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Biomedical subjects

M Quinton

Publications and source records attributed to M Quinton.

16 recordsLinked to original sources
PubMed2004

Influence of tissue origins and external microenvironment on porcine foetal fibroblast growth, proliferative life span and genome stability.

One of the challenges of manipulating genes in primary cells is that the cells have a finite proliferation capacity. This, combined with the lower gene targeting efficiency of somatic cells, makes identification of targeted clones very difficult. The objective of this study was to establish a system that allows porcine foetal fibroblasts to reach their maximal proliferation capacity in vitro. The influence of fibroblast origin, stage of foetal development, cell seeding densities and concentration of foetal bovine serum (FBS) on the population doublings, the percentage of beta-galactosidase-activity-positive cells and the genome stability of foetal fibroblasts during in vitro culture was investigated. It was found that porcine foetal fibroblasts could be cultured for over 80 population doublings in the appropriate culture system. Fibroblasts from earlier stages of foetal development were better candidate cells than those from the later stages. Cells from the heart were more actively proliferative and more resistant to replicative senescence than those from the liver. Compared to 10% FBS content, 15% FBS provided better homeostatic support, not only to proliferative performance, but also in maintaining a normal karyotype. In addition, the proliferative life span of porcine foetal fibroblasts is also dependent on seeding density of the culture.

Animals↗
PubMed1999

Evaluation of three lines of immunodeficient mice for the study of spontaneous metastatic tumors.

Various immunodeficient animals have been used as transplantation recipients for studying the growth of human tumors. We have been assessing the value of immunodeficiencies for the study of naturally arising tumors, using a model system of transgenic mice that spontaneously develop cancer of the pancreas as a result of elastase promoter-driven expression of the large tumor antigen gene of simian virus 40. We previously reported the establishment of transgenic mice that carried the SCID and/or beige mutations, eliminating B- and T-cell function and reducing lytic NK cell activity, respectively. In SCID beige animals, metastasis rates and target organs for metastases were similar to those observed in humans with pancreatic cancer. We describe here analysis of subsequent more highly inbred generations of these mice. The data show that inbreeding has almost negated the value of these immunodeficiencies for enhancing disease progression, and we observe high rates of metastasis even in immunocompetent animals. The data suggest that SCID and beige immunodeficiencies may not always have the same value for the modeling of spontaneous tumors as they do for the study of xenografts.

Adenocarcinoma↗
PubMed1998

Natural killer cell frequency and function in Yorkshire pigs selectively bred for high or low antibody and cell-mediated immune response.

Porcine NK cells are small to medium-size lymphocytes having a variety of functions that may include the regulation of immune response. Thus frequency and function of NK cells were examined in generations 6 and 8 (G6, G8) of pigs selectively bred for high (H) and low (L) antibody and cell-mediated immune response (CMIR). Using the monoclonal antibody 5C6 as a pan NK phenotype marker and target cell binding and lysis as assays of function, it was found that H and L immune response pigs had high and low NK cell frequency, respectively, at G6 and G8. Function of NK cells differed by line, with the control (unselected) pigs being higher (with respect to target cell binding) or similar (with respect to lytic activity) to H which were higher than the L line pigs. Frequency of NK cells after primary immunization was in significant negative correlation with antibody after secondary immunization with hen egg white lysozyme (HEWL). Therefore, simultaneous selection for antibody and CMIR altered the frequency and function of NK cells in pigs with C > or = H > L.

Animals↗
PubMed1995

Comparison of evaluation-selection systems for maximizing genetic response at the same level of inbreeding.

Use of improved methods of genetic evaluation and intense selection lead to higher rates of genetic change but also lead to higher rates of inbreeding. A number of methods have been proposed to attain high rates of genetic response with moderate or low inbreeding (i.e., restrict the number of close relatives selected, use false high heritability in the genetic evaluation, use assortative mating, adjust estimated breeding values for the relationship with those already selected, avoid matings of related individuals, and increase the number of parents selected). These various methods were compared here using stochastic simulation of an infinitesimal genetic model. The results were studied graphically plotting response against inbreeding, so allowing comparison of the methods at each of a range of inbreeding levels. None of the methods was best over all conditions. At high rates of inbreeding and with a fixed number of sires, several of the methods gave large decreases in inbreeding for small losses in response. However, these were matched by simply increasing the number of sires selected. There is an optimum response-inbreeding "front" attained by several methods, and this front seems hard to breach. Characterization of the front would be useful in designing selection programs.

Algorithms↗
PubMed1994

Genetic response and inbreeding with different selection methods and mating designs for nucleus breeding programs of dairy cattle.

Stochastic simulation was used to study the effect of selection and mating strategy on rates of genetic response and inbreeding with a closed nucleus breeding program for juvenile and adult schemes with 8 males and 64 females selected to produce 1024 progeny (512 females). Selection strategies considered using all available information or only individual and sibling records. Selection of sires was either unrestricted or restricted to between full-sib families. The effect of avoidance of mating of relatives to limit inbreeding was also evaluated. Four mating designs were examined: each dam was mated to 1, 2, 4, or all sires. Mating designs involving one sire per dam and more than one dam per sire were referred to as hierarchical. Use of several mates per dam resulted in a factorial mating design. Selected parents were mated either randomly, best to best, or best to worst. An index based on relative inbreeding to response ratio was used to describe the effectiveness of strategies for reducing inbreeding relative to changes in rates of genetic response. Strategies that lower index values were preferred and include selection on BLUP or approximations of BLUP and factorial mating designs that involve the random mating of dams to several sires. Factorial mating designs were effective for a range of heritabilities. Avoidance of matings of full sibs and restriction of selection of sires to between full-sib families enabled appreciable reductions in the index. Nucleus breeding programs based entirely on the selection of juveniles were not indicated because they had higher index values than adult schemes.

Animals↗
PubMed1993

The effect of selection in sublines and crossing on genetic response and inbreeding.

More intense selection in a line gives greater genetic change but also gives a higher rate of inbreeding. Here, continuous selection in one line vs continuous selection in two or more sublines (for the same breeding objective and with the same total number of individuals tested) and crossing the sublines to reduce inbreeding, is studied by stochastic simulation using an infinitesimal model. On crossing, the inbreeding level in the cross, though zero, becomes equivalent to 1/n times that in the sublines, where n is the number of lines in the cross. In general, selecting in sublines and crossing gave less genetic response at the same level of inbreeding than selection in a single line. Use of the best subline generally gave less response than the whole line. It is concluded that selection response at the same level of inbreeding is greatest when all the test facilities and selection are concentrated in a single selection line.

Animals↗
PubMed1992

Comparison of selection methods at the same level of inbreeding.

Animal geneticists predict higher genetic responses to selection by increasing the accuracy of selection using BLUP with information on relatives. Comparison of different selection methods is usually made with the same total number tested and with the same number of parents and mating structure so as to give some acceptable (low) level of inbreeding. Use of family information by BLUP results in the individuals selected being more closely related, and the levels of inbreeding are increased, thereby breaking the original restriction on inbreeding. An alternative is to compare methods at the same level of inbreeding. This would allow more intense selection (fewer males selected) with the less accurate methods. Stochastic simulation shows that, at the same level of inbreeding, differences between the methods are much smaller than if inbreeding is unrestricted. If low to moderate inbreeding levels are targeted, as in a closed line of limited size, then selection on phenotype can yield higher genetic responses than selection on BLUP. Extra responses by BLUP are at the expense of extra inbreeding. The results derived here show that selection on BLUP of breeding values may not be optimal in all cases. Thus, current theory and teaching on selection methods are queried. Revision of the methodology and a reappraisal of the optimization results of selection theory are required.

Animals↗
PubMed1992

Estimation of effects of single genes on quantitative traits.

Studies involving the effects of single genes on quantitative traits may involve closed populations, selection may be practiced, and the quantitative trait of concern may also be influenced by background genes that are inherited in a polygenic manner. It is shown analytically that analysis of such data by ordinary least squares, the usual method of analysis, can lead to finding an excess of spurious significant effects of single genes, when no effect exists, for both randomly and directionally selected populations and can lead to bias in estimates of single-gene effects when selection has been practiced. The bias depends on heritability of the polygenic effects on the trait, selection intensity, mode of inheritance, magnitude of gene effect, gene frequency, and data structure. It is argued that when genotypes of individuals can be identified for all individuals with observations on the trait, use of mixed-model procedures under an animal model treating single-gene effects as fixed effects can provide unbiased estimates of single-gene effects and exact tests of associated hypotheses for pedigreed populations, even when selection is practiced. Results are illustrated through computer simulation.

Animals↗
PubMed1983

The acute toxicity of oxamniquine in rats; a sex-dependent hepatotoxicity.

Toxicity studies with oxamniquine in several laboratory animal species revealed an idiosyncratic sensitivity of rats, females being much more sensitive than males. After single p.o. doses of oxamniquine, rats died up to 14 days after the dose from hepatic failure. At doses near the LD-50, serum transaminases were high and proteins low from 24 h after the dose in females and from 48 h in males; serum and liver triglycerides showed no clear changes. Histologically the livers were characterised by cytoplasmic inclusion bodies, parenchymal necrosis, and bile duct proliferation. Metabolism and pharmacokinetic data were inadequate to explain the sex-dependency of this toxicity, but tissue distribution studies with carbon-14 labelled oxamniquine showed that 72 h after a given dose livers of female rats retained more label than males, and that little of this was due to unchanged drug.

Animals↗
PubMed1981

Techniques for the measurement of methotrexate in biological samples.

Techniques available for the measurement of methotrexate (MTX) in biological fluids are reviewed. The importance of measuring MTX in plasma following high-dose MTX treatment is now well recognized and renewed interest in the metabolism and pharmacokinetics of the drug has prompted the development of new techniques of analysis. Results obtained with our radioimmunoassay are presented and compared with results obtained by other methods.

Animals↗
PubMedDate not supplied

The relationship of right ventricular hypertrophy, right ventricular failure, and ascites to weight gain in broiler and roaster chickens.

Nine hundred twenty-five male progeny from 50 sire families of a commercial sire line were weighed at 14, 28, and 47 days and scored for right ventricular hypertrophydilation at 48 days. Broilers with marked hypertrophy of the right ventricle at processing (298 of 925) were significantly heavier than their more normal contemporaries at 14 and 28 days of age. These results suggest that rapidly growing broilers are more susceptible to increased pulmonary arterial pressure resulting in right ventricular hypertrophy, right ventricular failure, and ascites than slower-growing broilers. Thirty-five (3.5% of 997) broilers died from right ventricular failure and ascites, and 14 (1.5% of 925) has ascites at processing. Two hundred fifty-nine sibs were kept on full feed to 16 weeks of age. Between 7 and 16 weeks, 68 (26.3%) of these cockerels died from right ventricular failure and ascites and a further 27 (10.4%) had marked right ventricular hypertrophy-dilation when processed at 16 weeks. Thus most of the 298 broilers classified as having marked right ventricular hypertrophy at 7 weeks would likely have died from right ventricular failure and ascites if they had been kept on full feed until 16 weeks.

Animals↗