PubMed Health⌕ Search

Biomedical subjects

M Conrad

Publications and source records attributed to M Conrad.

At least 55 records · Page 3Linked to original sources
PubMed1986

Induction of deletion and insertion mutations by 9-aminoacridine. An in vitro model.

The ability of 9-aminoacridine to induce mutagenic lesions during DNA replication in vitro was investigated. The ampicillinase gene of pBR322 was replicated in vitro in the presence of 9-aminoacridine. Transfection of the replicated DNA into Escherichia coli gave Amps mutants. Determination of the base changes in 76 of these mutants indicated that the spectrum of mutations induced by 9-aminoacridine was consistent with its action in vivo. Both large (407-base) and small (1- and 2-base) deletions were induced at repetitive sequences. The frequency of deletion mutations depended on the identity of the base deleted and sequences surrounding the deletions. The characteristics of the frameshift mutations induced were consistent with the interactions of 9-aminoacridine with DNA. These results establish that 9-aminoacridine can induce frameshift mutations during the replication process and provide an in vitro model of frameshift induction for mechanistic studies.

Aminacrine↗
PubMed1986

O6-methylguanine mutation and repair is nonuniform. Selection for DNA most interactive with O6-methylguanine.

Mutations were induced in the ampicillinase gene of a bacteriophage f1/pBR322 chimera both by incorporation of O6-methyl-dGTP opposite T during DNA replication in vitro and by site-directed mutagenesis using O6-methylguanine-containing oligonucleotides. After passage of the DNA through Escherichia coli, analysis of 151 O6-methyl-dGTP-induced mutations indicated a significantly greater number of unmutated mutation sites than expected, whereas the mutated sites generally fit a Poisson distribution. The unmutated sites are assumed to be caused by the inability of some sequences to tolerate the presence of a tetrahedral methyl group within the confines of a Watson-Crick helix (Toorchen, D., and Topal, M.D. (1983) Carcinogenesis 4, 1591-1597). A consensus of the DNA sequences surrounding unmutated mutation sites was derived. The consensus sequence had significant similarity to the region of the rat Harvey ras oncogene containing the N-methyl-N-nitrosourea activated site for transformation (Zarbl, H., Sukumar, S., Arthur, A. V., Dionisio, M.-Z., and Barbacid, M. (1985) Nature 315, 382-385). We propose that direct alkylation at O6 of a guanine present within the consensus sequence may produce a DNA conformation less subject to repair. Mutation by O6-methylguanine-containing oligonucleotides demonstrated that repair of the O6-methylguanine lesions varied at least 3-4-fold with position of the lesion.

Alkylation↗
PubMed1986

DNA structural variability as a factor in gene expression and evolution.

Redundant DNA can buffer sequence dependent structural deviations from an ideal double helix. Buffering serves a mechanistic function by reducing extraneous conformational effects which could interfere with readout or which would impose energetic constraints on evolution. It also serves an evolutionary function by allowing for gradual variations in conformation-dependent regulation of gene expression. Such gradualism is critical for the rate of evolution. The buffer structure concept provides a new interpretation for repetitive DNA and for exons and introns.

Base Sequence↗
PubMed1985

Neuron generator potentials evoked by intracellular injection of cyclic nucleotides and mechanical distension.

Depolarization of neuron membrane was shown to occur during cAMP injection by means of both iontophoresis and pressure. Distension of the neuron by means of blowing with large volumes of solution without cAMP can produce reversible responses. The time course can be made similar to that of the cAMP effect and the responses can be repeated many times in the same neuron. The effect of cAMP can be differentiated from the mechanical response by injecting small volumes of concentrated solutions. The delay in this depolarization response to cAMP is only 0.1-0.3 s. The calculated time of diffusion from the electrode tip to the membrane is about 10 times greater. The similarity of cAMP and mechanical responses and the short delay of the cAMP effect suggests that a cAMP effect may be mediated by mechanical signals in the cytoskeleton.

Animals↗
PubMed1985

Evolve III: a discrete events model of an evolutionary ecosystem.

Evolve III is a discrete events model of an evolutionary ecosystem. The model includes three levels of organization: population, organism and genetic structure. Each of these components was modeled independently, so that selective replacement of subsystems can be used to create families of models capable of testing alternative hypotheses about the real system. To demonstrate the use of the model we describe an experiment on the relationship between adaptability of populations and the variability of the environment. Populations cultured in a constant environment usually dominated those cultured in a variable environment when both were placed in a variable environment at an early stage of development, whereas the opposite is the case at later stages of development. This agrees with experiments on laboratory microcosms and lends credence to the potential predictive value of the model.

Biological Evolution↗
PubMed1985

Evolve II: a computer model of an evolving ecosystem.

The Evolve II program is a model of an ecosystem in which organisms are allowed to evolve. Organisms are subject to a changeable environment and competition from other organisms for a limited food supply. The gene structure may change through mutation. A feature of Evolve II is that the magnitude of phenotypic change resulting from mutation is itself a property of the gene. The system was studied under a number of environmental variation schemes. We report three significant findings. Two species (lineages with distinctly different survival strategies) evolved and coexisted in the same environmental conditions. Organisms developed a resistance to phenotypic change in response to mutation in slowly varying environments. However, traits which favor survival of the individual at the expense of reproduction could in some cases undergo phenotypic change in response to mutation despite the fact that this did not favor the survival of the offspring. This demonstrates that gene structures can evolve which are advantageous from the standpoint of the lineage, but not advantageous from the standpoint of individual offspring.

Aging↗
PubMed1984

Effects of captopril on pulmonary haemodynamics.

The effects of oral captopril on pulmonary haemodynamics were studied in two groups of 6 patients, one of subjects with chronic respiratory failure (PaO2 52 +/- 5.1 mmHg, PaCO2 54 +/- 2.1 mmHg), and the others with chronic heart failure and high plasma renin activity. Two potential mechanisms of its actions were assessed, namely inhibition of hypoxic vasoconstriction and inhibition of the possible effects of angiotensin II on the pulmonary circulation. There were significant (p less than 0.05) decreases in mean arterial pressure, pulmonary wedge pressure and in systemic arterial resistance associated with improvement in cardiac index in both groups. In the chronic respiratory failure group there was no change in blood gases, mean pulmonary arterial pressure or pulmonary vascular resistance. An increase in driving pressure (p less than 0.05) indicated that captopril had had no effect on pulmonary haemodynamics. In chronic heart failure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure were decreased by a similar extent, so that driving pressure and pulmonary vascular resistance were not changed. It is concluded that oral captopril did not inhibit hypoxic vasoconstriction, and that it modified pulmonary haemodynamics in chronic heart failure patients with high renin activity only as a consequence of reduction in systemic afterload.

Adult↗
PubMed1983

Evidence that natural selection acts on silent mutation.

Analysis of nucleic acid sequence data of mammalian hemoglobin, yeast cytochrome c, and human interferon reveals strong biases in favor of specific codons. These biases do not appear to dissipate over time, suggesting that an indirect form of selection acts on silent mutations. The data are compatible with the "bootstrapping" hypothesis that silent mutations which alter the rate of evolution can hitchhike with traits whose appearance they facilitate. Selection involving modulating effects of codon usage on gene expression may also be involved, but the data appear to exclude simple maximization of gene expression.

Animals↗
PubMed1983

[Chronic obstructive bronchopneumopathies as manifestations of a Gougerot-Sjögren syndrome. Apropos of 2 cases].

The authors report two cases of Sjögren's syndrome presenting as chronic obstructive bronchopulmonary disease. They stress the need to consider the possibility of Sjögren's syndrome when confronted with chronic obstructive lung disease in a woman in her fifties, without history of bronchopulmonary disease or smoking, unexposed to occupational dust and without ENT infection or gastro-oesophageal reflux.

Aged↗