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Biomedical subjects

T Dyer

Publications and source records attributed to T Dyer.

9 recordsLinked to original sources

Respiratory infection and coronary heart disease: progression of a paradigm.

We have developed a previously published paradigm concerning causation of coronary heart disease, based on the probability that the fundamental cause is a microbe, probably Chlamydia pneumoniae, and that the progress of the disease is influenced by number of accelerating and inhibiting factors. We propose that cigarette smoking acts via respiratory infection, this itself being influenced by immunocompetence resulting from sunlight exposure. We also propose an immuno-enhancing effect of oestrogen and an anti-inflammatory effect of statin therapy. In respect of the geographical variation of coronary heart disease, we emphasize that this must be viewed as part of the bigger picture of a high mortality from all causes in countries of North-west Europe that have a particularly low level of sunlight exposure. Finally, we draw attention to the Albanian, French, Italian, Northern Ireland and Scottish paradoxes which should lead to a major review of the conventional wisdom concerning the aetiogenesis of coronary heart disease.

Altitude↗

A prioritisation system for elective coronary angiography.

OBJECTIVE: To devise a clinical prioritisation system for rationing access to a cardiac catheter waiting list and to describe its performance at predicting angiographic findings and selecting patients for angioplasty or coronary artery bypass graft surgery. SETTING: Tertiary level cardiology centre. METHODS: (1) 665 consecutive patients on an elective waiting list for coronary angiography were scored using a system derived from established clinical criteria for selecting patients for coronary surgery (New Zealand/Duke). The scores were compared with clinical outcome (referral for surgery, angioplasty, or medical management). (2) In a subset of 125 patients, scores derived from clinical criteria and exercise testing were compared with findings on coronary angiography. (3) Multivariate analysis was used in a new group of 178 patients to identify factors that would be better predictors of the angiographic score. (4) A new scoring system was devised based partly on the results of the multivariate analysis. It was applied to a new test group of 100 patients using clinical outcome and angiographic score as outcome measures. RESULTS: (1) Using the established clinical score, similar proportions of patients were referred after angiography for medical management, angioplasty, or coronary bypass grafting, irrespective of their original score. The exceptions were patients with a score < 20, who were more likely to continue medical management. (2) There was poor correlation (r = 0.05) between the clinical score and the subsequent angiographic score. (3) Multivariate analysis identified age, male sex, previous myocardial infarction, high cholesterol, and diabetes as independent predictors of coronary score. (4) The modified scoring system, incorporating the predictors identified by multivariate analysis, performed better than the original scoring system in predicting coronary score when both were tested, but some patients had severe disease despite a low score. CONCLUSIONS: Patients can be ranked using clinical and non-invasive criteria, and a rationing system implemented on this basis. With prioritisation by noninvasive criteria, the risk of missing serious coronary disease in patients with relatively mild symptoms must be accepted; this risk becomes greater the more stringently rationing is applied.

Aged↗

Genetics of adult body mass and maintenance of adult body mass in captive baboons (Papio hamadryas subspecies).

Adult body mass and changes in mass during an individual's life are important indicators of general health and reproductive fitness. Therefore, characterization of the factors that influence normal variation in body mass has important implications for colony management and husbandry. The main objective of this study was to quantify the genetic contribution to adult body mass and its maintenance in baboons. Intra-individual mean and variance in body mass were calculated from multiple weight measures available for each of 1,614 animals at least 10 years of age. Heritabilities were estimated using maximum likelihood methods. Mean adult body mass had a significant heritability (50%) as did variance in adult body mass (12%). The sexes differed in several respects: on average females were smaller than males and had greater variability in adult body mass; mean and variance in body mass increased with age in females only; and number of offspring showed a significant positive relationship with body mass in females only. There were significant differences between subspecies in body mass as well as ability to maintain body mass. These results indicate that there is a significant genetic influence on body mass and its maintenance, and suggest that different factors influence changes in body mass with age as well as body mass maintenance in male and female baboons.

Animals↗

Ontogenetic changes in genetic regulation of fetal morphometrics in baboons (Papio hamadryas subspp.).

It is known that different genes are expressed during ontogeny; however, it is unclear how variation in that expression is associated with changes in growth patterns. The objective of this study is to assess how genetic variation in fetal morphology changes with ontogeny in baboons. Longitudinal measures of the head and femur (60 to 180 days gestation) were available for 892 pregnancies. We used a genetic model that allowed both the genetic and environmental variances (sigma 2G and sigma 2E) to change with age and estimated genetic and environmental correlations (rho G and rho E) between measurements at different ages. The results indicate a significant increase in the genetic variance for biparietal diameter and femur length but not for head circumference and fronto-occipital diameter. The rho G estimates for all measures decreased as the age between measures increased from 0 to 120 days, indicating that different groups of genes are expressed early in gestation and late in gestation. The rho E estimates dropped rapidly from 1 to 0 for all measures, indicating temporally localized environmental influences on fetal growth. Thus fetal morphometrics are significantly heritable and those genes that influence them show age-specific expression during ontogeny.

Animals↗

Sunlight, cholesterol and coronary heart disease.

We investigated the relationship between geography and incidence of coronary heart disease, looking at deficiency of sunlight and thus of vitamin D as a factor that might influence susceptibility and thus disease incidence. Sunlight deficiency could increase blood cholesterol by allowing squalene metabolism to progress to cholesterol synthesis rather than to vitamin D synthesis as would occur with greater amounts of sunlight exposure, and the increased concentration of blood cholesterol during the winter months, confirmed in this study, may well be due to reduced sunlight exposure. We show evidence that outdoor activity (gardening) is associated with a lower concentration of blood cholesterol in the summer but not in the winter. We suggest that the geographical variation of coronary heart disease is not specific, but is seen in other diseases and sunlight influences susceptibility to a number of chronic diseases, of which coronary heart disease is one.

Cholesterol↗

Interspecies cross-reactivity of a monoclonal antibody directed against wheat chloroplast fructose-1,6-bisphosphatase.

The primary structure of several chloroplast fructose-1,6-bisphosphatase (CFBPase) was deduced from DNA sequences, but only spinach, pea and rapeseed enzymes have been characterized structurally. We analyzed whether CFBPases from different phylogenetic origin contain a common epitope. To this end a DNA fragment of 1200 base pairs encoding 338 amino acid residues of wheat CFBPase (38 kDa) was cloned in the expression plasmid pGEX-1 in frame with the gene coding for glutathione S-transferase (GT) of Schistosoma japonicun (26.5 kDa). Upon transformation of Escherichia coli and induction with isopropyl-beta-D-thiogalactopyranoside, centrifugation of the lysate partitioned 10% of the fusion protein in the supernatant fraction and the remaining 90% in the precipitate. The expected 65 kDa protein was purified from both the soluble and the particulate fraction by affinity chromatography on columns of glutathione-agarose. This fusion protein was successfully used to produce a monoclonal antibody that specifically recognized the CFBPase region of the fusion protein but not the GT moiety. Moreover, the monoclonal antibody immunoreacted not only with polypeptides (ca. 40 kDa) present in leaf crude extracts of other varieties of wheat (Triticum spelta, T. aestivum and T. durum), but also with homogeneous preparations of the spinach (Spinacia oleracea) and rapeseed (Brassica napus) enzymes. Thus, the cross reaction of this monoclonal antibody with counterparts from different plant species indicates the persistency of a common epitope through biological evolution.

Amino Acid Sequence↗

Pseudohyperkalaemia associated with hereditary spherocytosis in four members of a family.

Pseudohyperkalaemia was detected in four members of a family all of whom have hereditary spherocytosis with normal white blood cells and platelets counts. The degree of pseudohyperkalaemia was related to the time between sampling and cell separation, and inversely related to the temperature in which the sample was left to stand before cell separation. A fifth member of this family was free from both conditions. The association suggests linkage at a membrane level.

Adult↗

Chloroplast fructose-1,6-bisphosphatase: the product of a mosaic gene.

We show here that light stimulates the expression of nuclear genes in wheat leaves for chloroplast fructose-1,6-bisphosphatase (FBPase) and describe a sequence of amino acids in this enzyme which may be responsible, via thioredoxin, for the light regulation of its activity. This data results from (a) our isolation and characterization of a cDNA of this enzyme which contains its entire coding sequence, and (b) our use of this cDNA as a probe to detect mRNA levels in wheat plants subjected to different light regimes. The similarity in amino acid sequence of the encoded enzyme from diverse sources suggests that the FBPase genes all had a common origin. However, their control sequences have been adjusted so that they are appropriately expressed and their coding sequences modified so that the enzymic activity of their products are suitably regulated in the particular cellular environment in which they must function. The light-activated regulatory sequences in the gene for the chloroplast protein have probably come together by a shuffling of DNA segments.

Amino Acid Sequence↗