) induced through the oral route was determined. Animals were dosed orally with 1.0, 2.5, 5.0, 7.5, 10.0 and 12.0 mg ovalbumin/ml (0.5 ml/100 g twice a week for 6 wk). To promote IgE production the adjuvant carrageenan was administered once a week by the i.p. route. The effect on oral sensitization of 1.5 mg Gypsophila sp. saponin/ml administered together with the antigen on oral sensitization was examined in animals treated with 2.5, 6.0 or 10.0 mg ovalbumin/ml. The number of animals producing antigen specific reaginic antibody in response to 2.5 mg ovalbumin/ml was significantly increased (P < 0.01) in the group that received saponin with 2.5 mg ovalbumin/ml. These studies indicate that the BN rat is a sensitive model for the investigation of allergic reactions to food and has the potential to determine the impact of other dietary factors on the development of oral sensitization.

Adjuvants, Immunologic↗
PubMed1996

Fermentable carbohydrate modulates postprandial enteroglucagon and gastrin release in rats.

We studied the effects of a fermentable sugar-alcohol (lactitol) on the concentrations of enteroglucagon and gastrin in the blood of rats for 7.5 h after feeding. The control and treatment groups were fed on semi-purified diets containing either non-fermentable cellulose or lactitol respectively, at 100 g/kg. Compared with the cellulose-fed group, the animals fed with lactitol had higher levels of enteroglucagon (5-10 times higher than control; P < 0.05) and lower serum gastrin (70-80% of control; P < 0.05) for several hours after the withdrawal of feed. In contrast, varying the level of dietary lipid (maize oil) over a range of 8-120 g/kg had no effect on the release of either peptide. These results suggest that poorly absorbed fermentable dietary carbohydrate stimulates postprandial plasma enteroglucagon and inhibits serum gastrin release in the rat. The mechanism is uncertain but an endocrine response by the colon to fermentation products seems probable.

Animals↗
PubMed1996

Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes.

To test the hypothesis that fish oil supplementation can inhibit the expression of functionally associated molecules on the surface of human blood monocytes, we randomly assigned 12 healthy adults to receive either an n-3 polyunsaturated fatty acid-rich fish oil supplement for 21 d or to receive no supplement. The percentage of monocytes expressing major histocompatibility complex (MHC) class II molecules (HLA-DR, -DP, and -DQ), intercellular adhesion molecule-1, and leukocyte-function-associated antigen-1, and the intensity of expression of each molecule were quantified before and after the study period. Monocytes were examined immediately after blood sampling and again after incubation in serum-free culture medium for 24 h in the presence of interferon-gamma to up-regulate expression of MHC class II molecules by the monocytes. The intensity of expression of all the monocyte surface molecules examined was significantly reduced after fish oil supplementation (P < 0.025), although there was no change in the percentage of monocytes expressing each molecule. After incubation with interferon-gamma, there was a similar inhibition of surface molecule expression (with the exception of HLA-DQ) by monocytes from the fish oil-supplemented group, and there was a reduction in the percentage of monocytes expressing both HLA-DR and -DP molecules (P < 0.025). No significant changes were observed in the reference group. Dietary supplementation with fish oil can inhibit the expression of surface molecules involved in the function of human antigen-presenting cells, a potential mechanism by which n-3 fatty acids may suppress cell-mediated immune responses.

Adult↗
PubMed1996

Fermentable carbohydrates elevate plasma enteroglucagon but high viscosity is also necessary to stimulate small bowel mucosal cell proliferation in rats.

Enteroglucagon is a collective term for a small family of peptides derived from proglucagon by post-translational processing in the L-cells of the distal small intestine and colon. There is evidence that it inhibits gastric secretion, and high levels of enteroglucagon occur in plasma during intestinal adaptation, which suggests that it may also function as a trophic factor for the intestine. Certain types of soluble non-starch polysaccharide (dietary fiber) stimulate the release of enteroglucagon in rats but the mechanism is unknown. In this study we explored the importance of the viscosity and fermentability of nonabsorbed carbohydrates as determinants of plasma enteroglucagon and mucosal cell proliferation in the distal ileum of rats. Replacement of cellulose (10 g/kg) with guar gum in a semisynthetic diet led to a prompt and sustained rise in plasma enteroglucagon concentrations. Our initial hypothesis that this was a consequence of delayed nutrient absorption was disproven by the fact that hydroxypropylmethylcellulose (HPMC), a viscous but nonfermentable polysaccharide, had no effect on plasma enteroglucagon under the same conditions. In contrast, the nondigestible disaccharide lactitol led to a prolonged rise in plasma enteroglucagon, similar to that observed with guar gum. Lactitol is nonviscous, but highly fermentable, and we conclude that fermentable carbohydrate is an important stimulus for the release of enteroglucagon under our experimental conditions. There was no evidence that enteroglucagon released by this mechanism exerted trophic effects on the distal small intestinal mucosa.

Animals↗
PubMed1995

The effects of and interactions between fermentable dietary fiber and lipid in germfree and conventional mice.

BACKGROUND/AIMS: Dietary fiber can stimulate intestinal epithelial cell proliferation. The aim of this study was to resolve the different roles of fermentation and intraluminal viscosity on this trophic action and to investigate reported interactions between fiber and dietary fat. METHODS: Conventional and germfree mice were fed guar gum in combination with low- or high-lipid diets for 2 weeks, and crypt cell production rates were determined. RESULTS: Guar gum significantly stimulated proliferation in the small intestine, especially when combined with fat. Lipid itself also stimulated proliferation in the small intestine and had a direct trophic effect in the cecum and colon of the germfree mice. Fiber markedly stimulated proliferation in the cecum and colon but only in the conventional group. Interactions between lipid and bacteria and between guar gum and bacteria were also observed in the small intestine. CONCLUSIONS: Guar gum has a trophic effect in the small bowel, probably related to viscosity, in addition to its fermentation-related actions in the colon. Positive interaction with lipid may be associated with delayed absorption. Lipid also has its own direct actions on small bowel mucosal proliferation, which are attenuated by the presence of bacteria.

Animals↗
PubMed1995

On the cytotoxicity and genotoxicity of allyl and phenethyl isothiocyanates and their parent glucosinolates sinigrin and gluconasturtiin.

Four compounds commonly found in the human diet, allyl isothiocyanate (AITC), phenethyl isothiocyanate (PEITC) and their parent glucosinolates sinigrin and gluconasturtiin, were tested for cytotoxic and genotoxic effects in a Chinese hamster ovary cell line (CHO). The isothiocyanates were found to be more than one thousand times more cytotoxic than the glucosinolates, showing significant cytotoxic activity at concentrations below 1.0 microgram/ml. AITC was unable to induce either chromosome aberrations or sister chromatid exchanges (SCEs) even at highly cytotoxic doses. In contrast, PEITC was found to induce both aberrations and SCE at concentrations of 0.9-1.2 micrograms/ml whilst sinigrin and gluconasturtiin induced aberrations at concentrations above 2 mg/ml.

Animals↗
PubMed1995

Cytotoxic and clastogenic effects of benzyl isothiocyanate towards cultured mammalian cells.

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables present in the human diet, has previously been shown to induce chromosome aberrations in an Indian muntjac cell line. The results of this study show that it also induces both chromosome aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells in the absence of an exogenous metabolic activation system and induces DNA strand breaks as measured by the single-cell gel electrophoresis assay. However, whereas it increased the number of aberrations four-fold, it was not able to raise SCE levels by more than 50% and there was a levelling-off in the dose-response curve. Whereas the survival curve of CHO cells exposed to BITC was linear in shape, that of the human colorectal adenocarcinoma cell line HT29 was found to fit the exponential model (with an alpha equivalent of 0.28 and a beta equivalent of 2.80, where the concentration of BITC is measured in micrograms/ml). This pattern of clastogenic and cytotoxic activities is reminiscent of that generated by ionizing radiation and certain radiomimetic chemotherapeutic agents.

Adenocarcinoma↗
PubMed1995

Selective toxicity of compounds naturally present in food toward the transformed phenotype of human colorectal cell line HT29.

It has previously been observed that allyl isothiocyanate, a compound naturally present in the diet, is more cytotoxic toward the human colorectal adenocarcinoma cell line HT29 in its control transformed state than after exposure to sodium butyrate or to dimethylformamide, which slow growth and induce differentiation (detransformation). In the present study, a range of other dietary compounds were assayed for such selective toxicity. These compounds were chosen as constituents of foodstuffs that have been identified from epidemiologic studies as being potentially antitumorigenic and also as having anticarcinogenic activity in experimental models. Benzyl and phenethyl isothiocyanate, benzyl thiocyanate, and quercetin showed decreased toxicity towards HT29 after detransformation of the cells by one or both treatments, whereas no change was observed in the sensitivity to diallyl sulfide or diallyl disulfide. It is proposed that the presence of such selectively toxic compounds in the diet may inhibit the development of tumors by interfering with the growth of preneoplastic lesions while having little effect on normal cells. The cumulative effects of these inhibitions may contribute to the chemopreventive properties of the parent foodstuffs observed in epidemiologic studies.

Adenocarcinoma↗
PubMed1995

Egg consumption and risk-markers for colorectal neoplasia.

A strong positive relationship between dietary intake of eggs and risk of colorectal cancer has been observed in a number of epidemiological surveys. In this study we investigated the relationship between egg consumption and intermediate biomarkers of crypt cell proliferation in the colon and rectum of 75 patients who had adenomatous polyps or no evidence of bowel disease. Biopsies of normal flat mucosa were obtained at colonoscopy, and microdissected crypts were used to measure crypt length, frequency of mitosis per crypt and spatial distribution of mitoses within the crypt. There was no significant difference in the consumption of eggs by patients with adenomatous polyps (n = 53) and those without (n = 22). There was no significant positive correlation between frequency of egg consumption and any of the parameters of crypt cell proliferation in the group as a whole, nor when the patients with polyps were analysed separately. This study provides no biological evidence of any relationship between egg consumption and abnormal cell proliferation among patients at relatively high risk of colorectal neoplasia.

Abdominal Pain↗