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Biomedical subjects

E A Murphy

Publications and source records attributed to E A Murphy.

At least 19 recordsLinked to original sources
PubMed1992

Twin studies of Alzheimer disease: II. Some predictions under a genetic model.

The twin method for investigating genetic and environmental causes of disease has been applied mostly in early-onset illnesses. Analysis of late-onset disorders requires reexamination of common assumptions about the relation between genetic causes and the degree of concordance expected. This paper considers Alzheimer disease (AD) as an example of a late-onset disorder with putative genetic factors. For argument it employs the strong hypothesis that AD is an autosomal dominant trait with age-dependent expression, as described by a previously published parametric model. That model encompasses 2 principal variants of disease: a rare form with onset in middle life, and a more common late-onset type which is nonetheless eventually fully penetrant. The present work then specifies the probability that, when a given member of a twin pair (the proband) is affected, an identical or fraternal co-twin also shows the disease. Such probability is expressed as a function of the age at onset of the proband and the current age of the pair. Even under strong working assumptions regarding genetic influence, the expected proportion of identical co-twins actually affected with AD will not exceed 40% until the subjects are about 80 years old. Therefore, except in very old subjects, modest twin concordance is a feeble argument against genetic causes, or in favor of exclusively environmental ones. In this sense the interpretation of results of twin studies in AD and other late-onset disorders differs substantially from studies of diseases with early onset.

Age Factors↗
PubMed1992

Threshold model in the genetics of age-dependent disease in twins: I. General principles as applied to Alzheimer disease.

In the context of the etiology and pathogenesis of Alzheimer disease (AD), we discuss assumptions under which categorical data on the phenotypes of twin pairs may be used to estimate standardized characteristics (correlation and the critical threshold) for an age-dependent multinomial process. Important topics include Erlangian, gamma, and Poisson processes, tetrachoric and trichoric functions, and degrees of freedom and how they relate to estimation from both an abstract and a practical standpoint. Under plausible assumptions about the age-dependence of a heritable trait, it is possible to generate sufficient degrees of freedom to test the genetic model and to explore age-dependence and the impact of environmental factors that may influence it systematically. Though general in scope, the model is focused on data from twin pairs. The statistical strategy is briefly outlined, but its properties are not examined in detail.

Aging↗
PubMed1992

Reassessment of lead exposure in New Jersey using GIS technology.

In order to prevent children's exposure to lead, a variety of sources must be controlled. The New Jersey Department of Environmental Protection and Energy (NJDEPE) is using its Geographic Information System to identify areas within Newark, East Orange, and Irvington, New Jersey, where there may be greater environmental exposure to lead. Sensitive populations are identified through the U.S. Bureau of the Census information. Blood screening data provided by the New Jersey Department of Health (NJDOH) provide reported patterns of elevated blood lead in the study area. Comparisons of these spatial patterns will assist the NJDEPE in its soil sampling activities and lead exposure research, will provide information for public education, and will provide valuable information on sections of the study area where further screening and public education may be needed.

Air Pollutants↗
PubMed1979

Finite sample properties of maximum likelihood estimates of the recombination fraction in double backcross matings in man.

The properties of the maximum likelihood estimator (MLE) of the recombination fraction, theta, based on various numbers and sizes of sibships derived from double backcross matings are exactly explored where the coupling phases are presumed equally likely (which for two-generation data is generally the case). The results indicate that for large values of theta the expectations are severely biased. The bias, variance, and measures of normality of the MLE behave erratically for small sizes and numbers of sibships. The implications for chromosome mapping are discussed.

Consanguinity↗
PubMed1979

Segregation of noisy Mendelian traits and the effect of age-dependence: a prolegomenon.

A discussion of the primordial confusion between the multiplicative Galtonian ("lognormal") trait and the imperfectly segregating Mendelian trait is laid out from a probabilistic standpoint. Several criteria used in comparing them (bimodality; bitangentiality; goodness of fit to the multinomialized form of the distribution; cumulants of the distributions) are reviewed and the inadequacy of their probabilistic properties discussed in some detail. The logical asymmetry of the normalized score ("Roberts" correction") and hence its invalidity as a criterion for distinguishing between the models is pointed out. The form of a mixture of two Gaussian distributions with fixed and equal variances but with differing age-dependent means ("the Platt model") is explored. The epistemological implications are exhibited. As a first step to restoring symmetry, a general model is proposed of which these and other models in wide use emerge as special cases. No attempt is made to deal here with the statistical aspects of the problem.

Age Factors↗
PubMed1979

Where are we going?

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Genetic Diseases, Inborn↗
PubMed1979

Seven snobberies.

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Attitude of Health Personnel↗
PubMed1978

Systemic griseofulvin therapy of monilethrix.

After a report of clinical effectiveness, four adult patients with monilethrix were treated with griseofulvin for six months at an orally administered dose of 500 mg (microsize) per day. No objective or subjective improvement was observed.

Adolescent↗
PubMed1978

Genetic and evolutionary fitness.

The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationships, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.

Biological Evolution↗
PubMed1978

The familial component in longevity--a study of offspring of nonagenarians: III. Intrafamilial studies.

The effect of parental longevity on the length of survival of offspring has been examined according to selected demographic and environmental characteristics. The present study is based on 7,103 progeny, 20 years old or older. They were the sons and daughters of 1,766 men or women, 90 or more years old, who were alive in 1922-1930 at the time of ascertainment. The age at death of the other parent of the offspring is the basis of classification used in this analysis. A positive relationship was found between age at death of the non-proband parent and the age at death of the offspring. This relationship existed regardless of similarities or differences in the characteristics analyzed.

Adult↗
PubMed1978

Neuronal ceroid-lipofuscinosis. Studies of granulocyte enzyme activities.

Neuronal ceroid-lipofuscinosis is characterized by pigmentary degeneration of the retina, psychomotor degeneration, epilepsy and intracellular deposition of ceroidlipofuscin. Recent reports have suggested that deficiency of peroxidase is the basic genetic defect. However, deficiency of myeloperoxidase could be demonstrated in some but not all patients; this deficiency was noted only when p-phenylenediamine (PPD) was used as hydrogen donor and could not be confirmed with guaiacol. We found that horseradish peroxidase (HR-P) oxidized PPD in the absence of added H2O2. The oxidative product of PPD showed the same absorption spectrum as the peroxidative product. The oxidation of PPD by HR-P was not inhibited by catalase or superoxide dismutase. In addition, catalase oxidized PPD in the presence of H2O2. Soluble and granular fractions obtained from human polymorphonuclear leukocytes (PMN) also oxidized PPD in the absence of H2O2. Addition of H2O2 inhibited the oxidation of PPD in some cell fractions. This inhibition could be partially eliminated by dialysis of the cell fractions. Thus, PPD is not a suitable hydrogen donor for the study of peroxidase. This may explain the variable results obtained by the previous investigators. In contrast, guaiacol did not show these undesirable characteristics. The PMN peroxidase (measured with guaiacol), catalase, beta-glucuronidase, acid and alkaline phosphatases were studied in individuals from three families with juvenile neuronal ceroid-lipofuscinosis. Family 1: an affected boy and healthy parents; all showed normal enzyme activities in both soluble and granular fractions. Family 2: two affected sisters, one healthy sib and mother, and Family 3: one affected boy; all showed reduced peroxidase activities in the granular fractions. Other enzymes were normal. The role of peroxidase deficiency in the pathogenesis of neuronal ceroid-lipofuscinosis is not clear. The basic defect of this syndrome remains uncertain.

Acid Phosphatase↗