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Biomedical subjects

L A Cox

Publications and source records attributed to L A Cox.

At least 55 records · Page 3Linked to original sources

Head circumference standards for Irish children.

A cross-sectional study measuring head circumference was performed on 3,344 Irish Children aged from 5 to 19 years. Comparison with other countries showed a slightly larger head circumference than the 1965 British standards produced by Tanner, but significantly smaller than the Ounsted data from Oxford. There was no significant difference between the urban and rural children, but the children of non-manual workers had a significantly larger head than those of manual workers.

Adolescent↗

A longitudinal study of total and free thyroid hormones and thyroxine binding globulin during normal puberty.

Thyroid hormones are essential for normal pubertal growth, yet the changes in total and, especially, free thyroid hormones and thyroxine-binding globulin during puberty have not been adequately defined. Serum from 39 normal children (20 girls, 19 boys) between the ages of 10 and 15 years were assayed for total T4, free T4, free T3 and thyroxine-binding globulin at 6-monthly intervals; the free hormone assays were valid, non-analogue methodologies. In the girls, free T4 levels fell from 15.7 +/- 0.6 pmol/l at 10 years to 13.0 +/- 0.6 (p less than 0.001) at 12.5 years before rising to 15.9 +/- 0.7 at 15 years; this nadir occurred at puberty stages 3-4. Changes in total T4 followed a similar pattern with a slight delay in the nadir (13 years, puberty stage 4). In the boys, free T4 fell from 16.3 +/- 0.6 pmol/l at 10 years to 14.3 +/- 0.3 at 13.5 years, then rising to 15.4 +/- 0.5 at 15 years; the nadir again occurred at puberty stages 3-4. The corresponding nadir in total T4 which occurred at puberty stages 4-5 was not apparent by age analysis. Thyroxine-binding globulin concentrations remained unchanged in the girls, but fell slightly in the boys during later puberty. Free T3 concentrations in the girls showed a progressive fall after 12.5 years which was significant by the age of 14 when most had been in puberty stage 5 for more than 1 year. The boys showed no change of free T3 concentration throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Acceptable cancer risks: probabilities and beyond.

The acceptability of cancer risk requires consideration of factors that extend beyond mere numerical representations, such as either individual lifetime risk in excess of background and excess incidence. Recently, use of these numbers has been tempered by the addition of qualitative weights-of-evidence that describe the degree of support provided by animal and epidemiologic results. Nevertheless, many other factors, most of which are not quantitative, require incorporation but remain neglected by the analyst eager to use quantitative results. In this paper we show that simple risk measures are often fraught with problems. Moreover, these measures do not incorporate the very essence of acceptability, which includes notions of responsibility, accountability, equity, and procedural legitimacy, among others. We link the process of risk assessment to those legal and regulatory standards that shape it. These standards are among the principal means to resolve risk-related disputes and to enhance the balancing of competing interests when science and law meet on uncertain and often conjectural ground. We conclude the paper with a proposal for the portfolio approach to manage cancer risks and to deal with uncertain scientific information. This approach leads to the concept of "provisional acceptability," which reflects the choices available to the decisionmaker, and the trade-offs inherent to such choices.

Humans↗

The baboon gene for apolipoprotein A-I: characterization of a cDNA clone and identification of DNA polymorphisms for genetic studies of cholesterol metabolism.

We have isolated and sequenced a baboon apolipoprotein A-I (ApoA-I) clone from a liver cDNA library using a human cDNA hybridization probe. This baboon cDNA contains the entire ApoA-I coding region (801 bp, 267 aa), a 3' untranslated region, and a poly(A)tail. Among comparisons with apoAI sequences from other species, the baboon cDNA is most similar to that of the cynomolgus macaque (99.2% homologous) and least similar to the rat sequence (72.6% homologous). A high frequency of nonsynonymous substitutions are observed by alignment of baboon and human apoAI cDNAs, but comparisons of hydrophilicity profiles show that protein structure is conserved by substitutions of aa with similar properties. A polymorphic PstI cleavage site was identified by Southern blot analysis and subsequently mapped to the 5' end of the baboon apoAI gene. To identify effects of apoAI allelic variation on cholesterol metabolism, we used immunoblotting to compare the distributions of ApoA-I among lipoprotein size classes in baboons from each genotype under basal and atherogenic diets. We observed an increase of ApoA-I in high density lipoprotein (size class 1) particles after atherogenic diets in homozygotes for one allele, as compared to slight decreases in the other genotypes.

Amino Acid Sequence↗

The baboon apolipoprotein E gene: structure, expression, and linkage with the gene for apolipoprotein C-1.

To develop the baboon model for molecular genetic studies of atherosclerosis, we have cloned and sequenced the baboon apolipoprotein E (apo E) gene. The baboon apo E gene encodes the E4 isoform with respect to specific amino acid positions, suggesting that the common epsilon 3 allele is not the primal human allele. Rather than accumulating predominantly synonymous nucleotide changes, 50% of substitutions in human and baboon apo E gene coding regions cause amino acid substitutions. However, comparisons of these apo E proteins show conservation of amphipathic helices required for apo E--lipid interactions. The human and baboon apo E genes have diverged less extensively than those from rat and mouse, providing further evidence for a slowing of molecular evolution in primate species. The baboon and rhesus monkey apo E genes (intron 2) contain two Alu repeats that are absent in the human gene, indicating insertion after the divergence of human and cercopithecine lineages, but before the baboon/rhesus divergence. S1 nuclease studies show that transcription of the baboon apo E gene starts at two different positions, one of which corresponds to the human gene start site. To examine linkage of apolipoprotein genes in the baboon genome, we have used a human cDNA probe to detect apo C-I gene sequences approximately 4 kb from the 3' end of the baboon apo E gene.

Amino Acid Sequence↗

Statistical issues in the estimation of assigned shares for carcinogenesis liability.

Congress is currently considering adopting a mathematical formula to assign shares in cancer causation to specific doses of radiation, for use in establishing liability and compensation awards. The proposed formula, if it were sound, would allow difficult problems in tort law and public policy to be resolved by reference to tabulated "probabilities of causation." This article examines the statistical and conceptual bases for the proposed methodology. We find that the proposed formula is incorrect as an expression for "probability and causation," that it implies hidden, debatable policy judgments in its treatment of factor interactions and uncertainties, and that it can not in general be quantified with sufficient precision to be useful. Three generic sources of statistical uncertainty are identified--sampling variability, population heterogeneity, and error propagation--that prevent accurate quantification of "assigned shares." These uncertainties arise whenever aggregate epidemiological or risk data are used to draw causal inferences about individual cases.

Disease Susceptibility↗

Clinical growth standards for Irish children.

A cross-sectional study, measuring height and weight, was performed on a representative sample of 3,509 Irish children aged from 5 to 19 years inclusive. Comparison with other countries showed a significantly later pubertal growth spurt than either the U.K. or the U.S. However, the final adult height and weight are similar to other countries as in the weight-for-height of children aged 5 to 9 years. The urban children are taller than the rural and the higher socio-economic groups are taller than the lower at all ages, but all achieved the same final adult height. Longitudinal tempo-conditional growth standards were constructed based on the Irish cross-sectional and menarche data together with all the available information from longitudinal studies. These charts are similar to those of the U.K., but the use of colours allows more information to be put on the charts, thus making them more suitable for clinical use.

Adolescent↗

Cysteinyl-tRNA synthetase from Bacillus stearothermophilus. A structural and functional monomer.

A procedure is described for the purification of cysteinyl-tRNA synthetase as a side product of a multi-enzyme isolation from Bacillus stearothermophilus. The native and denatured enzyme are both shown to have a molecular weight of 54000 by gel filtration and sodium dodecyl sulphate/polyacrylamide gel electrophoresis respectively. Fingerprinting and peptide counting indicate that the polypeptide chain has a nonrepeating primary structure. The enzyme has only one binding site for each of its substrates (cysteine, ATP and tRNACys) as judged by equilibrium dialysis, active-site titration and fluorescence quenching. No evidence for the dimerisation of the enzyme in the presence of these substrates could be found. We conclude that cysteinyl-tRNA synthetase, which is the smallest aminoacyl-tRNA synthetase yet described, is both structurally and functionally monomeric.

Amino Acids↗

London Archive of Longitudinal Growth Data.

An Archive of longitudinal growth data, accessible to research workers under the usual safeguards, has been set up in the Department of Growth and Development. The present S.I.R. database contains seven British and one Indian study. The Archive is open to receive other contributions if researchers wish.

Adolescent↗