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Biomedical subjects

P J Harris

Publications and source records attributed to P J Harris.

At least 19 recordsLinked to original sources

Effect of drought stress on the yield and composition of volatile oils of drought-tolerant and non-drought-tolerant clones of Tagetes minuta.

A drought-tolerant clone of Tagetes minuta L. (Asteraceae) was selected in vitro on a medium containing 60 mM mannitol. In the greenhouse, a decrease in soil field capacity (FC) from 100 to 40 % reduced oil yield by 49, 71 and 71 % for drought-tolerant, non-drought tolerant cloned and seed-grown plants, respectively. In soil at 40 % FC, the drought-tolerant clone had the highest leaf dry weight and oil yield. At 100 % FC, there was no significant difference in leaf dry weight, but the drought-tolerant clone had a significantly higher percentage oil content and yield than seed-grown plants. The main components of the oil were monoterpenes of which trans- and cis-tagetone together were 52.3 % - 64.2 %. Drought significantly altered the content of some oil components.

Acclimatization↗

Experimental determination of the diffusion coefficient in two-dimensions in ferrous sulphate gels using the finite element method.

A novel two-dimensional finite element method for modelling the diffusion which occurs in Fricke or ferrous sulphate type radiation dosimetry gels is presented. In most of the previous work, the diffusion coefficient has been estimated using simple one-dimensional models. This work presents a two-dimensional model which enables the diffusion coefficient to be determined in a much wider range of experimental situations. The model includes the provision for the determination of a drift parameter. To demonstrate the technique comparative diffusion measurements between ferrous sulphate radiation dosimetry gels, with and without xylenol orange chelating agent and carbohydrate additives have been undertaken. Diffusion coefficients of 9.7 +/- 0.4, 13.3 +/- 0.6 and 9.5 +/- 0.8 10(-3) cm2h-1 were determined for ferrous sulphate radiation dosimetry gels with and without xylenol orange and with xylenol orange and sucrose additives respectively.

Chelating Agents↗

Ferulic acid is esterified to glucuronoarabinoxylans in pineapple cell walls.

The ester-linkage of ferulic acid (mainly E) to polysaccharides in primary cell walls of pineapple fruit (Ananas comosus) (Bromeliaceae) was investigated by treating a cell-wall preparation with 'Driselase' which contains a mixture of endo- and exo-glycanases, but no hydroxycinnamoyl esterase activity. The most abundant feruloyl oligosaccharide released was O-[5-O-(E-feruloyl)-alpha-L-arabinofuranosyl](1-->3)-O-beta-D-xylopyranosyl-(1-->4)-D-xylopyranose (FAXX). This indicated that the ferulic acid is ester-linked to glucuronoarabinoxylans in the same way as in the primary walls of grasses and cereals (Poaceae). Glucuronoarabinoxylans are the major non-cellulosic polysaccharides in the pineapple cell walls.

Carbohydrate Sequence↗

Changing concepts of dietary fiber: implications for carcinogenesis.

The dietary fiber (DF) hypothesis suggested that DF, as plant cell walls, protected against colorectal cancer. The implicit assumption in much historic literature was that the readily analyzed and quantified nonstarch polysaccharide (NSP) component was critical in cancer protection. However, the presence of polymeric phenolic components such as lignin or suberin has profound effects on the physicochemical properties of the cell walls and largely determines their physiological properties in humans. In certain groups of food plants, degradation of cell walls that contain neither lignin nor suberin releases ferulic acid and other hydroxycinnamic acids. These acids have antioxidant, antimutagenic, and other anticancer effects, including modulation of gene expression and immune response. Reexamination of literature on cancer protection suggests that plant cell walls containing significant amounts of phenolic components may be the most likely to protect against cancer. In the last 30 years, the definition of DF has been incrementally expanded to incorporate NSP extracted from plant cell walls and from sources other than plant cell walls, then resistant starch, and most recently nondigestible oligosaccharides. On the early definitions, increased consumption of DF could only be achieved by increasing the intake of whole grains, brans, or other food plant material that would increase the intake of plant cell walls containing significant amounts of phenolic components. However, the new definitions make it possible to increase "dietary fiber" without consuming any such materials. We suggest that this could have negative connotations for cancer risk in human populations.

Animals↗

Increased proximal tubule NHE-3 and H+-ATPase activities in spontaneously hypertensive rats.

OBJECTIVE: To investigate renal proximal tubular sodium-hydrogen exchanger 3 (NHE-3) and H+-ATPase activities in young (5-week-old) spontaneously hypertensive rats (SHR) and normotensive Donryu (DRY) rats, in the period during which high blood pressure is developing. METHODS: Five-week-old SHR and DRY rats were weighed and systolic blood pressure recorded. Proximal tubule cells were isolated, loaded with the intracellular pH dye, 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein-acetoxymethyl-ester and acidified with a NH4+/NH3 prepulse. Na+-independent intracellular pH recovery rate (H+-ATPase activity) and initial Na+-dependent intracellular pH recovery rate (NHE-3 activity) were assessed. NHE-3 activity was assessed during inhibition of H+-ATPase with Bafilomycin A1 and during inhibition of any possible NHE-1 activity with Hoe 694. RESULTS: Mean body weight and systolic blood pressures of 5-week-old SHR and DRY rats were not significantly different. NHE-3 activity was higher in SHR, 1.08 +/- 0.1 pH units/min compared with DRY rats, 0.73 +/- 0.1 pH units/min (P < 0.05) H+-ATPase activity was also higher in SHR, 0.119 +/- 0.02 pH units/min, compared with DRY rats, 0.051 +/- 0.02 pH units/min (P < 0.05). CONCLUSIONS: Proximal tubule cells of 5-week-old SHR have higher NHE-3 and H+-ATPase activities compared with age-matched DRY rats. Enhanced proximal tubular fluid reabsorption is likely to contribute to development of high blood pressure in young SHR.

Animals↗

Comparative effects of three resistant starch preparations on transit time and short-chain fatty acid production in rats.

A high-fiber diet may protect against colon cancer because of the butyrate generated in the colon by bacterial fermentation of nonstarch polysaccharides. Butryrate can reverse neoplastic changes, at least in vitro, and resistant starch (RS) represents a source of butyrate in vivo. We examined the effects of replacing normal maize starch in the diet of rats with three preparations of RS on the amounts of starch, butyrate, and other short-chain fatty acids in the cecum. We examined the effects on fecal bulking and transit time, which have been suggested to protect against colon cancer. The RS preparations that we tested were potato starch, high-amylose maize starch, and an alpha-amylase-treated high-amylose maize starch. All had major effects on fecal weight and on the weight of the cecum but only slightly shortened transit times. All increased the amount of starch reaching the cecum and increased short-chain fatty acid production in the cecum; potato starch had the greatest effect and high-amylose maize starch the least. Potato starch, unlike high-amylose maize starch, enhanced the proportion of butyrate. Thus there were marked differences among sources of RS, even though these were all classified as RS2. The significance for colon cancer is discussed.

Animals↗

Ethanol effects on cardiomyocyte contractility.

Little is known about the direct cardiac effects of socially common sub-intoxication levels of ethanol. Previous studies evaluating the responses of normal cardiomyocytes to short-term ethanol exposure have utilized ethanol concentrations equivalent to extreme intoxication or lethal levels in vivo. The purpose of the present study was to investigate the contractile responses of isolated rat ventricular cardiomyocytes during exposure to relatively low concentrations of ethanol in the range 0.05-0.5% (v/v) (8.6-86 mM) under physiological conditions (3 Hz stimulation; 36 degrees C; BSA vehicle). High-speed imaging techniques were used to study the kinetics of myocyte contraction, and shortening parameters were calculated for mechanistic evaluation. The concentration-response relationship was not linear and exhibited two plateau phases, suggesting at least two mechanisms of action of ethanol on cardiomyocyte contraction. At 0.05% (8.6 mM), ethanol treatment produced a 14.4% decrease in maximum myocyte shortening. The maximum rates of cell shortening and lengthening were similarly impaired, but there was no effect on contraction cycle timing at this low concentration. At 0.30% (51 mM), ethanol reduced maximum shortening by 40.2%, prolonged excitation-contraction coupling latency and abbreviated the contraction cycle time by 38%. The inotropic modulatory effect of ethanol was exaggerated in the absence of protein in the superfusion buffer. This is the first report which identifies ethanol at 0.05% (v/v) as a modulator of cardiac contractility. Kinetic analyses indicate that the mechanism of action involves disturbance of sarcoplasmic reticulum function, and this may contribute to arrhythmogenic vulnerability - especially in an in vivo context of heightened compensatory sympathetic drive.

Animals↗

The effects of angiotensin II on blood perfusion in the rat renal papilla.

1. Systemic infusion of angiotensin II (AII) increased papillary blood perfusion (PBP) measured by laser-Doppler flowmetry in rats, aged about 5 weeks. 2. The mechanisms involved in this response were determined by infusion of AII in the presence of systemic doses of losartan (a type 1 AII receptor antagonist), HOE-140 (a bradykinin B2 receptor antagonist), and an inhibitor of NO production - Nomega-nitro-L-arginine (NOLA). 3. Mean arterial blood pressure (MAP) and PBP increased in a dose-dependent manner in response to intravenous infusions of AII. Infusion of losartan abolished these responses to AII but HOE-140 was without effect. Infusion of NOLA abolished the increase in PBP but did not affect the pressor response to AII. Systemic infusion of sodium nitroprusside restored the response to AII in experiments with NOLA infusion. 4. The results indicate that the increase in PBP caused by AII is mediated via angiotensin AT1 receptors and does not involve bradykinin B2 receptors. The AII-induced increase in PBP is dependent upon the presence of NO, thus providing a mechanism for maintenance of papillary perfusion in the face of generalized renal vasoconstriction due to AII.

Angiotensin II↗

Dietary fibres may protect or enhance carcinogenesis.

Dietary fibre (DF) is widely considered to protect against cancer, especially colorectal cancer. However, a large prospective epidemiological study has shown no apparent effect of DF intake on the development of colorectal cancer. We suggest that this may be because the term DF represents a wide range of materials, some able to protect, but some able to enhance carcinogenesis. This is consistent with data from animal carcinogenesis experiments. Most of the DF in western diets is in the form of plant cell walls, but these vary in their composition and it is unlikely that all types are protective. The few data available indicate that plant cell walls containing suberin or lignin may be the most protective, although they are present in only small amounts in food plants. DFs are also added to foods. These include components obtained from plant cell walls, such as pectins, as well as soluble DFs from other sources. In general, animal carcinogenesis experiments indicate that soluble DFs do not protect and some may enhance carcinogenesis. Few human intervention studies have been done on DF or sources of DF, with the exception of wheat bran, a good source of DF, which has been shown to protect. Possible mechanisms whereby DF may enhance carcinogenesis are discussed. In addition to DFs, resistant starches and non-digestible oligosaccharides are added to foods; these, like DF, escape digestion in the small intestine. However, so far only a few animal carcinogenesis experiments have been reported using these materials, and no human intervention studies. We believe caution should be exercised in the addition of such materials to food.

Animals↗

Imaging of renal medullary interstitial cells in situ by confocal fluorescence microscopy.

Renal medullary interstitial cells are a prevalent and characteristic feature of the inner medulla of the kidney, but the physiological significance of this is unclear. We have developed a method for imaging renal medullary interstitial cells in situ by loading the cells with fluorescent dyes and monitoring their distribution using confocal microscopy. The pH-sensitive probe 2'7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester was used as a marker of cytoplasmic volume and therefore of cell morphology. Nile Red was used to demonstrate the presence of renal medullary interstitial cell lipid droplets. Papillae were excised from 100 g Sprague-Dawley rats and loaded with the appropriate dye. The papillae were then examined using a Leica TCS 4D confocal microscope and oil immersion lenses. Fluorescence was excited (488 nm) using an argon laser and emission wavelengths above 515 nm collected using a long pass filter. Images of papillae loaded with 2'7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester clearly demonstrate a ladder-like arrangement of renal medullary interstitial cells. More detailed examination revealed the presence of cytoplasmic extensions that appear to make close contact with adjacent loops of Henle. Three-dimensional reconstructions of serial sections revealed spiral arrangements in some ladders of renal medullary interstitial cells. Nile Red-labelled lipid droplets of 0.5-1.0 microm diameter were located throughout the cytoplasm of renal medullary interstitial cells and especially within the cytoplasmic extensions. These experiments highlight the ability of confocal microscopy to allow investigation of renal medullary interstitial cells in situ.

Animals↗

Effects of angiotensin II receptor blockade on proximal fluid uptake in the rat kidney.

Angiotensin II has a well described dose-dependent biphasic action on proximal tubule fluid uptake, although the concentration and effect of endogenous luminal angiotensin II remain controversial. Shrinking split-droplet micropuncture was used to examine the fluid uptake in response to the luminal application of three AT1 antagonists (losartan, EXP3174, candesartan). Addition of losartan at 10(-8) M decreased fluid uptake rate (Jva) by 17.5+/-2.2% (P<0.05). Luminal addition of EXP3174 at concentrations between 10(-9)-10(-5) M caused a dose-dependent decrease in fluid uptake, with a maximum decrease of 41.0+/-9.5% (P<0.01) at 10(-6) M. Candesartan also decreased fluid uptake, by 21.9+/-4.9% (P<0.05) at 10(-8) M and 23.6+/-5.5% (P<0.05) at 10(-5) M. All three antagonists at a low concentration (10(-8) M) decreased fluid uptake. EXP3174 and candesartan at a higher concentration (10(-5) M) also decreased fluid uptake in contrast to the previously reported effect of losartan. We conclude that the endogenous concentration of antiotensin II in the proximal luminal fluid is low and exerts a stimulatory effect on fluid absorption. Losartan at concentrations greater than 10(-6) M may have a non-selective action on fluid uptake.

Absorption↗

Studies on the mechanism of cancer protection by wheat bran: effects on the absorption, metabolism and excretion of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

We examined ways in which dietary supplements of wheat bran may protect against colon cancer. The effects of supplementing the diet of female Wistar rats with 10% wheat bran on the disposition and metabolism of the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) labelled with (14)C was determined. Our data show that the wheat bran had a major effect on both the distribution and metabolism of IQ. At a low dose of IQ (1 mg/kg), we unexpectedly found that up to 2 h after gavage there were higher concentrations of radioactivity in the plasma of rats fed wheat bran compared with the controls, but there were lower concentrations of radioactivity after 2 h. At a high dose of IQ (50 mg/kg), there were always lower concentrations of radioactivity in the plasma of rats fed wheat bran compared with the control rats. One of the most marked effects of wheat bran was apparently to significantly retard the metabolism of IQ in the plasma when this was fed at either dose. There were also differences between the rats fed wheat bran and the control in the concentrations and types of IQ metabolites in the urine.

Animals↗

Protection against cancer by wheat bran: role of dietary fibre and phytochemicals.

Human intervention and animal studies have shown that supplementing the diet with wheat bran can protect against the development of a range of cancers, especially those of the colon and breast. Wheat bran is a rich source of dietary fibres (plant cell walls) that have structures and compositions which indicate that they may protect against cancer. Nevertheless, dietary fibre makes up less than half of wheat bran. Other nutrients and phytochemicals are present in wheat bran, some of which may also protect against cancer. These include phytic acid and various phenolic components such as phenolic acids, lignans and flavonoids. A major goal of future research on wheat bran should be to determine the relative roles in cancer prevention of the different components in wheat bran.

Animals↗