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Biomedical subjects

A C Wilson

Publications and source records attributed to A C Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Superiority of nonpharmacologic therapy compared to propranolol and placebo in men with mild hypertension: a randomized, prospective trial.

We compared the effects of nonpharmacologic therapy, propranolol monotherapy, and placebo on blood pressure, metabolic, exercise, and quality of life variables in a 12-week, randomized, placebo-controlled trial of 79 male patients with hypertension. A significant reduction in diastolic blood pressure was observed with both nondrug therapy (-8.0 +/- 1.08 mm Hg) and propranolol (-9.5 +/- 1.46 mm Hg) compared to placebo (-0.1 +/- 2.01 mm Hg). However, only patients receiving nonpharmacologic therapy showed a reduced body mass index, lower total and low-density lipoprotein serum cholesterol levels, and increased exercise tolerance compared to both propranolol and placebo. Patients receiving propranolol felt less anxious and unsure but showed a significant decrement in nocturnal penile tumescence compared to both placebo and nondrug therapy. Patients receiving nondrug therapy felt more energetic and reported improved sexual arousal and greater sexual satisfaction after treatment. Reductions in blood pressure in the nondrug treatment group were related to both weight reduction and improved fitness. We conclude that nondrug therapy is effective in controlling blood pressure in men with mild hypertension and is associated with improvements in weight, lipoprotein levels, and exercise tolerance compared to both propranolol and placebo. Quality of life assessments further support the use of nondrug therapy in this context.

Diet, Reducing↗
PubMed1992

Evolutionary genetics of ruminant lysozymes.

Comparative studies of mammalian lysozymes and their genes have contributed to knowledge of how new functions arise during evolution. The recruitment of lysozymes for functioning in the stomach fluid of ruminants has occurred in response to selection pressures that are partly known and on a time-scale that is known. A semiquantitative analysis of adaptive evolution is thus made possible by the ruminant lysozyme system. Large-scale production of lysozyme by the stomach lining entailed gene duplication as well as a change in gene expression. Remoulding of the lysozyme for working and lasting in the stomach fluid involved accelerated amino acid replacements, which may have been facilitated by intergenic recombination. The possibility that multigene families can accelerate adaptive evolution, by virtue of their capacity for bringing together functionally coupled substitutions, receives emphasis in this review.

Adaptation, Physiological↗
PubMed1992

Body fat and overweight among children and adolescents with diabetes mellitus.

Body composition was assessed in 68 children and adolescents with diabetes mellitus. Body fat was measured by skinfold thickness and the results were compared with those obtained by bioelectrical impedance methods (r = 0.76, p less than 0.001). Percentage body fat from skinfold thickness estimations was 12-38%. Girls appeared to be most at risk of obesity during puberty with mean body fat 31%, significantly greater than in prepubertal girls (22%, p = 0.001) and pubertal boys (21%, p less than 0.001). Body fat increased progressively through puberty in girls, with those in late puberty (stages 4 and 5) having significantly more percentage body fat than those in earlier puberty (stages 2 and 3, p less than 0.001). Those in late puberty also received significantly more insulin per kilogram body weight (p = 0.05) and had higher HbA1 levels (p less than 0.05) than prepubertal girls.

Adipose Tissue↗
PubMed1992

The prognostic significance of very low frequency ventricular ectopic activity in survivors of acute myocardial infarction. BHAT Study Group.

Survivors of myocardial infarction with less than 2 PVC/h on 24-h ambulatory electrocardiography were followed up for an average of 25 months (11 to 40 months) while receiving a placebo (1,222 patients) or propranolol, 180 or 240 mg/day (1,234 patients). Three quarters of the participants with PVCs had an average of less than 2 PVC/h. Only 16 percent did not have any ventricular ectopic activity during the 24 h. Analysis of total mortality according to the number of premature ventricular complexes per hour showed that patients who had PVCs with a very low frequency (less than 0.5/h) had 49 percent higher mortality than patients who did not have any PVC. Patients who had greater than 0.5 PVC/h but less than 1 PVC/h had a statistically significant higher mortality rate, 11.7 vs 4.1 percent (p less than 0.0001) than patients who had no PVC. These data indicate that low ventricular ectopic activity frequency is associated with increased mortality in survivors of acute myocardial infarction.

Cardiac Complexes, Premature↗
PubMed1991

African populations and the evolution of human mitochondrial DNA.

The proposal that all mitochondrial DNA (mtDNA) types in contemporary humans stem from a common ancestor present in an African population some 200,000 years ago has attracted much attention. To study this proposal further, two hypervariable segments of mtDNA were sequenced from 189 people of diverse geographic origin, including 121 native Africans. Geographic specificity was observed in that identical mtDNA types are shared within but not between populations. A tree relating these mtDNA sequences to one another and to a chimpanzee sequence has many deep branches leading exclusively to African mtDNAs. An African origin for human mtDNA is supported by two statistical tests. With the use of the chimpanzee and human sequences to calibrate the rate of mtDNA evolution, the age of the common human mtDNA ancestor is placed between 166,000 and 249,000 years. These results thus support and extend the African origin hypothesis of human mtDNA evolution.

Africa↗
PubMed1991

Paternal inheritance of mitochondrial DNA in mice.

For nearly 20 years it has been assumed on the basis of low-resolution experiments that mitochondrial (mt)DNA, in contrast to the genes in the nucleus, has an exclusively maternal mode of inheritance in animals. Using the polymerase chain reaction, paternally inherited mtDNA molecules have now been detected in mice at a frequency of 10(-4), relative to the maternal contributions. These mice were hybrids between two inbred strains (C57BL/6J and Mus spretus) whose mtDNAs can be distinguished easily. This new mode of inheritance provides a mechanism for generating heteroplasmy and may explain mitochondrial disorders exhibiting biparental transmission.

Animals↗
PubMed1991

Branching pattern in the evolutionary tree for human mitochondrial DNA.

Eighty-eight types of mitochondrial (mt) DNA were found by sequencing the most variable part of the control region from 117 Caucasians. In the tree relating those types, most of the branching events occur about two-thirds of the way from the root of the tree to the tips of the branches. Moreover, the distribution of sequence differences between all possible pairs of individuals is approximately Poisson. Other non-African populations show a similar pattern. Assuming a neutral model, these findings imply that the probability of survival of new lineages has undergone dramatic changes, probably due to population expansion. Conversely, African populations show multimodal distributions fitting with a model of constant population size.

Animals↗
PubMed1991

Mitochondrial resolution of a deep branch in the genealogical tree for perching birds.

Animal mitochondrial DNA (mtDNA) is known to contain information about the genealogical relations among closely related species and is shown here to yield information about distant relations as well. Our results also draw attention to the need for caution in using third positions of codons for tree construction. This is evident from comparative studies of the cytochrome b gene in 13 species representing major groups within the order of perching birds (Passeriformes). Sequences of a 924 base-pair segment of this gene were obtained from each of these species via the polymerase chain reaction and a novel set of versatile primers. With a woodpecker sequence as an outgroup, trees that separate songbirds from other perching birds and resolve the ancient branch leading to songbirds were obtained utilizing the conservative first and second positions of codons. Analysis of positions within codons suggests that, for deep branches, the skewed base composition at the fast-changing third positions can result in phylogenetic disinformation, which conflicts with the information retained in the first and second positions. The mitochondrial tree shows broad concordance with that based on hybridization of nuclear DNA; however, parsimony and maximum likelihood methods suggest a close kinship between thrushes and Australian babblers, in agreement with the traditional morphological classification.

Amino Acid Sequence↗
PubMed1991

Stomach lysozyme gene of the langur monkey: tests for convergence and positive selection.

Genomic blotting and enzymatic amplification show that the genome of the langur monkey (like that of other primates) contains only a single gene for lysozyme c, in contrast to another group of foregut fermenters, the ruminants, which have a multigene family encoding this protein. Therefore, the langur stomach lysozyme gene has probably evolved recently (i.e., within the period of monkey evolution) from a conventional primate lysozyme. The sequences of cDNAs for the stomach lysozyme of langur and the conventional lysozymes of three other Old World monkeys were determined. Identification of the promoter for the stomach gene and comparison to the human gene, which is expressed conventionally in macrophages, show that both lysozyme genes use the same promoter. This suggests that the difference in expression patterns is due to change(s) in enhancer or silencer regulatory elements. With the cDNA sequences the hypothesis that the langur stomach lysozyme has converged in amino acid sequence upon the stomach lysozymes of ruminants is tested. Consistent with the convergence hypothesis, only those sites that specify amino acids in the mature lysozyme are shared uniquely with ruminant lysozyme genes. None of the silent sites at third positions of codons or in noncoding regions support a link between the langur and ruminants. Statistical analysis based on silent sites rules out the possibility of horizontal transfer of a stomach lysozyme gene between the langur and ruminant lineages and supports the close relationship of the langur lysozyme gene to that of other monkeys.

Animals↗
PubMed1991

Rearrangements of mitochondrial transfer RNA genes in marsupials.

The nucleotide sequences of the mitochondrial origin of light-strand replication and the five tRNA genes surrounding it were determined for three marsupials. The region was found to be rearranged, leaving only the tRNA(Tyr) gene at the same position as in placental mammals and Xenopus. Distribution of the same rearranged genotype among two marsupial families indicates that the events causing the rearrangements took place in an early marsupial ancestor. The putative mitochondrial light-strand origin of replication in marsupials contains a hairpin structure similar to other vertebrate origins and; in addition, extensive flanking sequences that are not found in other vertebrates. Sequence comparisons among the marsupials as well as placentals indicate that the tRNA(Tyr) gene has been evolving under more constraints than the other tRNA genes.

Animals↗
PubMed1991

Evolution of the cytochrome b gene of mammals.

With the polymerase chain reaction (PCR) and versatile primers that amplify the whole cytochrome b gene (approximately 1140 bp), we obtained 17 complete gene sequences representing three orders of hoofed mammals (ungulates) and dolphins (cetaceans). The fossil record of some ungulate lineages allowed estimation of the evolutionary rates for various components of the cytochrome b DNA and amino acid sequences. The relative rates of substitution at first, second, and third positions within codons are in the ratio 10 to 1 to at least 33. For deep divergences (greater than 5 million years) it appears that both replacements and silent transversions in this mitochondrial gene can be used for phylogenetic inference. Phylogenetic findings include the association of (1) cetaceans, artiodactyls, and perissodactyls to the exclusion of elephants and humans, (2) pronghorn and fallow deer to the exclusion of bovids (i.e., cow, sheep, and goat), (3) sheep and goat to the exclusion of other pecorans (i.e., cow, giraffe, deer, and pronghorn), and (4) advanced ruminants to the exclusion of the chevrotain and other artiodactyls. Comparisons of these cytochrome b sequences support current structure-function models for this membrane-spanning protein. That part of the outer surface which includes the Qo redox center is more constrained than the remainder of the molecule, namely, the transmembrane segments and the surface that protrudes into the mitochondrial matrix. Many of the amino acid replacements within the transmembrane segments are exchanges between hydrophobic residues (especially leucine, isoleucine, and valine). Replacement changes at first and second positions of codons approximate a negative binomial distribution, similar to other protein-coding sequences. At four-fold degenerate positions of codons, the nucleotide substitutions approximate a Poisson distribution, implying that the underlying mutational spectrum is random with respect to position.

Amino Acid Sequence↗
PubMed1991

Genetic analysis of a switch in cell specificity of P lysozyme expression in molossinus mice.

An electrophoretic survey of concentrations of lysozymes M and P was carried out with seven species in the house mouse group (spretus, hortulanus, abbotti, musculus, castaneus, domesticus and molossinus). In most species M is the predominant lysozyme in all tissues tested, except the small intestine, where P predominates if present. In inbred strains of molossinus mice P is more abundant than M in all tissues tested. The phenotypes of high expression of P lysozyme and low expression of M lysozyme in peritoneal and alveolar macrophages were examined genetically. Results of interspecific crosses and backcrosses to domesticus mice support the model that the phenotypes are caused by mutation(s) tightly linked to the lysozyme locus. Alleles at the regulatory loci show additive inheritance.

Animals↗
PubMed1991

Mode and tempo of molecular evolution in the nematode caenorhabditis: cytochrome oxidase II and calmodulin sequences.

Through direct sequencing methods, the mitochondrial gene for cytochrome oxidase subunit two (CO II) and the single-copy nuclear gene for calmodulin were compared among strains of Caenorhabidits elegans and two other Caenorhabditis species (C. remanei and C. briggsae). In addition the CO II sequence was determined from a distantly related nematode, Steinernema intermedii. Among the 11 strains of C. elegans tested, there are four types of CO II gene, arising from two major lineages. Levels of intraspecific difference in the CO II gene are low (less than 2.0%) compared to the extraordinary divergence between congeneric species, which is about 50% when corrected for multiple hits. Concordant with the increase in divergence between taxa is a change in the pattern of substitution from a strong transition bias (24 transitions compared to two transversions) within species to a substitution pattern that appears to reflect the base composition of the mitochondrial genome when more divergent nematodes are compared. The base composition of the Caenorhabditis CO II gene is strongly biased toward A + T at all three positions of codons and appears to constrain the amino acid composition of the protein. Both the CO II and calmodulin genes show extreme conservation of amino acid sequences. When the accumulation of changes at silent sites in the two genes is compared among strains, it becomes evident that the mitochondrial gene is changing faster than the nuclear gene.

Amino Acid Sequence↗