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R H Stead

Publications and source records attributed to R H Stead.

47 records · Page 3Linked to original sources
PubMed1977

Feulgen microdensitometry and analysis of S-phase cells in cervical tumour biopsies.

Tissue specimens from the cervical tumours of 70 patients undergoing radiotherapy were examined by Feulgen microdensitometry. Twenty-five of the 70 specimens were also subjected to in-vitro tritiated thymidine autoradiography to determine the proportion of DNA synthesising cells they contained. A spectrum of frequency distributions of nuclear DNA content was obtained from Feulgen microdensitometry, but by inspecting the data the basic DNA content of malignant cells could be established in most cases. Fifty-nine per cent of the tumours were 'diploid', 10% 'tetraploid', 13% 'diploid to tetraploid', and the remaining 18% 'aneuploid'. Grafical analysis of DNA frequencies from 48 'diploid' or 'tetraploid' tumours enabled the proportion of DNA synthesising (S) cells to be estimated by frequency distribution analysis. Estimates of the S component ranged from nil to 30%, were log normally distributed, and comparable to direct measurements of cells in S determined by autoradiography for 25 cases (range 1.2-28.7%). For all paired data the mean difference was 1.2 +/- 1.45% (confidence limits), suggesting that overall Feulgen microdensitometry analysis may be an equally valid technique in providing cellular kinetic information with human tumour material.

Autoradiography↗
PubMedDate not supplied

The mast cell-nerve axis in wound healing: a hypothesis.

Beyond their classic roles in allergic reactions and defence against parasites, mast cells can now be viewed as key players in regulating connective tissue homeostasis. There is good evidence that mast cells are in close morphological and functional contact with the peripheral nervous system. Although substantial differences exist between mast cells of different tissues and different species, they produce a wide range of agents, including cytokines, growth factors, and other regulatory molecules, and they respond to an equally wide range of substances, including neuropeptides. At our current level of understanding wound healing, inflammation plays a central role in this process, with macrophages being central protagonists at the cellular level. There is now increasing evidence that mast cells are also involved in wound healing, in health and disease. They produce and secrete histamine, heparin, and multifunctional cytokines and growth factors, which represent important agents in the wound-healing process. Reviewing the recent literature supporting this hypothesis, we also outline the clinical importance of this work to help close the gap between basic research and clinical application.

Animals↗
PubMedDate not supplied

Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosa.

Mast cells degranulate when exposed to specific antigens (via surface bound IgE), resulting in the release of numerous pro-inflammatory mediators. Neuroregulatory substances also activate mast cells, and may effect differential mediator release, without degranulation, suggesting a role for nerves in modulating mast cell activity. We previously investigated the microanatomical relationships of intestinal mucosal mast cells (IMMC) with nerves and found extensive associations in the intestinal mucosae of rats and humans. The origins of nerves that contact IMMC have not been determined; however, recent morphological and functional studies suggest the possibility that the vagus nerve might be involved. In the current study we show that vagal afferent fibers (labeled by injecting DiI into the nodose ganglion) penetrate to the tips of jejunal villi; and that some of these nerves make intimate contact with IMMC. These data provide the microanatomical basis for direct neural communication between the central nervous system (CNS) and mast cells in the gastrointestinal mucosa.

Afferent Pathways↗
PubMedDate not supplied

Neuroendocrine regulation of mucosal immunity.

In view of the extensive innervation of the gastrointestinal tract, including the mucosa, and the high number of immune effector cells present in this tissue, we have studied the effects of certain neurotransmitters on immune responses. We have concentrated on the effects of the neuropeptides substance P (SP), somatostatin (SOM) and vasoactive intestinal peptide (VIP). We have found that SP causes an increase in the proliferation of Peyer's patch lymphocytes as well as immunoglobulin (especially IgA) synthesis, when compared to splenic cells; and that there is a greater expression of SP receptors on lymphocytes derived from Peyer's patches compared to the spleen, without a significant difference in the expression between subsets of T and B cells. Furthermore, we have shown that intraepithelial leukocytes (IEL) show significantly increased cytotoxic activity following incubation with SP; whereas splenic lymphocytes were not stimulated in the same system. The effects of SOM where bi-directional depending upon the concentration employed but in general, SOM was inhibitory, in terms of proliferation, as was VIP. Although many more experiments are required to prove a physiological significance for the results that we have obtained, and to examine the whole gamut of neurotransmitters, we suggest that neuroendocrine regulation may play an important part in mucosal immunity.

Animals↗
PubMedDate not supplied

Innervation of mucosal immune cells in the gastrointestinal tract.

There is mounting evidence for interactions between the immune and peripheral nervous systems. Many regulatory molecules are candidate mediators for communication between inflammatory cells and nerves; however, the extent of targeting of neurotransmitters (and interleukins) as intersystem messengers has been somewhat overlooked. Lymphoid tissues are well supplied by nerves and the gastrointestinal lamina propria, which is populated by a variety of immune cell types, is densely innervated. One-half to two-thirds of mast cells are closely apposed to nerves in the intestinal mucosa, in both rodents and humans, and nerve stimulation has been reported to cause mast cell activation. Although less extensively studied, both eosinophils and plasma cells in the gastrointestinal mucosa are also positioned for interaction with nerves, and intra-epithelial leukocytes may be subject to diffusible neurally-derived mediators. Peyer's patches are relatively sparsely innervated but appear to express neuropeptide receptors in inflammatory conditions. Although the nerves in the mucosa have traditionally been thought of as a static component, recent experiments suggest that these may undergo extensive remodelling during nematode-induced inflammation. Such data suggest a dynamic interplay between the immune and nervous systems during inflammatory episodes in the gut, although considerable work is still needed to determine the importance of neuro-immune interactions in gastrointestinal homeostasis and inflammation.

Animals↗