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Biomedical subjects

I L Cameron

Publications and source records attributed to I L Cameron.

At least 19 recordsLinked to original sources
PubMed1992

Dietary supplementation with pectin and guar gum on 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

The effect of dietary supplementation with pectin and/or guar gum on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied using 120 male Sprague-Dawley rats. The rats were given a weekly injection of DMH for 8 weeks and were maintained on a basal fiber-free diet supplemented with 5% cellulose. The rats were then subdivided into four groups and kept on the basal fiber-free diet supplemented with either no fiber, 10% pectin, 10% guar gum or a combination of 5% pectin/5% guar gum for a period of 24 weeks. The 8 weeks of DMH administration were defined as the initiation stage of carcinogenesis and the next 24 weeks were defined as the promotional stage of carcinogenesis. Food and water were available ad libitum. The rats were killed 32 weeks after the start of the experiment and tumor incidence, location and frequency in the colon were determined. Other parameters measured were body weight and caloric intake. Dietary fiber supplementation with 10% pectin or with 10% guar gum but not with the combination of 5% pectin/5% guar gum (fed during the promotional stage of carcinogenesis), was found to suppress colon cancer incidence to a significant extent.

1,2-Dimethylhydrazine↗
PubMed1992

New expressions to describe solution nonideal osmotic pressure, freezing point depression, and vapor pressure.

New empirical expressions for osmotic pressure, freezing point depression, and vapor pressure are proposed based on the concepts of volume occupancy and (or) hydration force. These expressions are in general inverse relationships in comparison to the standard ideal expressions for the same properties. The slopes of the new equations are determined by the molecular weight of the solute and known constants. The accuracy and precision of the molecular weights calculated from the slope are identical and approximately 1% for the experiments reported here. The nonideality of all three colligative expressions is described by a dimensionless constant called the solute-solvent interaction parameter I. The results on sucrose have the same I = 0.26 for all three solution properties. The nonideality parameter I increased from 0.26 on sucrose to 1.7 on hemoglobin to successfully describe the well-known nonideal response of macromolecules.

Animals↗
PubMed1992

Human and dog erythrocytes: relationship between cellular ATP levels, ATP consumption and potassium concentrations.

The intracellular K+/Na+ ratio of various mammalian cell types are known to differ remarkably. Particularly noteworthy is the fact that erythrocytes of different mammalian species contain entirely different potassium and sodium concentrations. The human erythrocyte is an example of the supposedly "normal" high potassium cell, while the dog erythrocyte contains ten times more sodium than potassium ions (Table I). Furthermore, this difference is sustained despite the plasma sodium and potassium concentrations being almost identical in both species (high Na+ and low K+). In spite of these inorganic ion differences, both human and dog erythrocytes contain 33% dry material (mostly Hb) and 67% water. Conventional cell theory would couple cellular volume regulation with Na+ and K+ dependent ATPase activity which is believed to control intracellular Na+/K+ concentrations. Since the high Na+ and low K+ contents of dog erythrocytes are believed to be due to the lack of the postulated Na/K-ATPase enzyme, they must presumably have an alternative mechanism of volume regulation, otherwise current ideas of membrane ATPase activity coupled volume regulation need serious reconsideration. The object of our investigation was to explore the relationship between ATPase activity, ATP levels and the Na+/K+ concentrations in human and dog erythrocytes. Our results indicate that the intracellular ATP level in erythrocytes correspond with their K+, Na+ content. They are discussed in relation to conventional membrane transport theory and also to Ling's "association-induction hypothesis", the latter proving to be a more useful basis on which to interpret results.

Adenosine Triphosphate↗
PubMed1991

Demonstration of the need for end point validation of putative biomarkers: failure of aberrant crypt foci to predict colon cancer incidence.

Seven-week-old Sprague-Dawley rats were fed a semipurified AIN76 diet and were given a weekly injection of the colon carcinogen 1,2-dimethylhydrazine for 8 weeks (initiation stage of carcinogenesis). The rats were divided into seven groups and each group of rats was placed on one of seven different modifications of the AIN76 diet for the next 24 weeks (promotional stage of carcinogenesis). The mean numbers of aberrant crypt foci/rat and the incidence of adenocarcinomas from some of the seven dietary groups were found to be significantly different. However, all attempts to show a significant correlation between the mean number of aberrant crypt foci/rat and the incidence of adenocarcinomas failed. Therefore, the number of aberrant crypt foci/rat cannot by itself be used as a reliable quantitative predictor (biomarker) of the efficacy of dietary intervention or of chemopreventive procedures on modulating the risk of developing colon cancer. This conclusion emphasizes the need for end point validation of potential cancer biomarkers before the biomarkers can be considered predictive of modulation of the risk for colon cancer.

Adenocarcinoma↗
PubMed1991

Proportional equilibration of K, Na ions, and sucrose molecules in pig lenses incubated in the presence of the non-ionic detergent Triton X-100.

The release of sodium and potassium and the uptake of sucrose molecules was studied in pig lenses incubated in isosmotic sucrose solution in either the presence or absence of 1% Triton X-100 (a non-ionic detergent). This Triton X-100 treatment has been shown to cause severe disruptions of cell membrane integrity. If sodium and potassium were free in the lens fibers as in a dilute aqueous solution, they would be expected to diffuse three to four times faster than sucrose. However, measurements of sodium and potassium release and sucrose uptake in the Triton X-100 treated lenses show a 1:1 equilibration. When pig lenses were incubated in the same solution without detergent, the sucrose uptake was significantly less than the potassium and sodium release. It is postulated that a slow, detergent mediated collapse of protein-water-ion interactions within the lens is the rate-limiting step of the observed equilibration of monovalent cations and sucrose molecules.

Animals↗
PubMed1991

Maintenance and mobility of hemoglobin and water within the human erythrocyte after detergent disruption of the plasma membrane.

Is an intact plasma membrane responsible for keeping hemoglobin and water within the human erythrocyte? If not, what is responsible? How free is Hb to move about within the erythrocyte? To answer these questions erythrocytes were taken for phase contrast microscopy, transmission electron microscopy (TEM), determination of water-holding capacity, and proton NMR studies both before and after membrane disruption with a nonionic detergent (Brij 58). Addition of 0.2% Brij to a D2O saline solution of hemoglobin (Hb) caused particles of Hb to appear and to aggregate. This aggregation of Hb caused the amplitude of the Hb proton NMR spectra to decrease. Thus, the less mobile the Hb the lower the Hb proton spectra amplitude. Erythrocytes washed in D2O saline showed proton NMR spectra of relatively low amplitude. Addition of Brij (0.2%) to these erythrocytes caused increased Hb mobility within these erythrocytes. The TEM of fixed and thin-sectioned erythrocytes treated with Brij showed disruption of the plasma membrane of all erythrocytes regardless of whether or not they had lost Hb. Brij-permeabilized erythrocytes washed in D2O saline or in a D2O K buffer maintained a higher heavy water-holding capacity upon centrifugation as compared to nonpermeabilized erythrocytes. The TEM of Brij-treated and washed erythrocyte "shells" revealed a continuous submembrane lamina but no other evidence of cytoskeletal elements. The water-holding capacity of the erythrocyte can be accounted for by the water-holding capacity of hemoglobin. The evidence favors a relatively immobile state of Hb and of water in the erythrocyte that is not immediately dependent on an intact plasma membrane but is attributed to interactions between Hb molecules and the submembrane lamina.

Body Water↗
PubMed1990

Influence of 60-Hz magnetic fields on sea urchin development.

Continuous exposure of sea urchin (Strongylocentrotus purpuratus) embryos at 18 degrees C to a cyclic 60-Hz magnetic field at 0.1 mT rms beginning 4 min after insemination caused a significant developmental delay during the subsequent 23 hours. No delay in development was recorded for periods up to 18 hours after fertilization. At 18 h, most embryos were in the mesenchyme blastula stage. At 23 h, most control embryos were in mid-gastrula whereas most magnetic-field-exposed embryos were in the early gastrula stage. Thus an estimated 1-h delay occurred between these developmental stages. The results are discussed in terms of possible magnetic-field modification of transcription as well as interference with cell migration during gastrulation. The present study extends and supports the growing body of information about potential effects of exposures to extremely-low-frequency (ELF) magnetic fields on developing organisms.

Animals↗
PubMed1990

Osmotic and motional properties of intracellular water as influenced by osmotic swelling and shrinkage of Xenopus oocytes.

Experiments were done on fully grown Xenopus oocytes to determine the extent and the properties of cellular water of hydration. The studies involved the osmotic shrinking and swelling of the oocytes under known osmotic pressure as well as proton NMR spectral, titration, and free induction decay analyses. Studies were done both on whole oocytes and on subcellular fractions. The results show that little if any of the oocyte water in situ has the motional or osmotic properties expected of pure "bulk" water. Four distinct water of hydration compartments were found and defined on the basis of distinct hydrogen bounding mechanisms. Some of the water in yolk platelets was found not to be in fast exchange with other water compartments. Osmotic shrinkage of oocytes caused an adaptive decrease in the bound water of hydration compartments. This osmotically induced decrease is attributed to decreased surface area available for the hydrogen bounding of water molecules on cellular proteins.

Animals↗
PubMed1990

Quantitative contribution of factors regulating rat colonic crypt epithelium: role of parenteral and enteral feeding, caloric intake, dietary cellulose level and the colon carcinogen DMH.

To elucidate the role and quantitative contribution of several exogenous factors which may regulate colon crypt mitotic activity, proliferative zone height (PZH) and crypt height, groups of rats were subjected to various feeding regimens both with and without treatment with the colon carcinogen, 1,2-dimethylhydrazine (DMH). The rats were divided into two major groups and one group was given eight weekly injections of DMH base at 9.5 mg kg-1 body weight. Throughout this period and for two additional weeks the rats were isocalorically fed either a defined nutritionally complete diet with different levels of dietary cellulose or they were parenterally (i.v.) fed a nutritionally complete liquid formula with different caloric levels. The rats were then injected with colchicine 3 h prior to sacrifice to arrest and to collect dividing cells at metaphase. The results of multiple regression analysis of all data were interpreted to indicate that parenteral feeding caused dramatic suppression of the colon crypt height (CH) and of the number of metaphase figures per crypt (MC). Increased cellulose intake stimulated CH but suppressed MC. The CH was also stimulated by DMH. CH was positively correlated to PZH and MC. The MC was suppressed by cellulose intake and negatively correlated to PZH but was positively correlated to CH. The PZH was positively correlated to CH. These findings were related to the role of luminal food, functional workload, kcal intake and treatment with DMH on the measured colon crypt parameters. A quantitative assessment of factors that regulate the measured colonic crypt parameters was accomplished.

1,2-Dimethylhydrazine↗
PubMed1990

A model to explain the osmotic pressure behavior of hemoglobin and serum albumin.

Previously published osmotic pressure data on hemoglobin and bovine serum albumin were used to determine the osmotically unresponsive solvent volume per unit dry mass of protein. A model is presented that accounts for the osmotic pressure of globular proteins based on a surface-associated osmotically unresponsive solvent volume. The model also accounts for changes in the osmotically unresponsive solvent volume owing to changes in pH, cosolute salt concentration, protein conformation, and protein aggregation.

Hemoglobins↗
PubMed1990

Evidence that a major portion of cellular potassium is "bound".

In this report we briefly review recent evidence which shows that a substantial proportion of intracellular K+ is "bound" or perturbed from the physicochemical properties expected in dilute aqueous solutions. In addition, we present evidence from electron probe x-ray microanalysis of thin cryosections of cells which indicates that the binding of K+ to anionic groups either carboxyl groups (HCO2) on proteins or to phosphate groups in creatine phosphate (CrP), in adenosine triphosphate, (ATP), in protein and in nucleic acids, are the main determinants of the maintenance of (as differentiated from the generated of) the well known intra- to extracellular K+ concentration difference. The collective evidence suggests that much of cellular K+ is reduced in its mobility and in its chemical activity due to association with negative charge groups (e.g. carboxyl and phosphates). This fact forces abandonment of the misleading assumption that the majority of intracellular K+ and other inorganic ions are as free as would be expected under ideal solution conditions. This realization should have far reaching consequences toward understanding transmembrane movement of water and solutes in cells.

Animals↗
PubMed1989

Effect of dietary cellulose on cell proliferation and progression of 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

The effects of different levels of dietary cellulose on colonic crypt mitotic activity and colon carcinogenesis were studied in 190 male Sprague-Dawley rats. Rats were divided into groups and fed a basal fiber-free diet supplemented with either 0, 5, or 15% pure cellulose (w/w), for periods of 10 weeks (initiation stage) or 32 weeks (promotional stage). Half of the rats in each group were given weekly s.c. injections of 9.5 mg 1,2-dimethylhydrazine (the base) (DMH) for 8 weeks. Some of the rats were killed at 10 weeks while most were killed 22 weeks later. In some groups the dietary cellulose level was changed to a different level at 10 weeks. Food intake and body weight data showed that the rats within each experiment were isocalorically fed. There was a direct correlation between crypt height and the percentage of cellulose in the diet. Addition of 5 or 15% dietary cellulose during the initiation stage of carcinogenesis resulted in a significant increase in crypt height. Increasing dietary cellulose after the initiation stage (0 to 5% and 5 to 15%) or maintaining a high dietary cellulose level throughout both the initiation and promotional stages (15%) resulted in a significant increase in crypt height. A DMH-induced increase in mitotic activity that was observed during the initiation stage was no longer evident after the 22-week promotional stage. The significant DMH-induced increases in proliferative zone height and crypt height that were initially observed during the initiation stage were also observed after the 22-week promotional stage. These data indicate that the initial DMH-induced increases observed in proliferative zone height and crypt height are irreversible. Addition of 5 or 15% cellulose was found to suppress DMH-enhanced mitotic activity in the crypts of the descending colon during the initiation stage of carcinogenesis. This finding was correlated with a significantly lower incidence of adenocarcinomas in rats maintained on 5 or 15% cellulose throughout both the initiation and promotional stages.

1,2-Dimethylhydrazine↗
PubMed1989

Suppression of a a carcinogen (1,2-dimethylhydrazine dihydrochloride)-induced increase in mitotic activity in the colonic crypts of rats by addition of dietary cellulose.

Serial injections of the colon carcinogen, 1,2-dimethylhydrazine (DMH), have been reported to increase the proliferative activity in the colonic crypts preceding development of tumors. Can addition of purified cellulose to a fiber-free AIN-76 rat diet be used to suppress this increase in proliferative activity? To answer this question rats were divided into two groups, and one group was given eight weekly injections of the DMH base at 9.5 mg/kg of body weight. Throughout this period and for 2 additional wk the rats were isocalorically fed a defined nutritionally complete diet both with and without different dietary levels of cellulose (0, 5, and 15%). The rats were given injections of colchicine 3 h prior to sacrifice to arrest and to collect dividing cells at metaphase. Analysis of variance was performed on various morphometric parameters obtained from histological sections of midaxial crypts from the descending colon. Our results confirm that DMH induced a significant increase in the mitotic activity as measured by the number of metaphase figures per crypt. The presence of dietary cellulose did cause a significant suppression of the DMH-induced increase in the crypt mitotic activity.

1,2-Dimethylhydrazine↗
PubMed1989

Cellular concentration of magnesium and other ions in relation to protein synthesis, cell proliferation and cancer.

This report concerns the possible regulatory roles of intracellular Mg, Na, K, Cl, H and Ca ions in protein synthesis, mitogenesis and oncogenesis. Our main approach was to measure the intracellular concentration of various ions in different mammalian tissue cell populations for correlation with the rate of protein synthesis, the rate of cell proliferation and the tumorigenic cell state. Mg concentration alone showed a significant positive correlation to protein synthetic rate, suggesting a key role for Mg in regulation of protein synthesis. All ions measured (Mg, Na, K, Cl) showed a significant positive correlation to the rate of cell proliferation in normal populations of tissue cells. Likewise rapidly dividing tumor cells showed markedly elevated concentrations of Na and Cl but not Mg and K. The tumor cells are therefore unique in terms of their ionic composition. The injection of tumorous mice with amiloride (a drug which blocks the passive influx of Na into cells and blocks the Na-H antiport process) lowered intracellular Na concentration without significantly changing the concentration of Mg or K in the rapidly dividing tumor cells. The cell proliferation rates of both normal and of tumor cell populations were decreased by this amiloride treatment. These data strongly suggest a regulatory role for Na and H concentration on the rate of cell proliferation in both normal and tumor cells. Recent reports have shown that a brief surge in free Ca occurs after mitogenic stimulation and at several other key points in the cell cycle. These findings suggest a signaling role for free Ca in cells. A model of the temporal sequence of ionic events in the cell cycle is presented. The report ends with a brief discussion of the role of ions in tumorigenic cell transformation.

Adult↗
PubMed1988

Extent and properties of nonbulk "bound" water in crystalline lens cells.

Crystalline lenses provided good material to study and measure the properties of cellular water. Different methods were used to establish the extent and properties of nonbulk water in mammalian lenses. These methods include: NMR titration analysis, a test of the osmotic properties, a test of dye exclusion In lenses with intact cell membranes and in lenses with disrupted cell membranes, and the water-holding capacity of lenses subjected to 40,000 x g for 1 hour with intact cell membranes and in lenses with disrupted cell membranes. The data from these methods, as well as other data from the literature, lead to the conclusion that most, if not all, of the water in lens cells (up to 2.2 g water/g dry mass) has motional and osmotic properties that distinguish it from bulk water. These findings call into question the common and convenient assumption that all but a small proportion of cellular water is like that in dilute solution.

Animals↗
PubMed1988

Role of plasma membrane and of cytomatrix in maintenance of intracellular to extracellular ion gradients in chicken erythrocytes.

Ultrastructural observations in combination with electron probe X-ray microanalysis on detergent (Brij 58) permeabilized (disruption of the plasma membrane) nucleated chicken erythrocytes support the view that a large fraction of cytoplasmic and nuclear K+ is not freely diffusible and that adsorption of K+ on detergent released mobilizable proteins exists within the cell. The data also suggest that the detergent proteins are normally immobilized by a detergent-resistant cytoskeleton so that they are not immediately free to diffuse from the cell for several minutes after detergent disruption of the plasma membrane.

Animals↗