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Biomedical subjects

M Ivan

Publications and source records attributed to M Ivan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Spontaneous de-differentiation correlates with extended lifespan in transformed thyroid epithelial cells: an epigenetic mechanism of tumour progression?

Normal thyroid follicular cells, like many highly differentiated epithelia, have limited proliferative capacity. We previously showed that this could be extended by expression of the SV40 large T oncogene, but that immortal lines always lost thyroid-specific differentiation. Detailed analysis now show that clones expressing T undergo 2 mutually exclusive fates. They either (i) remain well-differentiated, in which case they undergo irreversible growth arrest after 5 to 15 p.d., or (ii) spontaneously develop poorly differentiated sub-clones that exhibit greatly extended proliferative life spans (up to 75 p.d.). The frequency of this event (> 3 per 10(4) cell divisions) greatly exceeds that expected from somatic mutation, suggesting an epigenetic basis. This is supported by our finding of rare de-differentiated epithelial cells in normal thyroid that all generate clones with extended life spans, indistinguishable from the above, following introduction of SV40 T. Escape from early mortality in differentiated thyroid epithelium therefore requires not only loss of tumour suppressor gene function (induced here by SV40 T), but also a switch in differentiation programme, with the latter effectively converting the follicular cell into a cell type with increased intrinsic proliferative potential. The analogy between this in vitro model and the progression of thyroid cancer from the well-differentiated to the highly aggressive, anaplastic form suggests that de-differentiation may play a causal rather than a passive role in this critical switch in tumour behaviour.

Antigens, Viral, Tumor↗
PubMed1996

Mitogenic stimulation of normal and oncogene-transformed human thyroid epithelial cells by hepatocyte growth factor.

Hepatocyte growth factor (HGF) has been shown to be mitogenic for a wide variety of epithelial cells, including recently, dog thyroid follicular cells. Here we have extended this work to human thyrocytes, and find that recombinant HGF stimulates DNA synthesis (proportion of cells in cell cycle S phase) in normal primary cells in monolayer, with an ED50 of approximately 8 ng/ml and a maximum between 50 and 250 ng/ml. Stimulation was observed even in the presence of 10% fetal calf serum (previously the most potent mitogen for these cells in our hands), the maximum nuclear 3H-thymidine labelling index achieved with HGF being up to 6-fold higher than that with serum alone. A similar additive effect was observed on thyrocytes already stimulated to proliferate by expression of an activated ret oncogene. These results make HGF the most potent defined mitogen for human thyrocytes to date, and suggest that upregulated HGF/met signalling may confer a significant growth advantage even in neoplastic thyroid cells, consistent with the finding of increased met expression in many thyroid carcinomas.

Animals↗
PubMed1996

Duodenal flow of microbial and feed nitrogen in sheep fed normal soybean meal or soybean meal treated with modified zein.

The effect of protecting soybean meal from microbial degradation in the rumen on duodenal flow of microbial N and feed N was studied with sheep. The soybean meal was protected with chemically modified zein. Two groups of four wethers, each equipped with a ruminal cannula and a duodenal reentrant cannula, were fed a diet based on corn silage (1 kg of DM/d) that contained either a normal or protected soybean meal supplement. The results showed no appreciable differences between the two supplements in ruminal fluid pH, total N, and NAN concentrations; however, the concentration of total VFA was lower for protected soybean meal than for normal soybean meal. Although the flow of NAN into the duodenum was not affected, bacterial N flow was 18% lower, and feed N flow was 195% higher, for protected soybean meal than for normal soybean meal. The digestibilities of OM, ADF, and N in the digestive tract were not affected by the type of supplement. The treatment of soybean meal decreased the degradability of total feed N in the stomach by 22 percentage points, but the increased supply of feed N into the small intestine because of the treatment was at the expense of decreased bacterial synthesis of protein in the rumen, probably because of a shortage of RDP in the diet.

Animal Feed↗
PubMed1995

Effects of supplemental vitamins E and C on the immune responses of calves.

Two experiments were conducted to evaluate the effects of oral supplementation of vitamin C and vitamin E (alpha-tocopherol), alone and in combination, on immune responses of calves. In Experiment 1, 18 Holstein newborn female calves were supplemented with 0, 1, and 2 g/d of vitamin C from birth to 6 wk of age. Concentrations of ascorbic acid in blood plasma were significantly higher for supplemented calves than for control calves. No significant differences among treatments occurred in the concentrations of IgG1, IgG2, and titer to keyhole limpet hemocyanin. In Experiment 2, effects of oral supplementation of vitamins E and C on immune responses were studied using 18 Holstein female calves. Concentrations of alpha-tocopherol in blood plasma were significantly higher for supplemented than for control calves. The concentrations increased from birth to wk 1, and then very little change occurred from wk 1 to 6. Differences among treatments in the concentrations of IgG1, IgG2, IgM, and titer to keyhole limpet hemocyanin were not significant; however, concentrations of IgM in calves supplemented with vitamins E and C generally tended to be higher than those of control calves. Antibodies to keyhole limpet hemocyanin were higher at 6 wk than at 4 wk of age.

Animals↗
PubMed1994

Metabolism of tritiated D-alpha-tocopherol and D-alpha-tocopheryl succinate in intraruminally dosed sheep.

The comparative disposition (absorption, plasma disposition, tissue distribution) of D-alpha-tocopherol and of D-alpha-tocopheryl succinate (forms of vitamin E) was investigated in 10 ruminally cannulated wethers. Tritiated tocopherols (4 microCi/kg BW) were administered directly into the rumen. Plasma and ruminal fluid activity were regularly measured from the time of administration to 96 h after administration. Radioactivity in lymph was measured in four additional wethers dosed intraruminally (100 microCi) with the same tritiated compounds. Lymph was collected from the cannulated thoracic duct during the first 24 h after the administration. Wethers were killed and selected tissues were measured for their tocopherol activity. Plasma and ruminal fluid specific activity vs time were modeled using appropriate compartmental and noncompartmental approaches. It was shown that there was a large difference in the relative bioavailability of the two compounds with a four times higher (P < .05) relative availability of D-alpha-tocopherol than of D-alpha-tocopheryl succinate. This was explained in terms of incomplete hydrolysis of tocopheryl succinate before absorption. By direct ruminal fluid measurement, it was estimated that tocopherol behaves similarly to a soluble ruminal marker with a ruminal transit time of approximately 19 h. In plasma, the total mean residence time was 148 h for D-alpha-tocopherol and 106 h for D-alpha-tocopheryl succinate. The lymph activity was mainly associated with tocopherol both after tocopherol and tocopheryl succinate administration. Tissue concentration of radioactivity was higher (P < .05) for sheep dosed with tocopherol than for those dosed with the tocopheryl succinate, confirming the difference in bioavailability of the two compounds.

Animals↗
PubMed1994

In vivo and in vitro gastric emptying of milk replacers containing soybean proteins.

Gastric digestion of three milk replacers for which protein was provided either exclusively by milk powder or partially (50%) by heated soybean flour or soybean protein concentrate was studied in vivo and in vitro. In vivo gastric emptying of protein fractions of the diets was measured in six preruminant calves fitted with reentrant duodenal cannulas and used in a double 3 x 3 Latin square design. In vitro gastric emptying was studied after hydrochloric acid and rennet digestion in an artificial stomach. In vivo and in vitro flow rates of 12% TCA-insoluble N and total N were higher for the soybean diets than for the milk protein diet, indicating that the incorporation of soybean protein prevented casein from clotting. Because of this faster gastric emptying, proteolysis in the stomach was reduced. However, gastric emptying of NPN (12% TCA-soluble N) was significantly decreased only in vitro. No difference existed between the two milk replacers containing either soybean flour or soybean protein concentrate. In vivo and in vitro results were correlated, suggesting that the in vitro method could be used to predict gastric digestion of protein fractions in vivo.

Animal Feed↗
PubMed1993

A variant epithelial sub-population in normal thyroid with high proliferative capacity in vitro.

We describe the existence in normal human primary thyroid cultures of a hitherto unrecognised sub-population of epithelial cells. This variant phenotype is characterised by squamoid morphology, absence of thyroglobulin, and an altered profile of intermediate filament expression. We suggest that these cells are derived from scattered foci of squamous metaplasia present in the normal gland. Although they are initially present at a frequency of less than 10(-4), their very high proliferative capacity enables them to outgrow the 'classical' follicular cells and confers a much increased capacity for gene transduction. Recognition of these cells is therefore crucial in the interpretation of long-term thyroid culture experiments and those involving in vitro gene transfer.

Biomarkers↗
PubMed1993

Liver biopsy in sheep.

Liver biopsies were performed in the same group of 16 sheep on 8 consecutive wk using an apparatus with a fibre optic continuous light source and a telescope. The sheep were placed in a sternal position on a special table constructed of metal pipes (3.8 cm diameter) and 4.5 cm spacing. Approximately 300 mg of fresh liver sample was removed from each sheep to be analyzed for copper or vitamin E.

Animals↗
PubMed1992

Plasma 1,25-dihydroxyvitamin D, insulin-like growth factor-1, calcium, magnesium and phosphorus concentrations in pregnant beef cows and calves from a herd with a known history of congenital joint laxity and dwarfism.

An investigation was undertaken to ascertain the possibility of a relationship between calcium, inorganic phosphorus, magnesium, 1,25-dihydroxyvitamin D [1,25(OH)2D], and insulin-like growth factor-1 (IGF-1) concentrations in blood plasma and occurrence of congenital joint laxity and dwarfism (CJLD) in young cattle. Pregnant cows were fed hay (30 cows) or grass silage (122 cows) during winter months (October 15 to calving in March). Blood samples were taken from cows on seven occasions during the experiment and 48 hours after calving, and from calves at birth, and at seven, 14 and 56 days old. Five per cent of calves born (six of 122) to cows fed grass silage and none born to cows fed hay were affected by CJLD. The diet and health status of calves were not significantly (P greater than 0.05) associated with the plasma concentration of 1,25(OH)2D. The plasma calcium concentration declined with age of the calves (P less than 0.05) but was not affected by the occurrence of CJLD. Plasma phosphorus and magnesium concentrations in calves born to cows fed silage were higher (P less than 0.05) than in those born to cows fed hay. At birth and seven days old, plasma phosphorus concentrations were higher (P less than 0.05) in CJLD-affected calves than in healthy calves but the plasma concentration of IGF-1 was not different (P greater than 0.05). It was concluded that the high plasma phosphorus concentrations in CJLD-affected calves and their dams could be related to the aetiology of the CJLD condition in calves.

Animals↗
PubMed1992

Effects of bentonite on wool growth and nitrogen metabolism in fauna-free and faunated sheep.

Two experiments were carried out with sheep that originated from a fauna-free flock and were fed a soybean meal-corn silage diet with or without a bentonite supplement. One-half of the sheep fed each diet in each experiment were faunated with a mixed population of ruminal protozoa, whereas the other half of the sheep remained fauna-free until the end of both experiments. Wool growth and daily gain were measured in Exp. 1. (eight rams per treatment), which lasted 110 d, and the metabolic effects in the rumen and intestinal tract of protozoa and dietary bentonite supplement were tested with cannulated wethers (four wethers per treatment) in Exp. 2. The results of Exp. 1 showed decreased wool growth (P less than .05) due to the presence of protozoa in the rumen. Dietary supplementation with bentonite partly offset the decreased wool growth in sheep with protozoa, but there were no effects of dietary bentonite and no protozoa x bentonite interaction (P greater than .05). Daily gain was decreased by the dietary bentonite (P less than .05) supplement but was not affected (P greater than .05) by the ruminal presence of protozoa. In Exp. 2, protozoa increased (P less than .01) the ruminal concentrations of ammonia and decreased (P less than .05) the acetic:propionic acid molar ratio. Fractionation of N in the duodenal digesta flowing from the stomach to the small intestine showed that protozoa decreased (P less than .05) the flow of nonammonia N and bacterial N, and there was a protozoa x bentonite interaction for these effects (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Biokinetics and biliary excretion of radiotocopherol administered orally to sheep.

Four adult sheep were given .4 microCi/kg of BW of D-alpha[5-Me-3H]tocopherol orally. Plasma alpha-tocopherol specific activities were measured serially during a 72-h period, after which the sheep were killed. The disposition kinetics were best described by the use of a two-compartment model. The radiotocopherol had a slow distribution phase followed by a relatively slow elimination phase. During the 72-h period of serial monitoring the peak plasma specific activities were observed between 32 to 48 h. At slaughter (72 h after dosing) tissue radioactivity distribution indicated a high rate of accumulation in some glandular organs such as the liver and adrenals. Identification of radioactive components excreted in bile, using HPLC or thin-layer chromatography, showed that unchanged radiotocopherol was present only at very low concentrations (less than 3% of the total recovered radioactivity).

Administration, Oral↗
PubMed1992

Effects of bentonite and monensin on selected elements in the stomach and liver of fauna-free and faunated sheep.

Forty-eight rams, originating from a fauna-free flock, were divided into three groups of 16 and fed a corn silage-based diet that was unsupplemented (control) or included bentonite or monensin supplements. Eight rams in each group were inoculated with a mixed population of ruminal protozoa; the other rams remained free of protozoa throughout the 110-d experiment. The rams had free access to drinking water and assigned diet. All rams were killed at the end of the experiment, and ruminal and abomasal contents and livers were removed and sampled. Protozoal numbers in ruminal fluid of faunated rams were lower for groups fed bentonite or monensin supplements than for the control group. Bentonite decreased and monensin increased ruminal pH. The ruminal solubilities of Cu, Zn, and Mg were decreased by the presence of ruminal protozoa, but those of Fe, Mn, and Ca were not affected. Bentonite supplement decreased, and monensin supplement increased, the ruminal solubilities of Cu, Zn, and Mg. Protozoa increased the abomasal solubilities of Fe, but the other elements were not affected. Liver concentrations of Cu were decreased by bentonite and increased by monensin, but protozoa decreased the liver concentrations of both Cu and Mg. Liver concentration of Zn was affected by a monensin x protozoa interaction and that of Mg by a bentonite x protozoa interaction. It was concluded that chronic Cu poisoning could be accelerated by dietary supplements of monensin in sheep without ruminal microfauna, and the dietary Cu bioavailability could be decreased by dietary supplements of bentonite in sheep with a normal population of protozoa in the rumen.

Abomasum↗
PubMed1991

Plasma alpha-tocopherol profiles in sheep after oral administration of dl-alpha-tocopheryl acetate and d-alpha-tocopheryl polyethylene glycol-1000 succinate.

Twenty-five yearling wethers, weighing 45 to 50 kg, were used in a trial designed to compare the bioavailability of dl-alpha-tocopheryl acetate (TA) and d-alpha-tocopheryl polyethylene glycol-1000 succinate (TPGS). The sheep, five per treatment, were each given a basal diet without vitamin E supplement (control) or with a daily oral supplement of 240 iu TA or TPGS, or of 480 iu TA or TPGS. Blood samples were obtained at zero time, and then twice daily for three weeks. The bioavailability was greater for TA than for TPGS. This was indicated by the significantly higher (P less than 0.01) plasma alpha-tocopherol concentrations during the three-week experimental period in sheep dosed with equivalent units of TA than in those dosed with TPGS. When administered at 480 iu, the TPGS produced plasma profiles similar to those found after administration of the lower (240 iu) dose of the TA.

Administration, Oral↗
PubMed1991

Metabolic changes in the rumen following protozoal inoculation of fauna-free sheep fed a corn silage diet supplemented with casein or soybean meal.

Fauna-free wethers were fed bi-hourly a corn silage diet containing casein or soybean meal as a protein supplement. The wethers were inoculated via rumen cannula with a mixed population of ruminal ciliate protozoa. Ruminal fluid was sampled daily for 4 d before and for 13 d (and on d 28) after inoculation. Protozoal populations reached peak numbers on d 8 and decreased to new levels after d 9 for wethers on both supplements. Protozoa decreased (P less than 0.01) the concentrations of total volatile fatty acids, increased (P less than 0.01) the pH and decreased (P less than 0.01) he concentrations of total and non-ammonia nitrogen in ruminal fluid. The concentrations of ammonia nitrogen increased with increasing numbers of protozoa for wethers on both supplements, but the concentrations decreased after d 7 to approximately pre-inoculation levels for the casein-supplemented diet. The increasing numbers of protozoa were associated with the increased concentrations of total and free alpha-amino nitrogen (P less than 0.01) and sulfide (P less than 0.05) and with the decreased concentrations of soluble Cu (P less than 0.05) in the ruminal fluid in soybean meal-supplemented wethers but not in those receiving casein. It was concluded that dietary proteins with differing physical characteristics are metabolized to a different extent by ruminal ciliate protozoa, which in turn can affect the metabolism of other dietary nutrients such as nitrogen and sulfur and contribute to copper-sulfur interaction.

Ammonia↗
PubMed1990

Copper deficiency and posterior paralysis (Shalal) in small ruminants in the Sultanate of Oman.

A posterior ataxia or paralysis in goats and sheep is a syndrome known as Shalal within the Sultanate of Oman. An investigation was carried out into the etiology of the syndrome. Samples of blood and tissues were obtained from normal and Shalal-affected goats and sheep. Samples of feed were collected from the affected areas of the Sultanate. Chemical analyses of samples showed that affected animals suffered from severe copper deficiency in spite of sufficient copper contents in feed. However, concentrations of sulphur and iron in the feed were high. It was concluded that the Shalal syndrome in Oman is the condition generally known as swayback or enzootic ataxia caused by conditioned copper deficiency. The deficiency is probably due to copper-sulphur and copper-iron interactions in the rumen, enhanced by feeding of fresh roughage containing rumen degradable proteins.

Animal Feed↗
PubMed1990

Plasma vitamin E response in sheep dosed intraruminally or intraduodenally with various alpha-tocopherol compounds.

A total of 24 sheep were used to study two routes of vitamin E administration: intraruminal (IR) and intraduodenal (ID). For each route of administration, 12 sheep were divided into 3 groups of 4, and each group received one of the following vitamin E treatments (mg/kg body weight): treatment 1, D-alpha-tocopherol (60 mg); treatment 2, D-alpha-tocopherol acetate (70 mg); treatment 3, DL-alpha-tocopherol (90 mg). The results showed that two major indices of bioavailability, i.e. concentration maximum and the area under the plasma concentration time-curve, were higher following IR administration than ID administration for all three vitamin E compounds used in this experiment. In sheep dosed intraruminally no difference was observed between the three vitamin E preparations in their plasma vitamin E response. For the ID administration the peak of plasma vitamin E concentration was lower after D-alpha-tocopherol acetate dosing than with the other two preparations. The results indicated a beneficial effect of rumen environment on the availability of vitamin E supplements.

Animal Nutritional Physiological Phenomena↗
PubMed1990

Assessment of the role of manganese in congenital joint laxity and dwarfism in calves.

Pregnant beef cows were winter-fed (November 15 to calving) hay (24 cows), red clover silage (21 cows) or grass silage (52 cows). Blood samples were taken from each cow in December and February. A condition of congenital joint laxity and dwarfism was observed in 38% and 28% of calves born to cows fed red clover silage and grass silage, respectively. None of the calves born to hay-fed cows were affected by the condition. The congenital joint laxity and dwarfism was associated with a lower serum manganese concentration in silage-fed cows than in hay-fed cows. However, manganese concentrations were similar in red clover silage, grass silage and in hay. A lower bioavailability of manganese in silages other than in hay, resulting in an apparent manganese deficiency in silage-fed cows, is suggested as a possible factor contributing to the etiology of congenital joint laxity and dwarfism in calves.

Animal Feed↗