Edwin Bret Hart, 1874-1952: a brief biography.
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Biomedical subjects
Publications and source records attributed to J J Rutledge.
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A modification of Whitten's medium, involving a reduced content of Na-lactate syrup (0.2 ml/100 ml; 11.65 mM) and osmolarity (251 mOsm), was compared with normal Whitten's medium (0.37 ml/100 ml; 21.6 mM) for ability to support mouse embryonic development in vitro from one-cell to the blastocyst stage. In a pilot study utilizing 10 ICR donor female mice, in vitro developmental capacity (IVDC; percentage of fertilized one-cell embryos developing to blastocysts in vitro per female donor) was significantly enhanced by the modified medium (68.0 versus 24.0%; P<0.001). In the main study, utilizing 134 ICR and 17 ICR x C57BL/6J F(1) donor females, the modified medium supported increased IVDC for both ICR (67.9 versus 51.1%; P<0.001) and F(1) females (98.5 versus 89.4%; P<0.05). A large degree of among donor-female variation in IVDC was observed for both media in the ICR stock (SD = 30.0). The beneficial role of the reduction of Na-lactate in Whitten's medium may be related to an improved provision of energy requirements for first cleavage and/or a more suitable osmolarity for development.
An experiment was conducted to test effects of prenatal and postnatal fraternity size (size of litter in which an individual develops prenatally or is reared postnatally) on ovarian development in mice. Fraternity size treatments were created by standardizing sizes of prenatal and postnatal fraternities in which mice were gestated and reared. Prenatal fraternity size was standardized by surgery on Day 9 of gestation to 6, 10, and 14 fetuses. Postnatal fraternity size was standardized by randomly assigning pups to litters of 5, 10, or 15 pups within 24 h of birth. Female pups were killed at either 3 or 20 wk of age and right ovaries were prepared for histology. Follicles were classified by size and morphology, and numbers of follicles in each class were tabulated. Interaction of postnatal fraternity size and age was observed for number of antral follicles (p less than 0.05). Mice reared in small postnatal fraternities had more antral follicles at weaning (3 wk) and fewer antral follicles at maturity (20 wk of age) than mice reared in large postnatal fraternities. No effect of either prenatal or postnatal fraternity size on other follicle populations was observed (p greater than 0.20). Numbers of Type 2 (primordial), Type 3a, and Type 3b follicles changed with age (p less than 0.01); numbers of primordial follicles declined with age, but numbers of Type 3a and 3b follicles increased. A hypothesis of a negative association between postnatal fraternity size and number of antral follicles at 3 wk of age was supported, but a hypothesis of a positive association between fraternity size and number of primordial follicles was not supported.
Hypotheses of a negative association between fraternity size (size of litter in which an individual develops prior to birth or is reared following birth) and ovulation rate or litter size were tested by examining reproduction of females born or reared in varying prenatal and postnatal fraternities. Gifts were randomly assigned to develop prenatally and be reared postnatal in small or large fraternities. Dams of experimental animals were randomly assigned to one of two prenatal fraternity size treatments, either unilateral oviductal ligation (to bear a small prenatal litter) or no ligation (to bear a normal prenatal litter). Whereas this did result in differences (P less than .01) in litter size at birth (small = 6.2 +/- .4 vs large = 9.6 +/- .9), there was considerable overlap in observed litter sizes between ligated and nonligated dams. Consequently, effects of prenatal fraternity size were examined by regression. Distinct differences in postnatal fraternity size were created by randomly assigning piglets to small (5 piglets) or large (10 piglets) postnatal fraternities within 24 h of birth. Differences in postnatal fraternity size were maintained through weaning at 3 wk (small = 4.9 +/- .1 vs large = 9.4 +/- .2). Weights at birth (regression of birth weight on prenatal fraternity size = -.07 +/- .02, P less than .01) and weaning (small = 6.09 +/- .15 vs large = 5.46 +/- .17 kg, P less than .01) were heavier for gilts from small prenatal and postnatal fraternities, respectively, compared with gilts from large fraternities. Effects of prenatal and postnatal size on BW did not persist following weaning (P greater than .20).
Effects of prenatal and postnatal fraternity size (size of litter in which an animal develops prior to birth or is reared following birth) on long-term reproduction were studied by rearing 178 female ICR mice in standardized prenatal and postnatal fraternities. Three levels of prenatal and postnatal fraternity sizes were used in a 3 x 3 factorial experiment. Prenatal fraternity size was standardized by selectively terminating fetal development in pregnant females carrying at least 14 conceptuses. Prenatal fraternities were standardized to either 6, 10 or 14 fetuses, and postnatal fraternities were standardized by randomly assigning individuals to nurse litters of 5, 10 or 15 pups. Prenatal fraternity size negatively affected average pup weight at birth (P less than .05) but had little subsequent effect on growth or reproduction. Postnatal fraternity size negatively affected weight at weaning (P less than .01), with mice reared in smaller postnatal fraternities being heavier than those reared in larger fraternities. Following weaning, mice reared in smaller fraternities gained weight less rapidly (P less than .01) but still tended to be heavier at maturity (P = .11). Vaginal opening occurred at older ages in females reared in larger postnatal litters (P less than .01). An interval mating system was used to examine fraternity size effects on long-term reproduction. Females were exposed to males six times at 8-wk intervals with initial mating at 7 wk of age. Postnatal fraternity size and age at mating jointly affected litter size (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of prenatal and postnatal fraternity size (size of litter in which an individual is reared) on age at vaginal opening, growth, and subsequent litter production were examined by rearing mice in standardized prenatal and postnatal fraternities in a 3 X 3 factorial design. Prenatal fraternity size was standardized by reducing litters of 14 or more to either 14, 10, or 6 fetuses on Day 9 of gestation. Postnatal fraternity size was standardized by assigning pups randomly to nurse in litters of 5, 10, or 15 pups within 24 h of birth. Both prenatal and postnatal fraternity size affected growth of the mice (p = 0.02 and p less than 0.01, respectively) with mice reared in small fraternities attaining greater weights throughout the study. Prenatal fraternity size had a negative linear effect on litter size at second parity and tended to have a positive linear effect on age at vaginal opening. Postnatal fraternity size affected age at vaginal opening (p less than 0.01), litter size at first parity (p less than 0.01), and litter size at second parity (p = 0.03). These effects were positive and linear for age at vaginal opening (p less than 0.01; small fraternity size associated with younger age at vaginal opening) and negative and linear for litter size at first and second parity (p less than 0.01 and p = 0.10, respectively; smaller fraternity size associated with larger litter size). There was no interaction between prenatal and postnatal fraternity size effects on age at vaginal opening or litter size (p greater than 0.20).
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Effects of normal growth regulation on components of phenotypic variance and covariance of body weight were examined in a cross-fostering study of growth between 2 and 10 wk of age in ICR randombred mice. Different early growth rates caused genetic, postnatal maternal and residual environmental variances to increase, but these variances were subsequently reduced by negative autocorrelation between early and later growth. Postnatal maternal variance continued to increase for about 1 wk after weaning but then decreased substantially. Genetic variance caused by preweaning growth followed a pattern of increase and decrease very similar to that of postnatal maternal variance, but this pattern was masked by new genetic variance. Normal growth regulation affects the magnitudes of genetic variances and serial autocorrelations . The timing of these changes suggests that regulation of cell numbers reduces variance near the end of exponential growth, but this may be obscured by subsequent increase in cell size. In contrast with earlier studies, we find that targeted growth reduces both genetically and environmentally determined differences among early growth trajectories. Final size may be determined by an antagonistic balance between early growth rate and age at initiation of puberty.
Weights and individual feed consumption collected on 160 beef, dairy and beef X dairy dams and their progeny were used to estimate several measures of lifetime cow efficiency. Dams were fed either a high or a low energy diet. Efficiency was expressed as the ratio of outputs to inputs. Outputs included progeny weaning weights plus cow salvage weight, and inputs were progeny creep feed consumption plus the dam's lifetime feed consumption. In the first approach, life cycle cow efficiency was estimated by expressing weight output as a ratio to feed inputs when weights and feed consumptions were weighted by their probabilities; probabilities were a function of age distribution and percentage calf crop in a theoretical herd consisting of 100 cows and 20 yearling replacement heifers. In the second approach, actual lifetime cow efficiency was estimated by expressing weight outputs as a ratio to feed inputs when all components were weighted equally. Both approaches included efficiency estimates calculated with and without cow salvage value. Dams receiving low energy diets generally had lifetime efficiencies equal or superior to those fed high energy diets in spite of older ages at calving. Dams on the high energy diet had greater salvage value, but did not wean calves of sufficient additional size to offset their own increased metabolizable energy (ME) intake. Dam breeds and breed crosses of smaller size tended to be more efficient than those of large size, demonstrating the effectiveness of mating small dams to large sire breeds for improving cow efficiency. Breeds calving at later ages were less efficient. Efficiency ratios improved as number of progeny weaned increased.
Several measures of life cycle cow efficiency were calculated using weights and individual feed consumptions recorded on 160 dams of beef, dairy and beef X dairy breeding and their progeny. Ratios of output to input were used to estimate efficiency, where outputs included weaning weights of progeny plus salvage value of the dam and inputs included creep feed consumed by progeny plus feed consumed by the dam over her entire lifetime. In one approach to estimating efficiency, inputs and outputs were weighted by probabilities that were a function of the cow herd age distribution and percentage calf crop in a theoretical herd. The second approach to estimating cow efficiency involved dividing the sum of the weights by the sum of the feed consumption values, with all pieces of information being given equal weighting. Relationships among efficiency estimates and various traits of dams and progeny were examined. Weights, heights, and weight:height ratios of dams at 240 d of age were not correlated significantly with subsequent efficiency of calf production, indicating that indirect selection for lifetime cow efficiency at an early age based on these traits would be ineffective. However, females exhibiting more efficient weight gains from 240 d to first calving tended to become more efficient dams. Correlations of efficiency with weight of dam at calving and at weaning were negative and generally highly significant. Height at withers was negatively related to efficiency. Ratio of weight to height indicated that fatter dams generally were less efficient. The effect of milk production on efficiency depended upon the breed combinations involved. Dams calving for the first time at an early age and continuing to calve at short intervals were superior in efficiency. Weaning rate was closely related to life cycle efficiency. Large negative correlations between efficiency and feed consumption of dams were observed, while correlations of efficiency with progeny weights and feed consumptions in individual parities tended to be positive though nonsignificant. However, correlations of efficiency with accumulative progeny weights and feed consumptions generally were significant.
Data from inbred lines, one (D) selected for part record rate of lay and the other (C) unselected for any trait, were analyzed. After 19 generations of continuous full sib matings, the C line showed significant decreases in part record egg number, 32-week egg weight, shell thickness, full record egg number and part record rate of lay but nonsignificant decreases in hatchability, full record rate of lay, and laying house mortality. Age at first egg, Haugh unit and mature body weight showed significant increases in this line. The D line was similar to the C line in its response to the same intensity of inbreeding for all traits except full record egg number, part record rate, and fertility, each of which showed a significant decrease, and Haugh unit and full record rate of lay, which showed nonsignificant increases. Results indicated that the small advantages selection conferred on the inbred line in part record rate of lay (the selection criterion), full record egg number, and full record rate of lay were accompanied by undesirable changes in other traits, resulting in later sexual maturity, larger body weight, lower Haugh unit, fertility, and hatchability compared with the unselected line.
The capacity to synthesize PRL and GH was studied in normal mice and in Snell and Ames dwarfs. In normal mice GH synthesis turned on dramatically between day 16-17 of gestation whereas PRL was not detectable throughout gestation or the first week of life, was barely detectable in 8-day-old mice and was clearly demonstrable by 12 days of age. However, transplantation of pituitaries from newborn mice into adult female hosts resulted in substantial PRL synthesis. Treatment of mice with DES at various ages showed that neonates failed to respond to the hormone; in older pups, an age-dependent increase in the magnitude of PRL synthesis was observed. There was a direct correlation between nuclear estrogen receptor levels and PRL cell function. Snell and Ames dwarf mice failed to synthesize PRL or GH at any stage of development, nor could we detect immunoreactive peptides which might represent mutant forms of the hormones. Our findings suggest that: (1) GH gene expression precedes that of PRL by about 2 weeks; (2) the development of PRL cell function is dependent on estrogen; (3) the capacity to respond to estrogen is present before the endogenous initiation of PRL synthesis and is limited by the availability of estrogen receptor; and (4) in Snell and Ames mutants, both types of alleles result in failure of the pituitary to initiate PRL and GH synthesis.
Eight experiments were conducted to examine the influence of the conceptus on luteal function in mice. In uterine intact pseudopregnant mice, exogenous treatment with placental extracts or pregnant mouse plasma from Day 8 or Day 10 of gestation did not prolong the life span of the corpora lutea (CL). The interestrous interval (IEI) of hysterectomized pseudopregnant mice was extended by treatment with Day 10 placental extract and was accompanied by elevated plasma progesterone, consistent with the luteotropic nature of the Day 10 conceptus. The IEI of uterine intact pseudopregnant mice was prolonged by the presence of ectopically developing blastocysts and was further extended by a treatment with Day 10 placental extracts but not by treatment with Day 8 placental extracts. Although the ectopic blastocyst delayed the effect of the uterine luteolytic mechanism, there was no indication of luteotropic activity: the ectopic blastocysts were unable to activate the CL of the estrous cycle. In addition, plasma progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured in pseudopregnant, hysterectomized pseudopregnant and pregnant mice on Day 2 through 13 post-mating. The results of these experiments suggest a two-step mechanism in prolonging luteal function during pregnancy which involves two different substances. This mechanism involves an initial signal from the conceptus which blocks the uterine luteolytic mechanism and a subsequent luteotropic stimulus from the Day 10 conceptus which extends luteal life span to approximately the length of gestation.
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Hysterectomized pseudopregnant mice had plasma progesterone concentrations on Days 6, 8, 10 or 12 after mating that were greater (P less than 0.05) than those of intact pseudopregnant mice and lower (P less than 0.01) than those of pregnant mice. Concentrations of 13,14-dihydro-15-keto-prostaglandin F-2 alpha on Days 6, 7, 8, 9 or 10 after mating were lower (P less than 0.05) in pregnant and higher (P less than 0.01) in intact pseudopregnant mice than in hysterectomized pseudopregnant mice. The results support the conclusion that there are uterine and extra-uterine luteolytic mechanisms which are mediated by prostaglandin and are perhaps functional by Day 6 of pregnancy.
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The genetic change from multiple-trait selection experiments can be equated to the regression of genotype on phenotype. This gives rise to a method of obtaining estimates of additive genetic variances and covariances. The method requires the use of selection weights, derived by means of the index-in-retrospect, to provide invariant solutions. Solution variance estimates obtained from Monte Carlo simulation do not agree with variance estimates from ordinary least squares methods. This indicates that the errors are distributed with some structure V. A form of V is proposed which utilizes knowledge of the errors. Monte Carlo variance estimates from generalized least squares (GLS) methods agree closely with the average variance estimates from GLS when the proposed V is used. Use of an estimated V, derived after the initial estimation procedure, is shown to provide adequate information on the variance of the estimates.