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Biomedical subjects

M Steel

Publications and source records attributed to M Steel.

At least 55 records · Page 3Linked to original sources

Differential cytokine production associated with distinct phases of murine graft-versus-host reaction.

Previous studies which demonstrated that cytokines such as interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are essential for the development of graft-versus-host reaction (GvHR) did not establish whether the individual cytokines were responsible for distinct features of the disease. In this report, we show that IFN-gamma production is associated with the early proliferative phase of the disease, whereas the late, destructive phase correlates with production of TNF-alpha. These studies may assist in the development of specific immunotherapies aimed at individual aspects of immunologically mediated disease.

Animals↗

A role for interleukin-1 alpha in immunologically mediated intestinal pathology.

Interleukin-1 (IL-1) is an important mediator of inflammation and has been implicated in several forms of immunopathology. Here we have investigated whether IL-1 plays a role in the enteropathy which occurs during a graft-versus-host reaction (GVHR) in mice. Non-irradiated (CBA x BALB/c) F1 mice with GVHR had increased production of IL-1 and treatment with rabbit anti-IL-1 alpha antibodies abolished the crypt hyperplasia and significantly reduced the parallel increase in crypt length which occurs in the jejunum. Antibody treatment had no effect on the accompanying increase in intraepithelial lymphocyte (IEL) counts or on the splenomegaly. Recombinant IL-1 itself produced villus atrophy, crypt hyperplasia and increased IEL counts in normal mice and stimulated the proliferation of an intestinal epithelial cell line in vitro. We propose that IL-1 plays an effector role in immunologically mediated enteropathy, either via direct effects on epithelial cells or secondary to an action on other, stromal cells in the mucosa.

Animals↗

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↗

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↗

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↗

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↗

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↗

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England↗

Forearm arterial vascular responsiveness in insulin-dependent diabetic subjects.

The vascular reactivity of forearm arterioles was measured in 16 control subjects (C) and 30 insulin-dependent diabetic (IDDM) subjects, 16 of whom were shown to have microvascular and/or neuropathic complications (DC) including 8 with autonomic neuropathy (DCa) and 14 were shown to be free of complications (DNC). Forearm blood flow was measured by strain gauge plethysmography basally, following a cold pressor stress and following a period of arterial occlusion (reactive hyperaemia). The tests were repeated 24 h later following aspirin treatment. Both C and DNC showed a significant reduction in blood flow in the cold pressor test (C 0.64 +/- 0.12, DNC 0.89 +/- 0.22 ml/100 ml forearm tissue/min reduction in flow P < 0.005), while DC showed no significant response. Reactive hyperaemia was significantly greater in C than in DNC or DC (8.37 +/- 1.14, 5.51 +/- 1.27 and 4.95 +/- 0.75 ml/100 ml tissue/min, respectively, P < 0.02). In the DC group, DCa had significantly less response than those without autonomic neuropathy. Aspirin treatment restored the response of DNC but not DC to normal, suggesting that the abnormality in the former group may have been due to overproduction of a vasoconstrictive cyclooxygenase product (such as thromboxane A2). It is concluded that the abnormalities of vasomotor responses in diabetic subjects are complex and are apparently dependent on autonomic neuropathy, humoral and perhaps structural changes.

Adult↗