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M Steel

Publications and source records attributed to M Steel.

13 recordsLinked to original sources
PubMed1995

A frequency-dependent significance test for parsimony.

We describe techniques for assessing evolutionary trees constructed by the parsimony criteria, when sequences exhibit irregular base compositions. In particular, we extend a recently described frequency-dependent significance test to handle any number of taxa and describe a modification of the Kishino-Hasegawa sites test. These modifications are useful for detecting historical signals beyond those patterns which arise purely from irregular base compositions between the compared sequences. We apply the test to extend our earlier studies on chloroplast origins using 16S rDNA sequences, where a failure to compensate for irregular base compositions between the compared sequences provides statistically significant support for unjustified phylogenetic inferences. We also describe how the techniques can be modified to determine how "tree-like" data are, given independent variation in the base frequencies.

Models, Statistical↗
PubMed1995

Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens.

New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general "landscape" of trees. Over 1,000 searches were made from random starting trees with only one tree (a local optimum) being retained each time, thereby ensuring optima were found independently. A new tree comparison metric was developed that is unaffected by rearrangements of trees around many very short internal edges. Use of this metric showed that downweighting hypervariable sites revealed more evolutionary structure than studies that weighted all sites equally. Our results are consistent with convergence toward a global optimum. Crucial features are that the best optima show very strong regional differentiation, a common group of 49 African sequences is found in all the best optima, and the best optima contain the 16 !Kung sequences in a separate group of San people. The other 86 sequences form a heterogeneous mixture of Africans, Europeans, Australopapuans, and Asians. Thus all major human lineages occur in Africa, but only a subset occurs in the rest of the world. The existence of these African-only groups strongly contradicts multiregional theories for the origin of Homo sapiens that require widespread migration and interbreeding over the entire range of H. erectus. Only when the multiregional model is rejected is it appropriate to consider the root, based on a single locus, to be the center of origin of a population (otherwise different loci could give alternative geographic positions for the root). For this data, several methods locate the root within the group of 49 African sequences and are thus consistent with the recent African origin of H. sapiens. We demonstrate that the time of the last common ancestor cannot be the time of major expansion in human numbers, and our results are thus also consistent with recent models that differentiate between the last common ancestor, expansion out of Africa, and the major expansion in human populations. Such a two-phase model is consistent with a wide range of molecular and archeological evidence.

Africa↗
PubMed1992

Endocrine parameters associated with disruption of parturition after bilateral pelvic neurectomy.

Bilateral lesions of the pelvic nerve (BLPN) result in dystocia, but the processes which control this effect are not fully understood. Plasma progesterone, relaxin, and luteinizing hormone (LH) concentrations were measured in blood samples taken in the morning (AM) and evening (PM) of Days 20-23 of gestation from rats with BLPN or sham neurectomy. Ten of 11 sham-operated control animals delivered their entire litters by Day 23 of gestation, but animals with BLPN did not complete parturition by Day 23 when they were sacrificed. Progesterone concentrations were greater in rats with BLPN than in sham-operated rats on Day 20 PM and Day 21 AM, but hormone concentrations declined to minimal values by Day 22 in both groups. Relaxin concentrations were greater in rats with BLPN than in sham-operated rats on Day 21 PM. Thereafter, relaxin concentrations decreased to reach minimum values on Day 23 in both groups. LH concentrations were low throughout the period of study in rats with BLPN; however, a postpartum LH surge was detected in all sham-operated animals. Data from this study indicate that the pelvic nerve does not control parturition by modulating serum relaxin and progesterone concentrations; however, these data suggest that impulses carried by the pelvic nerve influence ovarian secretion of these hormones. In addition, these data indicate that the pelvic nerve transmits stimuli from the cervix to the hypothalamus to facilitate the postpartum LH surge.

Animals↗
PubMed1991

Genetic aspects of breast cancer.

Of all the factors contributing to breast cancer risk, a strong family history of the disease is the most powerful. Familial clustering is said to have been noted by the Ancient Romans but formal documentation began in the mid-nineteenth century (reviewed in Ref. 1). The French physician Paul Broca noted that in one family (probably his wife's) over four generations 10 out of 24 women had died from breast cancer while several more individuals, of both sexes, had suffered other malignancies. He concluded that this very large excess of cancers could not reasonably be attributed to chance. At the same time he recognized that occasional familial clusters of relatively common conditions would be expected even in the absence of any genetic predisposition and discounted several published reports of 'hereditary cancers', including some of the families collected by his English contemporary Sir James Paget.

Breast Neoplasms↗
PubMed1990

Failure of ADCC to predict HIV-associated disease progression or outcome in a haemophiliac cohort.

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been described in a number of virus infections and occurs in HIV infection. In spite of numerous studies on the ability of HIV-positive sera to mediate ADCC, it remains unclear whether ADCC has any functional significance. Here we examine serial serum samples from a cohort of haemophilia patients who became infected from a common source in 1984, and show that there is no significant difference in ADCC values between those who remained asymptomatic and those who progressed to disease. This study does not compare effector cell function and clinical status and does not exclude activity against different target cell lineages in vivo.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1988

Butter-enriched diets reduce arterial prostacyclin production in rats.

Rats were fed diets containing 10%, 30% or 50% energy as fat derived predominantly from butter or lard. The protein content of the diets was maintained at 20%. After three weeks on the diets, the rats were killed and the following parameters measured: prostacyclin production in vitro from abdominal aorta and mesenteric artery; platelet aggregation to ADP and thrombin; fatty acid composition of the phospholipids in plasma, thoracic aorta and liver; smooth muscle reactivity and release of endothelial derived relaxing factor (EDRF) from aortic endothelium stimulated by acetylcholine. There was no significant effect of increasing fat content of the diets (neither lard nor butter) on platelet aggregation. In contrast, prostacyclin production in both the mesenteric artery and the abdominal aorta fell in a concentration-dependent manner in the butter-supplemented rats. However, no effect on prostacyclin production was detected in arteries from the lard-supplemented animals. The effects of the diets on prostacyclin (PGI2) production correlated very well with the changes in plasma, aortic and liver phospholipid arachidonic acid (AA) and eicosapentaenoic acid (EPA) contents. AA decreased in a concentration-dependent manner in the rats fed the butter-enriched diets but did not change in those fed the lard-enriched diets, whereas EPA rose in a concentration-dependent manner in the butter-fed rats and was unchanged in the lard-fed animals. The clear-cut effects of the butter-enriched diets on aortic phospholipid fatty acid composition and aortic PGI2 production were accompanied by a significant reduction in smooth muscle relaxation to EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Differences in genetic stability between human cell lines from patients with and without lymphoreticular malignancy.

Isoenzymes determined by 11 loci have been examined in 137 human lymphoblastoid lines of various origins with a view to determining their phenotypic stability in culture. Lines of normal origin are stable and at these loci are phenotypically identical to the individuals from whom they are derived. Lymphomas and some lines from patients with leukaemias show a tendency to increased apparent homozygosity, presumably resulting from loss of expression of one or other allele during culture. Taken together with the cytogenetic evidence this suggests that progressive loss of functional parts of the genome with time in culture is a characteristic of lines derived from malignant lymphoid cells.

Burkitt Lymphoma↗
PubMed1974

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England↗