Biomedical subjects

A Robins

Publications and source records attributed to A Robins.

At least 19 recordsLinked to original sources

PubMed2006

Sustainable waste management in the UK: the public health role.

This paper discusses waste management in the UK and its relationship with health. It aims to outline the role of health professionals in the promotion of waste management, and argues for a change in their role in waste management regulation to help make the process more sustainable. The most common definition of sustainable development is that by the Brundtland commission, i.e. "development that meets the needs of the present without compromising the ability of future generations to meet their own needs". Managing waste sites in a manner that minimises toxic impacts on the current and future generations is obviously a crucial part of this. Although the management of waste facilities is extremely complex, the Integrated Pollution Prevention and Control regime, which requires the input of public health professionals on the regulation of such sites, means that all waste management installations should now be operating in a fashion that minimises any toxicological risks to human health. However, the impacts upon climate change, resource use and health inequalities, as well as the effects of waste transportation, are currently not considered to be part of public health professionals' responsibilities when dealing with these sites. There is also no requirement for public health professionals to become involved in waste management planning issues. The fact that public health professionals are not involved in any of these issues makes it unlikely that the potential impacts upon health are being considered fully, and even more unlikely that waste management will become more sustainable. This paper aims to show that by only considering direct toxicological impacts, public health professionals are not fully addressing all the health issues and are not contributing towards sustainability. There is a need for a change in the way that health professionals deal with waste management issues.

Community Health Planning↗

PubMed2006

Dendritic cell biology, dysfunction and immunotherapy in gastrointestinal cancers.

Gastrointestinal (GI) cancers make up a significant proportion of newly diagnosed malignant disease. The five-year survival for these GI cancers is poor. Anti-cancer host defences are thought to play a role in these cancers, albeit they are suboptimal. Novel immunotherapies are being introduced to treat such patients. This review describes basic cell biology of dendritic cells, as they are thoughtto play a key role in generating effective anti-tumour responses. Dendritic cell dysfunction in patients with various cancers is documented and immunotherapy using dendritic cells in a range of GI cancers is described and discussed

Dendritic Cells↗

PubMed2004

Sustainable development of urban transport systems and human exposure to air pollution.

DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment, http://www.dapple.org.uk) is a major research project that will provide the understanding necessary to assess the sustainability of urban road transport in terms of exposure to traffic-related air pollution as an alternative to current indicators based on emissions, roadside, or far-from-road air pollution levels. The methodology is described, which combines on-street and laboratory measurement with modelling of the movement of air, vehicles, and vehicle exhaust emissions. The relationship between this kind of assessment and more realistic indicators of sustainability is discussed. The value of large-scale interdisciplinary research in this area is thus demonstrated.

Air Movements↗

PubMed2004

Introduction to the DAPPLE Air Pollution Project.

The Dispersion of Air Pollution and its Penetration into the Local Environment (DAPPLE) project brings together a multidisciplinary research group that is undertaking field measurements, wind tunnel modelling and computer simulations in order to provide better understanding of the physical processes affecting street and neighbourhood-scale flow of air, traffic and people, and their corresponding interactions with the dispersion of pollutants at street canyon intersections. The street canyon intersection is of interest as it provides the basic case study to demonstrate most of the factors that will apply in a wide range of urban situations. The aims of this paper are to introduce the background of the DAPPLE project, the study design and methodology for data collection, some preliminary results from the first field campaign in central London (28 April-24 May 2003) and the future for this work. Updated information and contact details are available on the web site at http://www.dapple.org.uk.

Air Pollution↗

PubMed2003

Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (II).

The precise cause(s) of Crohn's disease and ulcerative colitis are unknown. From animal models and human studies it is well established that gut bacterial flora are essential for inducing the bowel inflammation. Animal models, when kept in a germ-free environment, do not develop colitis until the gut flora is reconstituted. It is not clear whether the bacterial antigens (Ags) from the normal flora or some other pathogenic bacterial Ags induce/propagate the inflammatory process in inflammatory bowel disease (IBD). Despite extensive research it has not been possible to identify any specific bacteria or virus as a credible cause of IBD. Recent understanding of quorum sensing molecules (QSMs) secreted by bacteria helps to explain the community behaviour in bacterial species. When QSMs reach a defined concentration, they activate bacterial proliferation and a number of virulence genes. Also, these molecules have been found to modulate the immune system to the advantage of the gut bacteria. They have not been well studied, however, in the gut. Inappropriate secretion of QSMs may alter the gut-associated lymphoid tissue (GALT) and, thereby, deregulate the immune tolerance normally present. Usefulness of probiotics and their immune modulating effects are being increasingly reported. Probiotics are also being used in the treatment of IBD. The interaction between the epithelial cells and the gut flora is very important as this is the first line of contact; this interaction may determine the induction of tolerance and mucosal integrity or immune activity, tissue inflammation and abnormal permeability. The latter is documented in patients with IBD and their healthy relatives. This may be an important factor in disruption of mucosal integrity and GALT dysfunction.

Animals↗

PubMed2003

Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (I).

Gut-associated lymphoid tissue (GALT) is the largest lymphoid organ in the body. This is not surprising considering the huge load of antigens (Ags) from food and commensal bacteria with which it interacts on a daily basis. Gut-associated lymphoid tissue has to recognise and allow the transfer of beneficial Ags whilst concurrently dealing with and successfully removing putative and overtly harmful Ags. This distinctive biological feature of GALT is believed to be crucial to good health. Deregulation or dysfunction of GALT is thought to predispose to inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. The exact mechanism(s) underlying the pathogenesis of IBD is (are) poorly understood and the immunological defects in GALT are poorly documented. Advances in immunology have highlighted the importance of dendritic cells (DCs), which are the key Ag presenting cells in tissues and lymphoid compartments. Their crucial role in GALT, in health and disease is discussed in this review. Interaction of DCs with T cells in the gut produces a subset of T lymphocytes, which have immunosuppressive function. Inappropriate Ag uptake and presentation to naïve T cells in mesenteric lymph nodes may lead to T cell tolerance in GALT. These various complex factors in the gut are discussed and their possible relevance to IBD evaluated.

Dendritic Cells↗

PubMed2003

Assessment of Be1 and Be2 cells in systemic lupus erythematosus indicates elevated interleukin-10 producing CD5+ B cells.

Recent studies indicate that normal B cells can be primed to differentiate into two distinct cytokine-secreting effector subsets, Be1 and Be2. The aim of this study was to analyse, for the first time, Be1 and Be2 cells at the single cell level in SLE patients using the recently developed technique of flow cytometry for intracellular cytokines. Peripheral blood mononuclear cells (PBMC) from SLE patients and age- and sex-matched normal controls were cultured for 24 h in the presence or absence of phorbal myristate acetate and ionomycin (PMA/I) or lipopolysaccharide (LPS). The production of type I (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-6, IL-10, IL-13) cytokines by B cells (and IL-10 production by fractionated CD5+ and CD5- B cells) was investigated using an intracellular cytokine staining technique and flow cytometry. In the absence of PMA/I stimulation, the percentage of B cells from SLE patients was significantly lower than those of normal subjects and significantly more SLE B cells spontaneously produced IL-10 than controls. Moreover, CD5+ B cells from SLE patients were enriched for cells with signs of previous in vivo activation and for high levels of IL-10 production. A significant positive correlation was observed between the percentage of IL-10- and IL-6-producing PMA/I-stimulated B cells in SLE patients, but not in controls. There were no significant differences in the production of other cytokines by B cells of SLE patients and normal subjects. In conclusion, a general alteration of type 1 and type 2 cytokine production by B cells is not observed in SLE patients. The role of B cell cytokines in the pathogenesis of SLE appears to be exerted by elevated secretion of in vivo IL-10, which may play an important role in the immune dysregulation observed in SLE patients. Moreover, the cross regulation of IL-10 and IL-6 is disrupted in SLE patients.

B-Lymphocytes↗

PubMed2002

Characterization of humoral and cellular immune responses elicited by meningococcal carriage.

In order to study the immune response elicited by asymptomatic carriage of Neisseria meningitidis, samples of serum, peripheral blood mononuclear cells (PBMCs), and saliva were collected from a cohort of more than 200 undergraduate students in Nottingham, United Kingdom, who were subject to high rates of acquisition and carriage of meningococci. Serum immunoglobulin G levels were elevated following increases in the rate of carriage, and these responses were specific for the colonizing strains. In order to investigate T-cell responses, PBMCs from 15 individuals were stimulated with a whole-cell lysate of the H44/76 meningococcal strain (B:15:P1.7,16), stained to detect cell surface markers and intracellular cytokines, and examined by flow cytometry. The cells were analyzed for expression of CD69 (to indicate activation), gamma interferon (IFN-gamma) (a representative T-helper 1 subset [Th1]-associated cytokine), and interleukin-5 (IL-5) (a Th2-associated cytokine). Following a brief meningococcal stimulation, the numbers of CD69(+) IFN-gamma(+) CD56/16(+) NK cells were much higher than cytokine-positive CD4(+) events. Both IFN-gamma(+) and IL-5(+) events were detected among the CD69(+) CD4(+) population, leading to the conclusion that an unbiased T-helper subset response was elicited by meningococcal carriage.

Antibodies, Bacterial↗

PubMed2001

Human T cell subset commitment determined by the intrinsic property of antigen: the proteolytic activity of the major mite allergen Der p 1 conditions T cells to produce more IL-4 and less IFN-gamma.

The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 elicits IgE antibody responses in a significant proportion of patients suffering from dust mite allergy. We have recently shown that Der p 1 proteolytically cleaves a cell surface molecule involved in the homeostatic control of human IgE synthesis, namely the IL-2 receptor (CD25) on T cells. As a result, these T cells show markedly diminished proliferation and IFN-gamma secretion in response to stimulation by anti-CD3 antibody. However, these observations still leave open the important issue of whether CD25 cleavage, and the consequent suppression of IFN-gamma secretion, leads to enhanced IL-4 secretion, and whether such cytokine changes would be exhibited by both CD4 and CD8 T cells. Here we demonstrate for the first time that the proteolytic activity of Der p 1 biases human CD4 and CD8 T cells towards a type 2 cytokine profile. Our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis.

Allergens↗

PubMed2001

Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8(-) and CD8(+) T cells in systemic lupus erythematosus.

The production of type 1 (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-10, IL-13) cytokines by CD8(-) and CD8(+) T cells from systemic lupus erythematosus (SLE) patients and normal subjects was investigated using an intracellular cytokine-staining technique. This flow cytometric method facilitates analysis of both surface markers and cytoplasmic cytokines, after a short term (6 h) culture with or without phorbol myristate acetate and ionomycin (PMA/I) stimulation. In SLE patients, more unstimulated T cells produced IL-10 in comparison with controls; other cytokines were not detected in unstimulated cells. The percentage of IL-10-secreting T cells did not significantly increase after PMA/I stimulation of cells from SLE patients. The mean intensity of fluorescence (MIF) of intracellular IL-4 staining was significantly higher in CD8(-) T cells of SLE patients than controls. Significantly fewer CD8(-) and CD8(+) T cells from SLE patients secreted IFN-gamma after PMA/I stimulation compared with controls. The MIF and percentage of IL-2, IL-5, and IL-13-secreting cell subsets were not significantly different between SLE patients and controls. These findings indicate that T cells of SLE patients are already stimulated to produce IL-10 in vivo, which may result in downregulation of IFN-gamma secreting CD8(-) and CD8(+) T cells observed following PMA/I stimulation. Thus, the population size of Th1 and Tc1 cells are reduced in SLE patients whereas the effector function of Th2 cells, with respect to IL-4 production, is enhanced in SLE patients. Furthermore, although the balance between Th1/Th2 and between Tc1/Tc2 is disrupted in SLE patients, it is significantly biased in favour of the Th2 subset only.

Adult↗

PubMed1999

The consolidation of learning during sleep: comparing the pseudorehearsal and unlearning accounts.

We suggest that any brain-like (artificial neural network based) learning system will need a sleep-like mechanism for consolidating newly learned information if it wishes to cope with the sequential/ongoing learning of significantly new information. We summarise and explore two possible candidates for a computational account of this consolidation process in Hopfield type networks. The "pseudorehearsal" method is based on the relearning of randomly selected attractors in the network as the new information is added from some second system. This process is supposed to reinforce old information within the network and protect it from the disruption caused by learning new inputs. The "unlearning" method is based on the unlearning of randomly selected attractors in the network after new information has already been learned. This process is supposed to locate and remove the unwanted associations between information that obscure the learned inputs. We suggest that as a computational model of sleep consolidation, the pseudorehearsal approach is better supported by the psychological, evolutionary, and neurophysiological data (in particular accounting for the role of the hippocampus in consolidation).

Journal Article↗

PubMed1999

Catastrophic forgetting in simple networks: an analysis of the pseudorehearsal solution.

Catastrophic forgetting is a major problem for sequential learning in neural networks. One very general solution to this problem, known as 'pseudorehearsal', works well in practice for nonlinear networks but has not been analysed before. This paper formalizes pseudorehearsal in linear networks. We show that the method can fail in low dimensions but is guaranteed to succeed in high dimensions under fairly general conditions. In this case an optimal version of the method is equivalent to a simple modification of the 'delta rule'.

Algorithms↗

PubMed1998

Complementary right and left hemifield use for predatory and agonistic behaviour in toads.

Cerebral lateralization, the differing specializations of the right and left sides of the brain once thought to be unique of humans, is now well known to occur in both birds and mammals. Here we report that in toads the right hemisfield of vision guides predatory tongue-striking responses towards moving prey and the left hemisfield guides agnostic tongue-striking responses towards conspecifics. This indicates, for the first time, complementary cerebral specializations for visual processing in anurans, and strongly supports the hypothesis that lateralized brain functions in birds and mammals may have arisen from a common lateralized ancestor. Complementary specializations in visual processing may have originally evolved to avoid problem of response competition during control of medial organs such as the tongue in organisms with laterally placed eyes and, in organisms with wider binocular overlap, it appears to be retained for initial detection of stimuli in the extreme lateral fields.

Agonistic Behavior↗

PubMed1998

A novel flow cytometric assay for quantitating adherence of Helicobacter pylori to gastric epithelial cells.

Adherence may be an important virulence factor for Helicobacter pylori. Current methods available for quantitation of adherence are time consuming and liable to observer error. A new direct technique for fluorescent labelling of bacteria has been developed to quantitate adherence of H. pylori to epithelial cells by fluorescence activated cell sorting (FACS). Type strains of H. pylori, H. mustelae, H. cinaedi and H. fennelliae were grown microaerobically in broth culture for 24 h and fluorescently labelled by incubation with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) at 37 degrees C. After washing to remove excess CFDA-SE, bacteria were co-incubated (ratio 10:1) with gastric epithelial cells at 37 degrees C for up to 24 h. After washing to remove non-adherent bacteria, epithelial cells were detached with EDTA (2 mM) and fixed with formaldehyde for flow cytometry. Adherence was quantitated both in terms of the proportion of cells with adherent H. pylori and as the mean number of adherent bacteria per cell. All H. pylori strains adhered to gastric-type epithelial cells. The proportion of cells with bound bacteria varied from 40-99% and the number of bacteria per cell from 1-50, both of which correlated with microscopy (r = 0.6, and r = 0.8 respectively, n = 35). Time course studies demonstrated saturation of binding by H. pylori within 90 min. For H. mustelae, H. cinaedi and H. fennelliae the proportion of cells with bound bacteria varied from 5-15% and the mean number of bacteria per cell was < 4. Binding of H. pylori to epithelial cells could be partly blocked by pre-incubation with polyclonal anti-sera or using oligosaccharides against potential binding epitopes of gastric mucus. Fluorescent labelling of H. pylori with CFDA-SE in combination with flow cytometry provides a quick, specific, and sensitive method to quantitate in vitro the adherence of H. pylori.

Antibodies, Bacterial↗

PubMed1998

Lateralized agonistic responses and hindlimb use in toads.

The recent discovery of forepaw preferences (handedness) in toad species has provided some insight into the evolution of brain lateralization. We tested the prediction that, as in higher vertebrates, visual lateralization and other motor preferences (footedness) also exists in toad species. During feeding periods, South American cane toads, Bufo marinus, showed a population bias to strike with the tongue at other toads occupying their left visual field. This is the first demonstration of lateralized visual behaviour in an amphibian species. Tongue striking at an individual's eyes or head may sometimes delay its approach to prey already seen by the attacker, or may dislodge prey from its mouth. In addition, we report hindlimb preferences (footedness) for contact righting in three species of toad (B. marinus, the European green toad, B. viridis, and the European common toad, B. bufo). After being fully overturned on to their back on a horizontal surface, toads initiated and completed righting using the hindlimbs and with only perfunctory use of the forepaws. Together, the findings of visual lateralization and footedness demonstrate that in toads, as in higher vertebrates, behavioural lateralization is not restricted to handedness. The hypothesis that lateralized brain functions in birds and mammals might have arisen from a common lateralized ancestor is therefore supported. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed1998

Quantification of insulin-like growth factor I receptors on granulosa cells with flow cytometry after follicular stimulation.

The presence of insulin-like growth factor I (IGF-I) receptors on granulosa cells was investigated by flow cytometric analysis. Granulosa cells were retrieved from follicular fluid after oocyte retrieval during assisted reproduction technology procedures. Whole samples of follicular fluid were pooled and the cellular fraction analysed. In order to analyse granulosa cells only we developed a dual labelling technique whereby granulosa cells were identified as CD45 negative cells, distinguishing them from leukocytes which are CD45 positive. Analysis of the IGF-I receptor was done by staining the sample with a monoclonal anti-IGF-I receptor antibody (alphaIR3 clone) and goat anti-mouse phycoerythrin labelled antibody. After identification of the presence of IGF-I receptors, receptor expression was quantified by calibration of the fluorescence signals. We analysed 10 patients' samples and showed 559-1774 binding sites per granulosa cell with a mean value of 1125 +/- 382 (SD).

Female↗

PubMed1998

Isolation, purification and assessment of viability of spermatogenic cells from testicular biopsies of azoospermic men.

The success of spermatid microinjection has generated many concerns. In particular, there is a lack of appropriate methodology for the isolation of large homogeneous populations of spermatids, with minimum loss of viability, from the testicular tissue of azoospermic men. Here we have compared two different isolation methods -- velocity sedimentation under unit gravity (VSUG) combined with discontinuous Percoll centrifugation (DPC), and separation with fluorescent-activated cell sorter (FACS) using light in the visible range -- to determine the most suitable method for the isolation of spermatids. Total mixed cell count/gram of testicular parenchyma was significantly higher in obstructive azoospermic men compared with non-obstructive azoospermic men (P < 0.001). The results of the comparison showed that in obstructive azoospermic patients the difference in the yields of primary spermatocytes produced by the two techniques was not significant, but for round and elongating spermatids the FACS separation proved to be the better method (P < 0.001). Similarly, in non-obstructive azoospermic patients, FACS separation proved to be superior, giving increased yields of primary spermatocytes and round and elongating spermatids compared with VSUG combined with DPC method (P < 0.001). More than 99 % of the separated cells retained their viability after FACS separation. As large homogeneous populations of viable spermatids can be separated with FACS in a relatively short period of time, FACS separation is the most suitable method for the isolation of spermatids from testicular biopsy tissue.

Cell Separation↗

PubMed1997

Pawedness and motor asymmetries in toads.

Pawedness was investigated in three species of toads, Bufo bufo , Bufo viridis , and Bufo marinus. Samples from natural populations were collected in two successive years and tested during attempts to remove a strip of paper stuck onto the snout ( Bufo bufo and Bufo viridis ) or during attempts to remove an elastic balloon wrapped around the head ( Bufo bufo ). A preferential right forelimb use at the population level was observed in Bufo bufo in both tests, whereas no clear pawedness was observed in Bufo viridis. Bufo marinus also showed no laterality in the paper-strip test, but it appeared to be strongly lateralised in another test that investigated which side the toad rotated when turned on its back underwater. Preferentially turning to the toad's left side as part of a righting response, Bufo marinus released the left forelimb first, using the right forelimb to control the roll to the upright position, and push to the surface. These results suggest that preferential limb use has a long evolutionary history, which dates back to early tetrapods.

Journal Article↗