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Biomedical subjects

M J Wade

Publications and source records attributed to M J Wade.

At least 19 recordsLinked to original sources
PubMed1992

Predicting blood lead concentrations from environmental concentrations.

A method is presented by which blood lead concentrations can be estimated from environmental concentrations using a multipathway analysis. For the ingestion and dermal uptake pathways the incremental increase in blood lead concentration is estimated as the product of the concentration in the relevant medium, a medium-specific contact rate, and an empirically determined ratio between intake and blood level. The inhalation pathway omits the contact rate and uses a ratio between the concentration in blood and the concentration in air. Model outputs corresponding to various input parameters are presented, and some of these are compared with outputs from the U.S. Environmental Protection Agency's Lead Biokinetic/Uptake model, Lead 5.

Adult↗
PubMed1992

On the carcinogenicity of cadmium by the oral route.

Cadmium and cadmium compounds are carcinogenic both by inhalation and by injection. For purposes of risk assessment, a prudent public health approach has been that, if a chemical has been demonstrated to be carcinogenic by one route, it should be considered carcinogenic by all routes. This policy has been questioned for several toxic metals including cadmium. After reviewing the literature on cadmium carcinogenicity and genotoxicity, we think that cadmium should be considered noncarcinogenic by the oral route. The bases for this decision included: (1) a database for genotoxicity of cadmium with more negative test results than positive results and with most positive results in in vitro tests, indicating that cadmium has limited genotoxicity; (2) some epidemiologic evidence of respiratory tract cancer and prostatic cancer in people occupationally exposed to airborne cadmium but no reliable evidence of gastrointestinal tract cancers in workers; and (3) a large dietary oncogenicity study in rats of cadmium chloride at several dose levels, including a maximally tolerated dose (50 ppm) in males, which showed no increase of tumors due to cadmium ingestion in all of the 19 tissues examined. The conclusion that an agent, which has been shown to be carcinogenic by one route of exposure, is not carcinogenic by a second route should be made only in the presence of robust data which indicate the lack of effect via the second route of exposure.

Administration, Oral↗
PubMed1991

"Runaway" social evolution: reinforcing selection for inbreeding and altruism.

Kin selection theory predicts that altruistic behaviors, those that decrease the fitness of the individual performing the behavior but increase the fitness of the recipient, can increase in frequency if the individuals interacting are closely related. Several studies have shown that inbreeding therefore generally increases the effectiveness of kin selection when fitnesses are linear, additive functions of the number of altruists in the family, although with extreme forms of altruism, inbreeding can actually retard the evolution of altruism. These models assume that a constant proportion of the population mates at random and a constant proportion practices some form of inbreeding. In order to investigate the effect of inbreeding on the evolution of altruistic behavior when the mating structure is allowed to evolve, we examined a two-locus model by computer simulation of a diploid case and illustrated the important qualitative features by mathematical analysis of a haploid case. One locus determines an individual's propensity to perform altruistic social behavior and the second locus determines the probability that an individual will mate within its sibship. We assumed positive selection for altruism and no direct selection at the inbreeding locus. We observed that the altruistic allele and the inbreeding allele become positively associated, even when the initial conditions of the model assume independence between these loci. This linkage disequilibrium becomes established, because the altruistic allele increases more rapidly in the inbreeding segment of the population. This association subsequently results in indirect selection on the inbreeding locus. However, the dynamics of this model go beyond a simple "hitch-hiking" effect, because high levels of altruism lead to increased inbreeding, and high degrees of inbreeding accelerate the rate of change of the altruistic allele in the entire population. Thus, the dynamics of this model are similar to those of "runaway" sexual selection, with gene frequency change at the two loci interactively causing rapid evolutionary change.

Alleles↗
PubMed1991

Wright's shifting balance theory: an experimental study.

Experimental confirmation of Wright's shifting balance theory of evolution, one of the most comprehensive theories of adaptive evolution, is presented. The theory is regarded by many as a cornerstone of modern evolutionary thought, but there has been little direct empirical evidence supporting it. Some of its underlying assumptions are viewed as contradictory, and the existence and efficacy of the theory's fundamental adaptive process, interdemic selection, is the focus of controversy. Interdemic selection was imposed on large arrays of laboratory populations of the flour beetle Tribolium castaneum in the manner described by Wright: the differential dispersion of individuals from demes of high fitness into demes of low fitness. A significant increase in average fitness was observed in the experimental arrays when compared to control populations with equivalent but random migration rates. The response was not proportional to the selection differential: The largest response occurred with interdemic selection every two generations rather than every generation or every three generations. The results indicate that the interdemic phase of Wright's shifting balance theory can increase average fitness and suggest that gene interactions are involved in the observed response.

Adaptation, Physiological↗
PubMed1990

Female copying increases the variance in male mating success.

Theoretical models of sexual selection assume that females choose males independently of the actions and choice of other individual females. Variance in male mating success in promiscuous species is thus interpreted as a result of phenotypic differences among males which females perceive and to which they respond. Here we show that, if some females copy the behavior of other females in choosing mates, the variance in male mating success and therefore the opportunity for sexual selection is greatly increased. Copying behavior is most likely in non-resource-based harem and lek mating systems but may occur in polygynous, territorial systems as well. It can be shown that copying behavior by females is an adaptive alternative to random choice whenever there is a cost to mate choice. We develop a statistical means of estimating the degree of female copying in natural populations where it occurs.

Animals↗
PubMed1990

Cytoplasmically inherited reproductive incompatibility in Tribolium flour beetles: the rate of spread and effect on population size.

This paper reports on the effects of a cytoplasmically inherited reproductive incompatibility in different genetic strains of the flour beetle, Tribolium confusum. We measured the rate of spread and the effect of host population size using different initial frequencies of infection with a cytoplasmic factor that mediates reproductive incompatibility. There were two experiments, in one the infected and uninfected lines were from the same genetic strain, b-Yugoslavia. In the other, the infected line was from the "high cannibalism" bIV strain and the uninfected line from the "low cannibalism" bI strain. We estimate that the fitness ratio of infected to uninfected in b-Yugoslavia is 0.63 and the observed rate of spread for this strain corresponds to a model of cytoplasmic inheritance that takes into account the productivity differences between the infected and cured lines. In the bI-bIV experiment, because the uninfected and infected lines are from different genetic strains, we cannot partition the effects of the cytoplasmic factor from other factors. The rate of spread in the bI-bIV experiment is faster in males and slower in females than predicted from a model of cytoplasmic inheritance. In both experiments, productivity varies with initial infection frequency; however, the relationship is not explained by a simple model that predicts lower population size at intermediate infection frequencies.

Animals↗
PubMed1987

Dominant lethal study of ribavirin in male rats.

Ribavirin, a new synthetic antiviral agent, was studied for dominant lethal effects in male CD rats. The drug was administered intraperitoneally at doses of 50, 100 and 200 mg/kg/day for 5 days. Males were mated weekly with 8 consecutive batches of female rats. Marginal increase in early foetal death detected in Assessment Weeks 3 and 8 in females mated with the low-dose and high-dose males were not dose-related and were most probably chance events caused by the particularly low vehicle control frequencies for these 2 weeks. Also, the slightly reduced pregnancy proportion among females mated with the high-dose treated males was to a substantial extent the effect of a single male rate which failed to fertilize any females. Ribavirin was, therefore, regarded as being devoid of any mutagenic potential demonstrable by a rat dominant lethal assay.

Animals↗
PubMed1986

The incidence of epilepsy after ventricular shunting procedures.

One hundred eighty of 207 consecutive patients with ventricular shunts were studied to determine the incidence of post-shunt epilepsy. Of these 17 (9.4%) developed seizures. The incidence fell from 15.2% in children younger than 1 year to 6.9% in patients over 50 years of age, but age was not statistically significant. Of patients with a parietal ventricular catheterization site only 6.6% had convulsions, in contrast to 54.5% of those with a frontal locus. The incidence of seizures rose with multiple ventricular catheter revisions, but was unrelated to bilaterality of shunting. The risk of seizures fell from 5% in the 1st year after shunting to 1.1% after the 3rd year.

Adolescent↗
PubMed1985

Microorganism mediated reproductive isolation in flour beetles (genus Tribolium).

Reproductive isolation is induced by microorganisms in diverse geographic strains of the flour beetle Tribolium confusum (Coleoptera:Tenebrionidae). The incompatibility between populations is due to nongenetic cytoplasmically inherited factors. Males of infected strains produce no progeny when crossed with females of noninfected strains; however, they produce "normal" numbers of progeny when crossed with infected females. Males from noninfected strains show no reproductive isolation. Infected strains of T. confusum can be cured when tetracycline or other antibiotics are added to the flour medium. "Cured" strains become partially reproductively isolated from all noncured strains including the source strain

Animals↗
PubMed1985

The influence of multiple inseminations and multiple foundresses on social evolution.

The breeding biology of a population determines the way in which individuals are distributed within and between progeny groups and, thus, affects the genetic variation within and between these groups. The breeding biology of any organism can be characterized by the distribution of the numbers of mates of females, the apportionment of paternity among males, the distribution of the numbers of females reproducing in common nests, and the apportionment of total fecundity within a nest among founding females. In addition, the possibility of genetic correlations among mates or among founding females is an important consideration and will be addressed in a later paper. The influence of the breeding biology on social evolution was evaluated by deriving the necessary conditions for the spread of genes for social behaviors and the rate of spread of these genes for populations with different breeding biologies. The first step in this derivation is to demonstrate that selection for genes determining social behavior can be represented as the covariance between gene frequency and relative fitness. Secondly, it is shown that this covariance can be formally partitioned into within and between group components. Thirdly, each covariance component is shown to be equivalent to the product of a genetic variance and a coefficient of linear regression of relative fitness on gene frequency. Lastly, specific models for the genotype fitnesses and breeding biologies are assumed and the necessary conditions for the increase in the frequency of altruistic alleles are obtained. The theory illustrates that variation in the numbers of mates per female has less of an effect on the evolution of social behaviors than does variation in the numbers of reproductive females per nest. In addition, it points out that the harmonic mean number of mates per female or of females per nest is a more useful summary statistic for characterizing populations with respect to the expected degree of evolved sociality than is the arithmetic mean.

Alleles↗
PubMed1979

Mutagenic action of a series of epoxides.

The mutagenicity of a series of 13 epoxide compounds was studied using a bacterial plate assay system. The histidine-dependent tester strains TA98 (for frameshift mutagens) and TA100 (for base-pair substitution mutagens) of Salmonella typhimurium were used. Mutagenicity was evaluated both with and without the additon of rat liver microsomal extract. Dieldrin, diglycidyl ether of bis phenol A and 3 of its homologues were not mutagenic. Allyl glycidyl ether, n-butyl glycidyl ether, vinly cyclohexene diepoxide, glycidol, glycidal-dehyde, diglycidyl ether, diepoxybutane and diglycidyl ether of substituted glycerine were mutagenic in the TA100 strain, causing reversion of the bacteria to histidine independence. Dose-reponse curves of the mutagenicity of the latter 4 compounds were obtained. On a molar basis, glycidaldehyde was about 20-50 times more potent in producing mutation that were the other 3 epoxides in the dose-response test. In general, the mutagenicity of the epoxides was not enhanced or diminished by the addition of microsomal extract.

Drug Evaluation, Preclinical↗
PubMed1978

Device for quantitative cytochemistry: a computerized scanning microdensitometer 'grain counter'.

A computerized scanning microdensitometer and autoradiographic grain counter was able to provide quantitative data on the cytochemical final reaction product formed within a single cell and also quantitate the kinetics of its formation. Optical density and area measurements were performed on hundreds of leukocytes from slides previously stained to demonstrate any one of a variety of reactions. These included cellular glycogen, lipids, peroxidase, esterases, alkaline phosphatase, and acid phosphatase. In addition to these slide studies, chamber studies with an adapted Dvorak-Stotler Chamber allowed the measurement of enzyme kinetics within single cells.

Autoradiography↗
PubMed1976

Group selections among laboratory populations of Tribolium.

Selection at the population level or group selection is defined as genetic change that is brought about or maintained by the differential extinction and/or proliferation of populations. Group selection for both increased and decreased adult population size was carried out among laboratory populations of Tribolium castaneum at 37-day intervals. The effect of individual selection within populations on adult population size was evaluated in an additional control series of populations. The response in the group selection treatments occurred rapidly, within three or four generations, and was large in magnitude, at times differing from the controls by over 200%. This response to selection at the populational level occurred despite strong individual selection which caused a decline in the mean size of the control populations from over 200 adults to near 50 adults in nine 37-day intervals. "Assay" experiments indicated that selective changes in fecundity, developmental time, body weight, and cannibalism rates were responsible in part for the observed treatment differences in adult population size. These findings have implications in terms of speciation in organisms whose range is composed of many partially isolated local populations.

Animals↗