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Biomedical subjects

B W Kennedy

Publications and source records attributed to B W Kennedy.

At least 19 recordsLinked to original sources

Antibody avidity in Yorkshire pigs of high and low immune response groups.

Avidity indices of antibody to hen egg-white lysozyme (HEWL) were measured by chaotropic ion (SCN-) elution enzyme-linked immunosorbent assay (ELISA) in pigs grouped as high, control or low for various immune and innate resistance-related traits. The avidity index was the molar concentration of SCN- required to reduce by 50% the ELISA optical density value for a given serum. The index was independent of the amount of antibody. Eight- to ten-week-old Yorkshire pigs were immunized with HEWL and serum antibody measured by ELISA as one of five traits used to assign them to high, low or control response groups. Serum antibody avidity for HEWL was evaluated on Day 14 and Day 30 after primary (Day 0) and secondary (Day 14) immunization. The effects of response group, gender, litter, serum IgG concentration and anti-HEWL antibody on avidity were determined using a linear model. Antibody avidity indices varied amongst individuals. Mean avidity indices for sera collected on Days 14 and 30 were 0.61 +/- 0.43 and 1.22 +/- 0.56, with maximum indices of 2.64 and 2.86 respectively. Avidity of secondary response antibody was significantly higher (P less than or equal to 0.05). Pigs of the high response group had significantly higher secondary antibody avidity than those of the control (P less than or equal to 0.08) and low groups (P less than or equal to 0.01). Avidity index was positively correlated with antibody to HEWL on Days 14 and 30 but not to preimmunization serum IgG concentration or to other measured traits.

Animals

Hematological profiles in dairy cows treated with recombinant bovine somatotropin.

Recombinant bovine somatotropin (bST) was administered at 0, 10.3, or 20.6 mg per cow per day to 32 Holsteins for 38 wk. Fifteen currently treated cows had been treated in the previous lactation. Eighteen hematological variables and blood concentration of insulin-like growth factor I (IGF-I) were measured at five sample periods. The objectives of the study were to test the effects of bST treatments on hematological profiles and to relate blood IGF-I concentration to these variables. Results indicated little influence (P greater than .10) of previous bST treatments on hematological profiles measured in the current lactation. Current bST treatments, however, altered hematocrits (P = .10), mean corpuscular volume (P = .03), mean corpuscular hemoglobin (P = .009), and fraction of blood lymphocytes (P = .09). A week x bST treatment interaction also contributed to variation in hematocrit (P = .09), mean corpuscular hemoglobin (P = .05), fraction of neutrophils (P = .02), and fraction of lymphocytes (P = .04). Blood IGF-I concentration influenced fractions and counts of neutrophils (P = .06, .09), lymphocytes (P = .04, .02), and monocytes (P = .08, .05). Further in vivo and in vitro studies are warranted because this preliminary evidence suggests that bST and(or) IGF-I contribute to regulation of hematopoiesis in mature dairy cows.

Analysis of Variance

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

Effect of culling on selection response using phenotypic selection or best linear unbiased prediction of breeding values in small, closed herds of swine.

Records from 7,200 separate closed herds with either 12 or 25 sows that were mated to either four or eight boars per year were simulated by computer. Effects of selection method, herd size, and contemporary group variability on average genetic change, genetic variance, and inbreeding over 10 yr of selection were analyzed for traits with heritabilities of .1, .3, and .6. Selection of replacement animals was on individual phenotype or BLUP of breeding value using a reduced animal model. For both of these selection methods, two culling schemes were imposed: 1) based only on involuntary culling because of losses due to conception rate and age and 2) when an available replacement animal was projected to be superior to an existing breeding animal in the herd in addition to the involuntary culling. The contemporary group standard deviation was set at either .1 or .5 of a phenotypic standard deviation. Selection with BLUP gave 72, 36, and 12% more genetic improvement for heritabilities of .1, .3, and .6, respectively, than selection on individual phenotype after 10 yr. However, inbreeding increased 20 to 52% more rapidly and there was a decrease in genetic variance. Culling based on Scheme 2 increased genetic improvement over Scheme 1 by about 75% with coincident increases in inbreeding level and decreases in genetic variance. The largest changes in inbreeding and genetic variance were associated with culling on BLUP. Culling when a superior animal was available with individual phenotype had little effect on inbreeding and genetic variance. Use of four boars rather than eight boars and 25 rather than 12 sows per herd increased genetic response. Use of four boars also increased inbreeding and decreased genetic variance. Genetic variance was higher in herds with 25 sows, but the size of the sow herd had little effect on inbreeding. Contemporary group variation influenced only the genetic response of individual phenotypic selection with culling.

Animals

Contact sensitivity and systemic antibody responses in dairy cows treated with recombinant bovine somatotropin.

Effects of exogenous bST on humoral and cell-mediated immune responses in lactating dairy cows were determined. The systemic antibody response to human erythrocytes and the cutaneous sensitivity response induced by dinitrochlorobenzene were the immune responses investigated. Cows were treated with either 0, 10.3, or 20.6 mg of bST/d for 266 d starting between wk 4 and 5 of lactation. Systemic immunizations and contact sensitivity were initiated during midlactation, 22 wk after bST treatments began. Hemagglutinating antibody titers and areas under the response profiles were not statistically different for bST-treated versus control cows. The cutaneous sensitivity response was similarly not affected by bST administration. Present antibody titer results agreed with our previous observations that bST did not affect serum IgM concentrations, but the cutaneous sensitivity results were in contrast with our finding of augmented proliferative responsiveness of mitogen-stimulated peripheral blood lymphocytes in bST-treated versus control cows. It is possible that exogenous bST affects some immune processes and lymphocyte subsets and not others. Further research is required to determine the practical significance of the variable immunomodulation elicited by exogenous bST.

Analysis of Variance

Antibody avidity in swine lymphocyte antigen-defined miniature pigs.

Antibody avidity to hen egg white lysozyme (HEWL) was measured by thiocyanate ion elution enzyme-linked immunosorbent assay (ELISA) in swine lymphocyte antigen (SLA) defined miniature pigs. Serum antibody avidity was evaluated on day 14 and 30 after primary (day 0) and secondary (day 14) immunizations in eight to ten week old miniature pigs previously typed for swine lymphocyte antigen genotype. The effect of SLA genotype, litter, and gender on anti-HEWL antibody avidity was determined by least squares. Antibody avidity varied amongst individuals. Antibody avidity maturation was observed as a mean rise in antibody avidity from primary response (0.89 +/- 0.64) to secondary response (1.23 +/- 0.54) (p < 0.0005). Overall, SLA genotype did not significantly influence antibody avidity or avidity maturation, but pigs of dd genotype had greater avidity maturation between primary and secondary responses than other genotypes. Litter effects significantly affected antibody avidity and maturation.

Analysis of Variance

The effect of swine leukocyte antigen haplotype on birth and weaning weights in miniature pigs and the role of statistical analysis in this estimation.

Miniature pigs of seven swine leukocyte antigen (SLA) genotypes were examined for birth and weaning weights to determine the influence of major histocompatibility (MHC) and background genes on these traits. Effects of different statistical analyses on the magnitude of these associations also were examined. Data on 154 piglets from 32 litters were analyzed by least squares using a linear model that included effects of SLA, litter, and sex of piglet. In these miniature pigs, SLA genotype had little influence on birth and weaning weight; litter, which includes effects of background genes, had a significant effect on both birth weight (P less than or equal to .0001) and weaning (P less than or equal to .005) weight. When litter effects were not accounted for, SLA haplotype appeared to influence both birth (P less than or equal to .001) and weaning (P less than or equal to .10) weights. Use of simple group means, as opposed to least squares means, for comparisons of genotypes yielded misleading results. Simple means indicated that piglets with the aa genotype were heavier (P less than or equal to .01) at birth than those with the cd genotype; in contrast, least squares means showed that cd piglets were slightly heavier at birth (P less than or equal to .10). Heterosis was not observed for birth or weaning weights among piglets of various genotypes, nor did one vs two copies of any haplotype influence these traits.

Analysis of Variance

Genetic and environmental trends for litter size in swine.

Best linear unbiased predictors (BLUP) of breeding values for additive direct and additive maternal genetic effects were estimated from 3,944 purebred Yorkshire and Landrace first-parity litters recorded on the Quebec Record of Performance Sow Productivity Program and born between 1977 and 1987. Breeding values for gilts, dams, and sires were estimated using an individual animal model for measures of litter size of total number born (NOBN), number born alive (NOBA), and number weaned (NOWN). Environmental trends were estimated from average herd-year solutions, and genetic trends were estimated by regression of estimated breeding value on year of birth. Environmental trends were positive for all traits in both breeds but were significant only for NOWN in Landrace (.051 +/- .021 pigs/yr). Genetic trends were very small but were mainly negative for direct breeding value and combined direct and maternal breeding value. Significant estimates of genetic trends (P less than .05) were observed only within the Yorkshire breed, and these ranged from -.012 +/- .004 to .004 +/- .002 pigs/yr.

Age Factors

Influence of exogenous bovine somatotropin on the responsiveness of peripheral blood lymphocytes to mitogen.

Our objectives were to determine the effects of exogenous bovine somatotropin on peripheral blood lymphocyte responsiveness to mitogen and on concentrations of serum insulin-like growth factor-I and to determine whether a statistical relationship exists between these two variables. The cows on trial were treated with 0, 10.3, or 20.6 mg/d somatotropin, starting between wk 4 and 5 of lactation and continuing for 266 consecutive d. Lymphocyte proliferation (counts per minute) and concentration of insulin-like growth factor-I (nanograms per milliliter) were recorded from blood sampled at wk 3, 10, 26, 35, and 46 of lactation. The results showed that lymphocytes from the blood of treated cows responded to mitogen with higher proliferative responsiveness than cells from control cows, but that this effect required long-term treatment and adequate mitogen concentrations to be detected. The blood of treated cows also had elevated concentrations of insulin-like growth factor-I relative to that of control cows, but these were not statistically associated with the proliferative responsiveness of the peripheral blood lymphocytes to mitogen. Our results suggest that somatotropin has a role in the immune system of cows, but its mode of action and target tissues must be determined. Bovine somatotropin, injected at doses that increase milk yield, can augment cow immunity as judged by the proliferative responsiveness of peripheral blood lymphocytes in culture.

Analysis of Variance

Serum immunoglobulin profiles of dairy cows chronically treated with recombinant bovine somatotropin.

The objective of this study was to determine the effects of exogenous somatotropin on blood profiles of the major bovine Ig isotypes. Holsteins were treated with either 0, 10.3, or 20.6 mg recombinant bST/d. Subcutaneous injections were started between wk 4 and 5 of lactation and continued for 266 d. Blood samples were collected by coccygeal venipuncture throughout lactation for serum IgG, G1, G2, A, and M concentration determination. Cows treated with 10.3 mg of bST/d exhibited modest increases in mean blood concentrations of IgG (12.4%) and IgG2 (18.4%) relative to the other groups of cows. In addition, treated cows had 10.1% higher average concentration of IgA than controls. Somatotropin did not influence average lactational concentrations of IgG1 or IgM, although the group receiving 10.3 mg/d had higher late lactation concentrations of IgG1 than did the other two groups. However, treatment mean isotype concentrations were always within normal ranges, except for IgG2 from the 10.3 mg/d group, which were higher. The practical significance of elevated serum Ig concentrations observed in the present study is not known. However, the present data do show that bST administered at doses that increased milk yield had no apparent detrimental effect on humoral immunity as measured by blood concentrations of Ig.

Analysis of Variance

C. R. Henderson: the unfinished legacy.

Ideas and methods developed by Henderson have been applied widely to BLUP of additive genetic merit of animals and estimation of components of variance. However, a number of other contributions of Henderson to theory and application of animal breeding and statistics have not been as fully examined and exploited. Some of these contributions are complete in their own right and others lay the groundwork to help resolve remaining problems. Henderson had insight and made contributions to the areas of analysis of line and breed cross data, hypothesis testing under mixed linear models, prediction of breeding values with unknown variances, and selection models. The general flexibility of Henderson's mixed model methods to quantify a large variety of biological effects is also illustrated and discussed in light of new technologies in genetics and biology.

Animals

Minerals leached into drinking water from rubber stoppers.

Drinking water and its delivery system are potential sources of variation in animal research. Concern arose that rubber stoppers used to cork water bottles might be a source of some nutritionally required minerals which could leach into drinking water. Six types of stoppers, each having different compositions, were cleaned with stainless-steel sipper tubes inserted into them and attached to polypropylene bottles filled with either deionized water (pH 4.5) or acidified-deionized water (pH 2.5). After six days of contact, water levels of copper, magnesium, iron, manganese, zinc, chromium, and selenium were determined by atomic absorption spectroscopy. Additionally, three of the stopper types were analyzed for mineral content. Minerals were present in both stoppers and drinking water. Acidified-deionized water generally leached minerals from the stoppers than did deionized water. The black stopper which is commonly used in animal facilities contained and leached measurable levels of some minerals, but it still can be recommended for typical animal husbandry uses, although other types of stoppers would be more suitable for specific nutritional and toxicologic studies.

Animals

Efficiency of selection strategies for halothane-negative gene.

Use of a method to estimate the frequency of the halothane-negative allele in boars is illustrated for different sampling schemes for boar testing programs and for testing within closed breeding populations. This method uses information not only on the individual, but also on all mates and relatives including parents, siblings and offspring. Accuracy of the estimates of the allelic frequency in boars was measured through use of Monte Carlo simulation. The selection differential in real frequency of the halothane-negative allele when boars were selected on estimated allelic frequency was used as the criterion for accuracy. In the progeny testing situation, phenotypes of base boars and one generation of offspring were available. The average selection differentials with 90% selection (i.e., culling 10% of boars on estimated allelic frequency) when 2 and 10 litters of two boars each were tested were .017 and .044 in base boars and .013 and .025 in the offspring. The value of the boar's own phenotype was small. Higher selection differentials were found in the closed herd situation, where data on two generations were available. The selection differential in base boars when 10 litters were tested increased from .046 to .066 when the proportion of boars selected decreased from 90% to 50%. No improvement in selection differential with proportion selected was found in the progeny testing situation. Intense selection is most effective when the number of litters per boar is large and data over several generations are used. The estimation procedure for allelic frequencies in boars should improve current screening and selection programs to reduce halothane sensitivity in pigs.

Alleles

Estimation of direct and maternal genetic variance for litter size in Canadian Yorkshire and Landrace swine using an animal model.

Estimates of additive direct heritability (h2a) for traits such as litter size may be biased by maternal effects. The size of these effects was estimated using a derivative-free restricted maximum likelihood procedure under an animal model. First-parity records from Yorkshire (Y) and Landrace (L) gilts were obtained from the Quebec Record of Performance sow productivity program for 21,127 litters born between 1977 and 1987. Direct (sigma 2a) and maternal (sigma 2m) additive genetic variances, their covariance (sigma am) and error variance (sigma 2e) were estimated for total numbers born (NOBN), born alive (NOBA) and weaned (NOWN). Analysis of purebred Y and crossbred litters indicated that estimates of sigma 2a were of similar magnitude for all traits, with h2a ranging from .06 to .13. Except for L litters, estimates of sigma 2m were relatively low for NOBN and NOBA, and increased in size for NOWN, with h2m ranging from 0 to .08. Also, estimates of sigma am were negative, except for NOBN and NOBA with crossbred litters, and became increasingly negative for NOWN. Results from purebred L litters indicated there was a stronger negative correlation between direct and maternal genetic effects for NOBN and NOBA than for NOWN.

Analysis of Variance

Relationships between reproduction traits, age and body weight at calving, and days dry in first lactation Ayrshires and Holsteins.

Individual cow test day records collected between December 1979 and June 1986 were used to calculate measures of reproductive performance, age and weight at calving, and days dry for 7824 Ayrshire and 79,755 Holstein cows in first lactation. Separate analyses by breed were carried out according to a multiple-trait mixed model. Sixty-two Ayrshire and 369 Holstein sires were treated as random in the analyses. Ayrshires were, on average, older and lighter at calving than Holsteins, but the breeds differed little in reproduction measures and days dry. Heritabilities of fertility traits, days to first breeding, days open, and services per conception were all less than .015 in the multi-trait analyses. With the exception of body weight, heritability estimates for the other traits were less than .05. Phenotypic correlations between traits were almost identical for the two breeds, and genetic correlations tended to be similar. Exceptions involved the trait days to first breeding and services per conception, but heritabilities of these traits were close to zero (p less than .008) in Ayrshires. Fertility traits were positively correlated genetically. Genetic correlations between days open and both age and body weight at calving were small. The genetic correlation between age and weight at calving was -.90 and -.68 in Ayrshires and Holsteins, respectively. Genetic correlations between days dry and all traits except body weight were moderate and positive.

Aging

Simultaneous extraction of beta-endorphin and leu- and met-enkephalins from human and rat plasma.

A simple, rapid and reliable procedure is described to simultaneously concentrate and purify beta-endorphin, leu- and met-enkephalins from small volumes of human and rat plasma before radioimmunoassay is performed. It uses C18 Sep-Pak reverse phase cartridges. The effectiveness of different protease inhibitors in preventing degradation of opiates by plasma and different solvent systems for eluting opiates is also evaluated.

Animals