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Biomedical subjects

I L Cameron

Publications and source records attributed to I L Cameron.

At least 109 records · Page 6Linked to original sources

Change in water proton relaxation time during erythrocyte maturation.

Erythrocyte populations from newborn and mature mice were characterized according to: size; ultrastructural features; water content; concentration of intraerythrocyte elements including Na, Cl, K, P, S, Mg, and Fe; and the spinlattice (T1) and spin-spin relaxation times of water protons as measured by nuclear magnetic resonance (NMR) spectroscopy. A significant increase in the T2 time from 142 +/- 3 msec to 184 +/- 3 msec occurred during erythrocyte maturation. This change in T2 time was correlated with a change from a polyribosome-rich hemoglobin-poor cell type to a polyribosome-absent hemoglobin-rich cell type. The change in T2 time could also be correlated to a significantly higher K and P concentration in the mature erythrocytes. The change in T2 time was not correlated to a change in cellular water content or to the concentration of any of the other elements measured by electron probe X-ray microanalysis. If the NMR relaxation times of water molecules truly reflect their average motional freedom, then the findings suggest that greater water ordering interaction occurs in the ribosome containing immature erythrocyte.

Animals↗

Intracellular elemental content of cardiac and skeletal muscle of normal and dystrophic hamsters.

To test the hypothesis that the genetic lesion causing muscular dystrophy might be reflected in an abnormal intracellular elemental content, the elemental content of individual cardiac and skeletal muscle fibers in 50-day-old male control and cardiomyopathic BIO 53.58 hamsters was determined. The technique of electron probe x-ray microanalysis of freeze-dried tissue was employed. No electrolyte content differences were found between control and diseased animals for nuclei, myofibrillar cytoplasm, or mitochondrially-enriched cytoplasm of cardiac myocytes. Sulfur was elevated in dystrophic cardiac myocytes and was the only element significantly different in heart tissue of control and cardiomyopathic animals. Sulfur was also elevated in dystrophic soleus muscle fibers. The pattern of electrolyte content of these cells reflected a mixture of normal cells and damaged cells with altered electrolyte content. In this hamster model, alteration of electrolyte content of myocytes appears to be a result of the disease process and not an inherent characteristic of muscular dystrophy. The elevated sulfur in dystrophic hamster myocytes reflects a biochemical lesion which deserves further study.

Animals↗

Assay for characterization of human follicular oocyte maturation inhibitor using Xenopus oocytes.

Human follicular fluid from healthy mature Graafian follicles and from pathologic ovarian cyst fluid was found to be inhibitory to progesterone-induced meiotic maturation of oocytes from the South African clawed toad, Xenopus laevis. Human follicular fluid but not human serum, collected from the same individuals, demonstrated a linear dose-response inhibition on the maturation of oocytes in the Xenopus assay system. These findings indicate that the human follicular and cyst fluids contain oocyte maturation inhibitor (OMI). This human OMI was inactivated when subjected to a boiling water bath for 2 min. The OMI action was shown to be reversible in its inhibitory action. The fact that OMI can act directly on the oocyte was demonstrated by its inhibitory action on maturation in defolliculated oocytes. The findings demonstrate that the inhibitory action of human OMI is not species-specific. Xenopus oocytes provide a simple, readily available, year-round bioassay material for testing follicular oocyte maturation inhibitor.

Animals↗

Parenteral level of glucose intake on glucose homeostasis, tumor growth, gluconeogenesis, and body composition in normal and tumor-bearing rats.

To determine the effects of different levels of glucose intake on glucose homeostasis, gluconeogenesis, body composition, and tumor growth, we gave 8 days of total parenteral feeding of a defined liquid formula diet to groups of Buffalo rats, with and without a transplantable Morris 7777 hepatoma. The level of glucose intake was held at levels which ranged from 0 to 9.5 g/100 body weight per day while the levels of all other nutrients were held constant. Measurements were made on tumor growth rate, terminal blood plasma glucose and whole blood lactate levels, gluconeogenesis, body and organ weight, muscle nitrogen content, liver glycogen, and urine analysis. Tumor-bearing rats (TB) at low glucose intake but not non-tumor-bearing rats (NTB) were found to be dependent on gluconeogenesis for maintenance of blood glucose homeostasis (normoglycemia). Body weight was dependent on glucose intake level in both TB and NTB rats with glucose intake rates of 5.7 g/100 g/day being the point between weight loss or gain. However, under these feeding conditions, tumor growth rate was not dependent on the glucose intake rate. The weight of epididymal fat pad and the size of fat cells were positively correlated with glucose intake rate in both TB and NTB rats, but the fat pad weight in TB rats showed a greater dependence on the rate of glucose intake than it did in the NTB rats. Glucose intake of 3.8 g/100 g/day or less leads to significant loss of muscle mass and loss of muscle nitrogen (protein) in TB but not in NTB rats. Some liver glycogen was detected in all groups of rats except those TB rats with zero glucose intake. TB rats with high glucose intake (5.7 to 9.5 g/100 g/day) had higher blood lactate and lower urine pH than did NTB rats. Thus, TB rats at low glucose intake (3.8 g/100 g/day or less), as opposed to NTB rats, demonstrated a significant dependence on gluconeogenesis for glucose homeostasis, mobilized more of their liver glycogen, and catabolized more of their muscle proteins to supply the increased energy needs of the growing tumor and to maintain normoglycemia.

Animals↗

Evidence for structuring of water in growing oocytes: an X-ray microanalysis and nuclear magnetic resonance study.

Energy dispersive X-ray microanalysis measured the Na, K, Cl, P, Mg, S and Ca contents (mM/kg dry weight) in the nucleus and yolk-free cytoplasm of growing Xenopus laevis oocytes quick frozen in the ovary. Nuclear magnetic resonance measurements of T2, the transverse relaxation time of water protons, were obtained on small immature oocytes and on large, fully grown oocytes. Changes in the nucleus and cytoplasmic content were observed for all elements except for Ca. Nuclear/cytoplasmic macroscopic gradients of K, Cl, Na, and Mg increase with growth. The T2 times of large oocytes were found to be shorter than those of small oocytes. The data in this report further support the hypothesis that intraoocytic water and elements do not exist in an ideal dilute solution and that changes in the states of water and elements occur during oocytic growth.

Animals↗

Effect of cancer cachexia and amiloride treatment on the intracellular sodium content in tissue cells.

This study was designed to investigate the effects of a growing H6 hepatoma on the intracellular element content in three distinctly different tissue cell populations of the mouse host (hepatocytes, fibroblasts, and crystal enterocytes). X-ray microanalysis measurements of the intranuclear concentrations of several elements (sodium, magnesium, phosphorus, sulfur, chlorine, and potassium) were made. Briefly, the tumor presence significantly increased intranuclear sodium concentration but not the concentration of magnesium, phosphorus, sulfur, chlorine, or potassium in three tissue cell types of mice that were anorectic and cachectic. A second aim of the study was to see if injections of the diuretic amiloride, a drug reported to block passive influx of sodium into mammalian cells, would counteract the effect of the tumor presence and lower the intranuclear concentration of sodium towards that of a non-tumor-bearing host. Amiloride did significantly lower the intranuclear level of sodium in the host tissues to that of non-tumor-bearing mice. The amiloride-caused decrease on intracellular sodium was correlated to a decreased cell proliferation activity in the tumor cells and duodenal enterocytes. A possible relationship between the intracellular concentration of sodium in tissue cells and cancer cachexia is discussed.

Amiloride↗

Effects of 1,2-dimethylhydrazine treatment and feeding regimen on rat colonic epithelial cell proliferation.

The present study was designed to test the hypothesis that 1,2-dimethylhydrazine dihydrochloride (DMH) induces preneoplasia in rat colonic epithelium and that this DMH-altered epithelium will respond differently to various nutritional challenges in comparison to normal colonic epithelium. Preneoplasia was arbitrarily defined as an altered and irreversible state of colonic epithelial cell proliferation induced by a carcinogen (DMH). In summary, DMH was found to be specific for the enhancement of rat colonic epithelial cell proliferation compared to other rapidly renewing cell populations, i.e., ileal epithelium and ear epidermis. DMH-induced changes in rat colonic epithelial cell proliferation and crypt cellularity were found to be irreversible following a 2- to 8-week recovery period. The p.o. administration of the solid and liquid diets, regardless of chemical constituents, supported a DMH-induced increase in colonic epithelial cell proliferation; however, a DMH-induced increase in epithelial cell proliferation was not observed in rats maintained on total parenteral nutrition. Thus, the route of administration has a significant influence on epithelial cell proliferation in colonic epithelium of DMH-treated rats. The importance of these results, along with previous studies, is the establishment and initial characterization of an exploitable preneoplastic system in rat colonic epithelium. Particularly revealing was the finding that significant changes in crypt kinetic parameters induced by DMH treatment did not revert to control values following a 2- to 8-week recovery period. Based on an altered and irreversible state of colonic epithelial cell proliferation induced by DMH, it is concluded that: (a) the preneoplastic state is a committed state and is not dependent upon the continued presence of the carcinogen; and (b) all cryptal epithelium is preneoplastic, although not all cells progress to the overtly transformed state. In addition, total parenteral nutrition prevented the expression of a DMH-induced preneoplastic state of altered epithelial cell proliferation.

1,2-Dimethylhydrazine↗

Effects of amiloride on tumor growth and intracellular element content of tumor cells in vivo.

The effects of amiloride, a reported inhibitor of serum-stimulated sodium influx, were tested on tumor growth, tumor cell proliferation, and intracellular element content of cancer cells in vivo. We have shown previously that cancer cells have high intranuclear levels of sodium compared to those of their normal counterpart cells and have postulated that such a high level of sodium may be involved in the cancer state. We now report that amiloride, when given in a series of injections, inhibited both H6 hepatoma and DMA/J mammary adenocarcinoma growth in vivo in a dose-dependent fashion and that 3 injections of amiloride at a dose of 1.0 microgram/g body weight into mice bearing H6 hepatomas resulted in a significant decrease in the intranuclear content of sodium but not the content of magnesium, phosphorus, sulfur, chlorine, or potassium as measured by electron probe X-ray microanalysis in the H6 hepatoma cells. Amiloride at dosages as low as 1.0 microgram/g body weight per injection also inhibited tumor cell proliferation as measured by the tritated thymidine autoradiography labeling index. Amiloride caused no changes in the mean profile diameters of metaphase or interphase H6 hepatoma or DMA/J mammary adenocarcinoma cells, suggesting that the action of amiloride on tumor growth was not due to cell volume changes. These data show that amiloride both inhibited tumor growth and decreased the proliferation of the tumor cells in the H6 hepatomas which was correlated with a decreased intranuclear sodium content.

Adenocarcinoma↗

Developmental changes in protein generation by cultured porcine granulosa cells.

1. The gross complement of proteins from porcine ovarian follicular fluid does not change as the follicles increase in size. 2. The electrophoretic profile of proteins from porcine follicular fluid is strikingly different from that of plasma proteins from the same animals. 3. Cultured granulosa cells from different sized follicles synthesize and release L-leucine-[3H]labeled proteins at different rates. 4. Cultured porcine granulosa cells appear capable of synthesizing most follicular fluid proteins.

Animals↗

Cell cycle-fluctuations in concentration of various elements in cytoplasm and in nucleus/chromatin of Physarum polycephalum.

The concentrations of Na, Mg, P, Cl, S, K, and Ca (m mol/kg dry wt) were measured during the cell cycle of P. polycephalum using electron-probe X-ray microanalysis. Significant cell cycle-associated fluctuations in the concentrations of all of these elements occurs in both the cytoplasm and the nucleus. In most cases the levels of each element were elevated during mitosis but greatly reduced during the S phase. Phosphorus and sulphur were concentrated in the nucleus/chromatin at metaphase. Ultrastructural analysis of these cells reveals a phase dependent variation in the density of the cytoplasmic ground substance which is most pronounced at mitosis. The changes seen in the cytoplasm occur not only in conjunction with the increased concentration of elements in the nucleus but also with the cessation of protoplasmic migration.

Cell Cycle↗

Evidence for turnover of DNA in the nucleus and in the cytoplasm of adult post-mitotic neurons in vivo.

Experiments were designed to determine if turnover of DNA occurs in post-mitotic neurons of adult mammals. Three-month-old laboratory mice, Mus musculus, and white footed mice, Peromyscus leucopus, were given three injections of 3H-thymidine (3H-TdR, 16 muCi/g body weight) at noon, 4 pm and 8 pm, and were killed serially beginning 1 h after the last injection. The brain stem was removed from the animals and autoradiographed. Some of the sections were treated with DNase prior to autoradiography. A sensitive and accurate method of autoradiographic grain count analysis was used to measure the grain counts over areas of neuron nuclei, neuron cytoplasm and background areas of the slide (Cameron, Pool and Hoage, 1979). There was a significant elevation of grains per unit area above background over both the nucleus and the cytoplasm in animals killed 24 h after the last 3H-TdR injection. Counts were reduced to background level by prior DNase treatment. This shows that the grains over the nucleus and the cytoplasm were due to label in the DNA. Changes in the grain counts with time were subjected to least squares regression analysis. In the mouse both the nucleus and the cytoplasmic grain counts showed a decreasing slope which was significantly different from a slope of zero when the data were fitted to either a linear model or a log-linear model. The data showed a somewhat better fit to the log-linear model. The labelled nuclear DNA in the mouse had a calculated half-life of about 502 h while the labelled cytoplasmic DNA had a calculated half-life of about 97 h. Our ability to measure and to characterize DNA turnover in specific in vivo cell types allows us to test theories about its functional role.

Animals↗

Elemental content in the nucleus and in yolk and yolk-free cytoplasm of developing Rana pipiens oocytes: an x-ray microanalysis study.

Energy dispersive x-ray microanalysis measured the Na, K, Cl, P, Mg, S, and Ca contents (mM/kg dry weight) in the nucleus, yolk-free cytoplasm, and yolk platelets of Rana pipiens oocytes quick frozen in the ovary. The data revealed that significant content changes occur in frog oocytes during intraovarian growth. All elements but Ca changed in content in the nucleus and cytoplasm, while in the yolk platelet only Na content did not change. A nucleus to cytoplasm K gradient develops and increases in magnitude during oocyte growth. The data from this and previous reports lead to the hypothesis that intra-oocytic water and elements undergo changes in state during oocyte growth and that three subcellular Na compartments exist.

Animals↗

Total parenteral nutrition for maintenance of growth, carcass mass and positive nitrogen balance in rats with a small transplantable tumor.

This study evaluates the effects of 13 days of total parenteral nutrition (TPN) on body weight, carcass mass and nitrogen balance in rats with and without a transplanted Morris No. 7777 hepatoma. Groups of rats without a tumor as well as rats with a tumor of about 3% of body weight or less were shown to maintain carcass weight as well as maintain a positive nitrogen balance when fed totally by vein. The present experiment was done under the same conditions as a previously reported experiment except that the size of the tumor in the rats was considerably smaller. These past studies showed that as the hepatoma gets much larger than 3% of the body weight, it was inhibitory to carcass weight gain even when the rats were given TPN. Thus, the size of the tumor influences the ability of TPN to sustain carcass weight.

Animals↗

The relation of keratinization to bacterial colonization on the baboon tongue as demonstrated by scanning electron microscopy.

Scanning electron microscopic observations of the baboon tongue demonstrating specificity of microbial distribution as related to epithelial keratinization are presented. The number of bacteria inhabiting a surface was related to the degree of keratinization. Orthokeratotic dorsal tongue surfaces were most heavily colonized by bacteria. The parakeratotic and non-keratinized surfaces were less heavily populated, with non-keratinized areas showing the fewest numbers of bacteria.

Animals↗

Effect of total parenteral nutrition on tumor-host responses in rats.

Total parenteral nutrition (TPN) is a clinical adjunct to cancer therapy. But it is difficult to do controlled clinical studies on cancer patients undergoing TPN. We therefore turned to a study of TPN on Buffalo strain rats with and without a Morris 7777 transplantable hepatoma. Our results showed that TPN at higher than normal levels (total parenteral hyperalimentation, abbreviated TPH) supported a gain in body weight of nontumorous rats. In tumorous rats, TPH supported body weight gain and stimulated tumor growth. Detailed analysis showed the TPH of the rats with a large rapidly growing hepatoma did gain body weight associated with fluid retention while the carcass weight decreased. Nor did TPH of tumorous rats significantly reverse the low cell proliferative activity to ear epidermis attributed to the tumor though it did stimulate tumor cell proliferation. Thus TPH by itself did not overcome wasting due to presence of the tumor. Using the hypothesis that uncontrolled gluconeogenesis is linked to cancer cachexia, we combined TPH with inhibition of gluconeogenesis (using hydrazine sulfate) and prevented the carcass weight loss (cachexia) in the tumorous rats. Tumor growth was stimulated by this treatment. Stimulation of cell proliferation in the tumor can, however, benefit chemotherapy using an S phase or cell cycle-specific cytotoxic drug.

Animals↗