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Biomedical subjects

R B Campbell

Publications and source records attributed to R B Campbell.

At least 19 recordsLinked to original sources

Exercise without dietary restriction as a means to long-term fat loss in the obese cardiac patient.

BACKGROUND: To examine the effects of a 12-month daily walking program without dietary restriction on the metabolic rate, body composition and blood lipid profile of overweight and moderately obese patients following myocardial infarction. METHODS DESIGN: longitudinal training (preliminary study). SETTING: out-patient cardiac rehabilitation program. PARTICIPANTS: twelve consecutive volunteers (8M, 4F) with a body mass index of 25-40 kg/m2. Relative to average cardiac patients, the men but not the women were significantly heavier (100.8 vs 77.4 kg [M], 70.7 vs 74.2 kg [F]) and fatter (hydrostatic estimate of body fat 34.0% vs 23.1% [M]; 38.3% vs 36.3% [F]) than the general cardiac patient. MEASURES: body mass, hydrostatic weighing, triglycerides, total, HDL- and LDL-cholesterol, resting and peak oxygen intake, one week food intake diaries. RESULTS: Daily walking increased progressively from 20 min to 43 min over 3 months, and was then held constant for 9 months. Peak aerobic power increased 24%, from 19.9 to 24.6 ml/[kg.min] (p < 0.001). Resting oxygen intake rose from 3.1 to 3.4 ml/[kg.min], (p < 0.05). Energy intake increased from 6.10 to 6.57 MJ/day, but body mass decreased by an average of 4.5 kg (p < 0.05, 4.1 kg [M], 5.1 kg [F]), and body fat content diminished from 35.4 to 33.2% (p < 0.02, 1.8% [M], 3.2% [F]), with no change in lean body mass (57.7 vs 57.8 kg). Triglycerides diminished from 2.63 to 2.28 mmol/L (p < 0.005). Total and LDL-cholesterol also tended to change favorably (from 6.15 to 5.80 and 4.44 to 3.80 mmol/L respectively, but HDL-cholesterol was unchanged). CONCLUSIONS: A daily walking program without dietary restriction induces a favorable change in body composition and lipid profile in moderately obese cardiac patients. An exercise-induced increase of resting metabolism apparently makes an important contribution to this outcome.

Body Composition

Influence of steroid injection on ligament healing in the rat.

The effect of a single local injection of long acting corticosteroid on the healing of acute rat medial collateral ligament injuries was studied. The medial collateral ligaments of 81 adult female rats were exposed surgically. In 32 rats, the ligament was transected sharply, the overlying muscle was closed, and a human equivalent dose of dexamethasone was injected under the muscle layer, bathing the injured ligament. The identical operation with no corticosteroid injection was done in 32 additional rats: in the remaining 17 animals, the incision was closed without ligament transection or injection. The rats were divided into 3 groups of 25. Each group consisted of 10 rats that were injected, 10 that were not injected, and 5 that underwent sham operations. One group was euthanized 6 days after surgery, 1 group after 10 days, and 1 group after 20 days. Histologic evaluation and biomechanical testing were performed for each subgroup. A cellular pathologist examined a smaller group of 6 rats (2 from each group) for histologic changes 40 days after surgery. No histologic differences were noted between the injected and noninjected ligaments 6, 10, or 20 days after injury. At 40 days, the injected specimens showed a slightly more mature crimp pattern than the noninjected specimens. Mechanical testing demonstrated no significant difference in ultimate load or ultimate stress between the injected and noninjected groups. There were no detrimental effects of a single dose administration of dexamethasone on the histologic appearance or biomechanical strength of healing rat medial collateral ligaments.

Animals

The effect of mating structure and progeny distribution on heterozygosity versus the number of alleles as measures of variation.

Heterozygosity and the number of alleles are both measures of the genetic variation of a population. They are qualitatively similar if the distribution of the number of progeny is Poisson, but not necessarily for other distributions. In particular, selfing decreases heterozygosity and also decreases the number of alleles when the progeny distribution is Poisson, but decreases heterozygosity and increases the number of alleles when there are two progeny per individual. This is because heterozygosity is closely related to the breeding structure (inbreeding) of the population, whereas the number of alleles is more influenced by the variation of the sampling process. Branching processes are employed to model the dynamics of mutant alleles, with drift and subsequent mutation contributing to extinction. In populations of four individuals, double first cousin mating has greater heterozygosity, but fewer alleles, than half-sib mating.

Alleles

Genetic interactions and dosage effects of Polycomb group genes of Drosophila.

The Polycomb (Pc) group of genes are required for maintenance of cell determination in Drosophila melanogaster. At least 11 Pc group genes have been described and there may be up to 40; all are required for normal regulation of homeotic genes, but as a group, their phenotypes are rather diverse. It has been suggested that the products of Pc group genes might be members of a heteromeric complex that acts to regulate the chromatin structure of target loci. We examined the phenotypes of adult flies heterozygous for every pairwise combination of Pc group genes in an attempt to subdivide the Pc group functionally. The results support the idea that Additional sex combs (Asx), Pc, Polycomblike (Pcl), Posterior sex combs (Psc), Sex combs on midleg (Scm), and Sex combs extra (Sce) have similar functions in some imaginal tissues. We show genetic interactions among extra sex combs (esc) and Asx, Enhancer of Pc, Pcl, Enhancer of zeste E(z), and super sex combs and reassess the idea that most Pc group genes function independently of esc. Most duplications of Pc group genes neither exhibit anterior transformations nor suppress the extra sex comb phenotype of Pc group mutations, suggesting that not all Pc group genes behave as predicted by the mass-action model. Surprisingly, duplications of E(z) enhance homeotic phenotypes of esc mutants. Flies with increasing doses of esc+ exhibit anterior transformations, but these are not enhanced by mutations in trithorax group genes. The results are discussed with respect to current models of Pc group function.

Alleles

Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster.

The Polycomb (Pc) group genes of Drosophila are negative regulators of homeotic genes, but individual loci have pleiotropic phenotypes. It has been suggested that Pc group genes might form a regulatory hierarchy, or might be members of a multimeric complex that obeys the law of mass action. Recently, it was shown that polyhomeotic (ph) immunoprecipitates in a multimeric complex that includes Pc. Here, we show that duplications of ph suppress homeotic transformations of Pc and Pcl, supporting a mass-action model for Pc group function. We crossed ph alleles to all members of the Polycomb group, and to E(Pc) and Su(z)2 to look for synergistic effects. We observed extragenic noncomplementation between ph503 and Pc, Psc1 and Su(z)2(1) in females, and between ph409 and Sce1, ScmD1 and E(z)1 mutations in males, suggesting that these gene products might interact directly with ph. Males hemizygous for a temperature-sensitive allele, ph2, are lethal when heterozygous with mutants in Asx, Pc, Pcl, Psc, Sce and Scm, and with E(Pc) and Su(z)2. Mutations in trithorax group genes were not able to suppress the lethality of ph2/Y; Psc1/+ males. ph2 was not lethal with extra sex combs, E(z), super sex combs (sxc) or l(4)102EFc heterozygotes, but did cause earlier lethality in embryos homozygous for E(z), sxc and l(4)102EFc. However, ph503 did not enhance homeotic phenotypes of esc heterozygotes derived from homozygous esc- mothers. We examined the embryonic phenotypes of ph2 embryos that were lethal when heterozygous or homozygous for other mutations. Based on this phenotypic analysis, we suggest that ph may perform different functions in conjunction with differing subsets of Pc group genes.

Alleles

Antagonism of estrogenic effects on feeding behavior by central implants of anisomycin.

The following experiment determined whether the estrogenic suppression of food intake is dependent upon changes in protein synthesis within neurons of the paraventricular nucleus of the hypothalamus (PVN). Ovariectomized rats were treated centrally with anisomycin-filled or empty (control) cannulae in the PVN. Females were injected with either 2.0 micrograms of estradiol benzoate (EB) or the oil vehicle and the inner cannulae were removed 2 h later. EB injections significantly lowered food and water intake in the central control group but not in animals given PVN implants of anisomycin. Body weight gain decreased for all females. EB induced comparable levels of female sexual behavior in both groups, demonstrating that anisomycin implants did not affect the ability of estradiol to stimulate lordosis. These findings indicate that the effects of estradiol on food intake require the activation of protein synthesis in estrogen-sensitive PVN neurons.

Animals

Half-sib mating structures.

All ways in which all matings in a population can be between half-sibs under a generalization of regular systems of inbreeding are characterized for both finite and infinite populations. A model of random half-sib mating is developed and analyzed, and the asymptotic configuration of populations subject to it is described. The classical model of half-sib mating which ensues from the standard definition of regular systems of inbreeding is only one of many ways a population can propagate by half-sib mating, and a wide range of genetic identity is possible dependent on which half-sib mating structure governs a population.

Animals

Genetic analysis of the additional sex combs locus of Drosophila melanogaster.

Additional sex combs (Asx) is a member of the Polycomb group of genes, which are thought to be required for maintenance of chromatin structure. To better understand the function of Asx, we have isolated nine new alleles, each of which acts like a gain of function mutation. Asx is required for normal determination of segment identity. AsxP1 shows an unusual phenotype in that anterior and posterior homeotic transformations are seen in the same individuals, suggesting that AsxP1 might upset chromatin structure in a way that makes both activation and repression of homeotic genes more difficult. Analysis of embryonic and adult phenotypes of Asx alleles suggests that Asx is required zygotically for determination of segment number and polarity. The expression pattern of even-skipped is altered in Asx mutant embryos, suggesting that Asx is required for normal expression of this gene. We have transposon-tagged the Asx gene, and can thus begin molecular analysis of its function.

Alleles

On the robustness of regular systems of inbreeding.

Half-sib, first cousin, half nth cousin, and nth cousin mating systems are robust in that small deviations from the mating structure will not significantly alter the levels of genetic identity or effect qualitative distinctions between the models. Substitution of nearest kin in matings may either increase or decrease the level of homozygosity depending on the mating structure; the effect of a single error in the mating structure is not an accurate indicator of the equilibrium resulting from recurrent errors. Models of mixed half nth cousin or nth cousin mating show that the relative frequency of the lowest order inbred mating essentially determines the level of homozygosity. Any positive relative frequency of more distant matings will reduce the probability of identity by descent under half-sib or first cousin mating to less than 1.

Alleles

Regular systems of inbreeding with mutation.

Probability of identity by type is studied for regular systems of inbreeding in the presence of mutation. Analytic results are presented for half-sib mating, first cousin mating, and half nth cousin mating under both infinite allele and two allele (back mutation) models. Reasonable rates of mutation do not provide significantly different results from probability of identity by descent in the absence of mutation. Homozygosity is higher under half-sib mating than under first cousin mating, but the expected number of copies of a gene in the population is higher under first cousin mating than under half-sib mating.

Genetics, Population

Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation.

We have tested the feasibility and effectiveness of a 2 year (average 16 +/- 7 months) walk/jog exercise program on 36 male orthotopic cardiac transplant patients (21 to 57 years old) seen initially 2 to 23 months after surgery. Comparison of initial exercise test results with those in 45 age-matched normal men showed the patients to have a lesser lean body mass (56 +/- 7 vs 63 +/- 8 kg, p less than .001), with a higher resting heart rate (104 +/- 12 vs 77 +/- 14 beats/min, p less than .001) and systolic (138 +/- 16 vs 129 +/- 17 mm Hg, p less than .001) and diastolic (95 +/- 14 vs 84 +/- 10 mm Hg, p less than .001) blood pressures. Peak power output was less than normal (101 +/- 27 vs 219 +/- 41 W, p less than .001), as was peak heart rate (136 +/- 15 vs 176 +/- 13 beats/min, p less than .001), peak oxygen intake (VO2max) (22 +/- 5 vs 34 +/- 6 ml.kg.min-1, p less than .001), and absolute anaerobic threshold (1.18 +/- 0.40 vs 2.04 +/- 0.40 liters.min-1, p less than .001). Peak ventilatory equivalent was higher (48 +/- 9 vs 37 +/- 61.1-1, p less than .001). Cardiac output (Q), as estimated by the CO2 rebreathing method, was slightly above normal at rest (p less than .01), but below normal at two submaximal work rates. The group's average weekly training distance was 24 km, with eight highly compliant patients progressing to 32 km or more weekly. After training, lean tissue increased (+2.4 +/- 3.1 kg, p less than .001), and resting values were reduced for heart rate (-4 +/- 11 beats/min, p less than .05), systolic (-13 +/- 20 mm Hg, p less than .001), and diastolic (-9 +/- 17 mm Hg, p less than .001) blood pressures. There were significant reductions in submaximal values for minute ventilation (VE), ratings of perceived exertion, and diastolic blood pressure at equivalent workloads. Peak values increased for power output (+49 +/- 34 W, p less than .001), VO2max (+4.0 +/- 6.0 ml.kg.min-1, p less than .001), VE (+20 +/- 20 l.min-1, p less than .001), and heart rate (+13 +/- 17 beats/min, p less than .001), and decreased for diastolic blood pressure (-8 +/- 15 mm Hg, p less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

The effects of genetic screening and assortative mating on lethal recessive-allele frequencies and homozygote incidence.

The widespread use of genetic screening, along with mating and reproductive patterns reflecting that information, can significantly alter the genetic structure of populations. Both allele frequencies and mortality could be significantly reduced if carriers of lethal recessive alleles were withdrawn from the mating pool. But schemes to mask deleterious alleles in heterozygous condition could significantly increase the deleterious-allele frequencies while resulting in only a slight reduction in mortality. The immediate and equilibrium consequences of such mating strategies may be quite disparate.

Alleles

The interdependence of mating structure and inbreeding depression.

The level of inbreeding depression depends on the genetic structure and composition of a population, and is not a meaningful concept in its own right. Models are presented for the dynamics of alleles governing mating strategy when viability is determined by generalized heterosis or lethal recessive alleles. It is shown that a protected polymorphism for mating strategy may ensue from generalized heterosis, while lethal recessive alleles may favor the common mating strategy. Further, neither model provides the conditions allowing spread of an allele when rare (protection) which are obtained by assuming as constant the level of inbreeding depression associated with the equilibrium genetic structure dictated by the common mating strategy.

Animals

Dimension reduction projection and our perception of evolution.

The evolution of a species can be viewed as a trajectory in multidimensional space. What we perceive is only a low dimensional projection from the total dimensionality necessary to fully describe a species. Motivated by the phenomenon of punctuated equilibria, it is shown that there are projections of gradualistic evolution which will have a punctuated character. However, whether our eyes and minds would choose such a projection of the total phenotype is not resolved.

Animals

The effect of variable environments on polymorphism at loci with several alleles II. Submultiplicative viabilities.

Circumstances assuring a unique stable equilibrium are investigated for a subdivided population with several alleles segregating at a single locus. For a broad class of selection regimes entailing heterozygote viabilities greater than the geometric mean of the corresponding homozygote viabilities, a stable fixation state precludes any other stable equilibria if either total-panmixia or temporal variation is operating. This extends known results for two alleles at a single locus and partially delimits when some of the bizarre behaviour engendered by multiple alleles may occur.

Alleles

Allele multiplicity in simple Mendelian disorders.

A model of selection involving two selectively equivalent classes of alleles at a locus is considered. One class consists of normal alleles A1, A2, A3,. . .; the other class consists of detrimental alleles a1, a2, a3, . . . . Mutation within and between allelic classes can occur without restriction, but selection operates in such a way as to maintain an approximately constant overall frequency of A-type and a-type alleles is derived, and it is shown that the distribution of allele frequencies in a sample of detrimental alleles depends on the forward (A to a) mutation rate but not on the selection coefficient, degree of dominance, or mutation rate among a-type alleles. Recurrent mutation therefore generates allelic multiplicity among detrimental alleles, and this is discussed in the context of clinical heterogeneity in simple Mendelian disorders.

Alleles