T M Mayhew

University of Nottingham, Nottigham, England, United Kingdom

Are you T M Mayhew?

Claim your profile

Publications (227)611.05 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Systems-based understanding of living organisms depends on acquiring huge datasets from arrays of genes, transcripts, proteins, and lipids. These data, referred to as ‘omes’, are assembled using ‘omics’ methodologies. Currently a comprehensive, quantitative view of cellular and organellar systems in 3D space at nanoscale/molecular resolution is missing. We introduce here the term ‘morphome’ for the distribution of living matter within a 3D biological system, and ‘morphomics’ for methods of collecting 3D data systematically and quantitatively. A sampling-based approach termed stereology currently provides rapid, precise, and minimally biased morphomics. We propose that stereology solves the ‘big data’ problem posed by emerging wide-scale electron microscopy (EM) and can establish quantitative links between the newer nanoimaging platforms such as electron tomography, cryo-EM, and correlative microscopy.
    Trends in Cell Biology. 10/2014;
  • Terry M. Mayhew
    [Show abstract] [Hide abstract]
    ABSTRACT: How the turnover of villous trophoblast is regulated is important for understanding normal and complicated pregnancies. There is considerable accord that syncytiotrophoblast (STB) grows and is refreshed by recruiting post-mitotic cells from the deeper cytotrophoblast (CTB). Nuclei in STB exhibit a spectrum of morphologies and packing densities and, until recently, there seemed to be a consensus that this variation reflected a transition from an early undifferentiated CTB-like phenotype to a long pre-apoptotic and brief apoptotic phase. In these later phases, nuclei are sequestered in clusters (syncytial knots) prior to extrusion as part of normal epithelial turnover. Early in gestation, nuclear clustering and formation of protrusions (syncytial sprouts) also occurs as a preliminary to villous sprouting. Nuclei in these clusters have a CTB-like phenotype and some sprouts may also detach from STB and pass into the uteroplacental circulation. However, this apparent consensus has been challenged and new interpretations of events in the proliferative (CTB), terminal differentiation (STB) and deportation compartments have emerged. Several different types of STB fragment are deported in normal pregnancy: larger multinucleate STB fragments, smaller uninucleate elements with CTB-like morphology and anucleate cytoplasmic fragments and microparticles. This review identifies points of agreement and disagreement and offers possible avenues of future research. An obvious need is to standardize best practice in several areas including choosing appropriate references for cell cycle phase labelling indices and combining immunolabelling of cell cycle and apoptosis markers (at LM or TEM levels) with design-based stereological estimates of absolute numbers of cells and nuclei in different compartments throughout normal gestation. This would also provide a surer foundation for interpreting results from different research groups and changes in normal and complicated pregnancies.
    Placenta 01/2014; · 3.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Body mass (BM) of terrestrial mammalian species ranges from a few grams in the case of the Etruscan shrew to a few tonnes for an elephant. The mass-specific metabolic rate, as well as heart rate, decrease with increasing BM, whereas heart mass is proportional to BM. In the present study, we investigated the scaling behaviour of several compartments of the left ventricular myocardium, notably its innervation, capillaries and cardiomyocytes. Myocardial samples were taken from 10 mammalian species with BM between approximately 2 g and 900 kg. Samples were analysed by design-based stereology and electron microscopy and the resulting data were subjected to linear regression and correlation analyses. The total length of nerve fibres (axons) in the left ventricle increased from 0.017 km (0.020 km) in the shrew to 7237 km (13 938 km) in the horse. The innervation density was similar among species but the mean number of axons per nerve fibre profile increased with rising BM. The total length of capillaries increased from 0.119 km (shrew) to 10 897 km (horse). The volume of cardiomyocytes was 0.017 cm(3) in the shrew and 1818 cm(3) in the horse. Scaling of the data against BM indicated a higher degree of complexity of the axon tree in larger animals and an allometric relationship between total length of nerve fibres/axons and BM. In contrast, the density of nerve fibres is independent of BM. It seems that the structural components of the autonomic nervous system in the heart are related to BM and heart mass rather than to functional parameters such as metabolic rate.
    Journal of Anatomy 12/2013; · 2.36 Impact Factor
  • Source
  • Terry M Mayhew
    [Show abstract] [Hide abstract]
    ABSTRACT: For many organisms, respiratory gas exchange is a vital activity and different types of gas-exchange apparatus have evolved to meet individual needs. They include not only skin, gills, tracheal systems and lungs but also transient structures such as the chorioallantois of avian eggs and the placenta of eutherian mammals. The ability of these structures to allow passage of oxygen by passive diffusion can be expressed as a diffusive conductance (units: cm(3)O(2)min(-1)kPa(-1)). Occasionally, the ability to estimate diffusive conductance by physiological techniques is compromised by the difficulty of obtaining O(2) partial pressures on opposite sides of the tissue interface between the delivery medium (air, water, blood) and uptake medium (usually blood). An alternative strategy is to estimate a morphometric diffusive conductance by combining stereological estimates of key structural quantities (volumes, surface areas, membrane thicknesses) with complementary physicochemical data (O(2)-haemoglobin chemical reaction rates and Krogh's permeability coefficients). This approach has proved valuable in a variety of comparative studies on respiratory organs from diverse species. The underlying principles were formulated in pioneering studies on the pulmonary lung but are illustrated here by taking the human placenta as the gas exchanger.
    Annals of anatomy = Anatomischer Anzeiger: official organ of the Anatomische Gesellschaft 09/2012; · 1.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have shown that particulate matter (PM) compromise birth weight and placental morphology. We hypothesized that exposing mice to ambient PM would affect umbilical cord (UC) morphology. To test this, mice were kept in paired open-top exposure chambers at the same location and ambient conditions but, in one chamber, the air was filtered (F) and, in the other, it was not (NF). UCs were analysed stereologically and by immunohistochemistry to localize isoprostane and endothelin receptors. The cords of mice from NF chambers were smaller in volume due to loss of mucoid connective tissue and decrease in volume of collagen. These structural changes and in umbilical vessels were associated with greater volumes of regions immunostained for isoprostane, ET(A)R and ET(B)R. Findings indicate that the adverse effects of PM on birth weight may be mediated in part by alterations in UC structure or imbalances in the endogenous regulators of vascular tone and oxidative stress.
    Reproductive Toxicology 09/2012; 34(4):598-606. · 3.14 Impact Factor
  • T M Mayhew
    [Show abstract] [Hide abstract]
    ABSTRACT: This study examines both hands of right-handed (dextral) subjects 5-65 years old in order to define the separate growth trajectories of digit lengths (2D-5D) and hand widths; to assess how 2D : 4D and other digit ratios also vary with age; and to test whether lengths are influenced by gender dimorphism and lateral (right/left) asymmetry. Calliper measurements were made from hand photocopies. Growth patterns were analysed by linear regression and correlation, main and interaction effects of age and gender were resolved by analysis of variance, and lateral asymmetries were identified by paired tests. All digits, and hand width, grew in a biphasic pattern in both hands, and inflection points between phases showed gender dimorphism. In the early fast-growing phase, male digits grew over a longer period than those in females, before switching to a slower growth phase during which gender dimorphism became more exaggerated. In right hands, age differences in digit ratios were confined to 2D : 4D and, except for 4D : 5D, females tended to show larger ratios than males. In left hands, all ratios (except 3D : 5D) varied with age and gender influenced only 2D : 4D, 2D : 5D and 3D : 5D. Again, ratios were greater in females. In females, 2D was longer in the right hand of older subjects, whilst 3D, 4D and 5D tended to be shorter in the right hand of younger subjects. No asymmetries were seen in 2D, 3D or 4D in males, but 5D tended to be shorter on the right in the group 9-12 years old. Finally, hand width tended to be greater in females on the right at 9-65 years old, and in males on the right at 18-23 years old. A further novel finding was that certain relationships (inflection points, correlation coefficients and gender differences in digit lengths) seemed to follow gradients running from 2D to 5D. It is tempting to speculate that these are manifestations of the antero-posterior gradients established by signalling events that control digit development and patterning in utero.
    Journal of Anatomy 08/2012; 221(4):373-81. · 2.36 Impact Factor
  • T M Mayhew
    Placenta 04/2012; 33(7):589; author reply 590. · 3.12 Impact Factor
  • Source
    Terry M Mayhew
    [Show abstract] [Hide abstract]
    ABSTRACT: An important tool in cell biology is the combination of immunogold labelling and transmission electron microscopy (TEM) by which target molecules (e.g. antigens) are bound specifically to affinity markers (primary antibodies) and then detected and localised with visualisation probes (e.g. colloidal gold particles bound to protein A). Gold particles are electron-dense, punctate and available in different sizes whilst TEM provides high-resolution images of particles and cell compartments. By virtue of these properties, the combination can be used also to quantify one or more defined targets in cell compartments. During the past decade, new ways of quantifying gold labelling within cells have been devised. Their efficiency and validity rely on sound principles of specimen sampling, event counting and inferential statistics. These include random selection of items at each sampling stage (e.g. specimen blocks, thin sections, microscopical fields), stereological analysis of cell ultrastructure, unbiased particle counting and statistical evaluation of a suitable null hypothesis (no difference in the intensity or pattern of labelling between compartments or groups of cells). The following approaches are possible: (i) A target molecule can be tested for preferential labelling by mapping the localisation of gold particles across a set of compartments. (ii) Data from wild-type and knockdown/knockout control cells can be used to correct raw gold particle counts, estimate specific labelling densities and then test for preferential labeling. (iii) The same antigen can be mapped in two or more groups of cells to test whether there are experimental shifts in compartment labelling patterns. (iv) A variant of this approach uses more than one size of gold particle to test whether or not different antigens colocalise in one or more compartments. (v) In studies involving antigen translocation, absolute numbers of gold particles can be mapped over compartments at specific positions within polarised, oriented or dividing cells. Here, the current state of the art is reviewed and approaches are illustrated with virtual datasets.
    Journal of Anatomy 12/2011; 219(6):647-60. · 2.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The syncytiotrophoblast (STB) epithelial covering of the human placenta is a unique terminally differentiated, multi-nucleated syncytium. No mitotic bodies are observed in the STB, which is sustained by continuous fusion of underlying cytotrophoblast cells (CTB). As a result, STB nuclei are of different ages. Morphologically, they display varying degrees of chromatin compaction, suggesting progressive maturational changes. Until recently, it was thought that STB nuclei were transcriptionally inactive, with all the mRNAs required by the syncytium being incorporated upon fusion of CTB. However, recent research has shown the presence of the active form of RNA polymerase II (RNA Pol II) in some STB nuclei. In this study, we confirm the presence of transcriptional activity in STB nuclei by demonstrating immunoreactivity for a transcription factor and an RNA polymerase I (RNA Pol I) co-factor, phospho-cAMP response element-binding protein and phospho-upstream binding factor, respectively. We also show, through immunoco-localisation studies, that a proportion of STB nuclei are both RNA Pol I and II transcriptionally active. Finally, we quantify the numerical densities of nuclei immunopositive and immunonegative for RNA Pol II in the STB of normal placentas of 11-39 weeks gestational age using an unbiased stereological counting tool, the physical disector. These data were combined with estimates of the volume of trophoblast to calculate total numbers of both types of nuclei at each gestational age. We found no correlation between gestational age and the numerical density of RNA Pol II-positive nuclei in the villous trophoblast (r = 0.39, P > 0.05). As the number of STB nuclei increases exponentially during gestation, we conclude that the number of transcriptionally active nuclei increases in proportion to trophoblast volume. The ratio of active to inactive nuclei remains constant at 3.9:1. These findings confirm that the majority of STB nuclei have intrinsic transcriptional activity, and that the STB is not dependent on CTB fusion for the provision of transcripts.
    Journal of Anatomy 08/2011; 219(5):601-10. · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Altered endothelial function may underlie human cardiovascular diseases, including hypertension, diabetes and pre-eclampsia. While much is known about endothelial function in small arteries, very little is known about endothelial responses in small veins isolated from humans. Therefore, we assessed endothelium-dependent responses in omental arteries and veins isolated from healthy pregnant women, focussing on endothelium-dependent hyperpolarising (EDH) mechanisms. Human omental arteries and veins were obtained from women undergoing elective caesarean sections and examined using pressure myography. In pressurised vessels, the effects of proposed inhibitors of EDH production/function were examined on responses to bradykinin. The expression of connexins Cx37, 40 and 43 was assessed using immunohistochemistry. Bradykinin caused vasodilatation in human pressurised omental arteries and veins. In both vessels, responses to bradykinin were partially blocked in the presence of the gap junction uncoupler, carbenoxolone, and reduced further with the addition of catalase, which acts to degrade H(2)O(2). The effect of catalase alone was more pronounced in venous preparations. All three connexins were expressed in both arteries and veins, with a similar distribution pattern, where Cx37 and Cx40 were located mainly in the endothelium and Cx43 located mostly in the media. These data show that, in human omental vessels, an EDH mechanism is produced in response to bradykinin that involves gap junction communication and the production of H(2)O(2). These mechanisms may be involved in the haemodynamic alterations that take place during pregnancy, and any aberration in their function could contribute to raised blood pressure in hypertensive disorders of pregnancy, such as pre-eclampsia.
    European journal of pharmacology 07/2011; 668(1-2):225-32. · 2.59 Impact Factor
  • Terry M Mayhew
    [Show abstract] [Hide abstract]
    ABSTRACT: A review is presented of recently developed methods for quantifying electron microscopical thin sections on which colloidal gold-labelled markers are used to identify and localize interesting molecules. These efficient methods rely on sound principles of random sampling, event counting, and statistical evaluation. Distributions of immunogold particles across cellular compartments can be compared within and between experimental groups. They can also be used to test for co-localization in multilabelling studies involving two or more sizes of gold particle. To test for preferential labelling of compartments, observed and expected gold particle distributions are compared by χ(2) analysis. Efficient estimators of gold labelling intensity [labelling density (LD) and/or relative labelling index (RLI)] are used to analyse volume-occupying compartments (e.g. Golgi vesicles) and/or surface-occupying compartments (e.g. cell membranes). Compartment size is estimated by counting chance events after randomly superimposing test lattices of points and/or line probes. RLI=1 when there is random labelling and RLI >1 when there is preferential labelling. Between-group comparisons do not require information about compartment size but, instead, raw gold particle counts in different groups are compared by combining χ(2) and contingency table analyses. These tests may also be used to assess co-distribution of different sized gold particles in compartments. Testing for co-labelling involves identifying sets of compartmental profiles that are unlabelled and labelled for one or both of two gold marker sizes. Numbers of profiles in each labelling set are compared by contingency table analysis and χ(2) analysis or Fisher's exact probability test. The various methods are illustrated with worked examples based on empirical and synthetic data and will be of practical benefit to those applying single or multiple immunogold labelling in their research.
    Journal of Experimental Botany 06/2011; 62(12):4101-13. · 5.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present investigation addresses whether the midgut (MG) of Atlantic cod (Gadus morhua L.) is an infection route for Vibrio (Listonella) anguillarum serotype 02 β and if Carnobacterium maltaromaticum, a probiotic bacterium, can out-compete the pathogen and modulate the autochthonous MG microbiota. This was investigated by using an ex vivo method the intestinal sac, utilized previously in studies on Atlantic cod and Atlantic salmon (Salmo salar L.). Exposure of the MG to V. (L.) anguillarum did not reveal any cell damage indicating that the MG does not appear to be an infection route for V. (L.) anguillarum in healthy Atlantic cod. This finding together with previous observations on Atlantic cod and Atlantic salmon indicate that intestine as an infection route might vary between these two species. When the MG was exposed to C. maltaromaticum, no cell damage or cellular disruptions were observed. As budding from the apices of microvilli was observed in all treatments exposed to bacteria, we suggest that budding might be involved in the primary barrier against bacterial infection. However, to clarify this hypothesis, further studies are needed. Exposure of the MG to the probiotics and pathogenic bacteria indicated that C. maltaromaticum, to some extent, is able to out-compete V. (L.) anguillarum but the topic merits further investigation. Analysis of the MG microbiota after sterile saline solution and bacterial exposure indicates that bacteria related to Staphylococcus sciuri belong to the autochthonous gut microbiota in Atlantic cod.
    Aquaculture Research 03/2011; 42(12):1830 - 1839. · 1.42 Impact Factor
  • Terry M Mayhew, John M Lucocq
    [Show abstract] [Hide abstract]
    ABSTRACT: Various methods for quantifying cellular immunogold labelling on transmission electron microscope thin sections are currently available. All rely on sound random sampling principles and are applicable to single immunolabelling across compartments within a given cell type or between different experimental groups of cells. Although methods are also available to test for colocalization in double/triple immunogold labelling studies, so far, these have relied on making multiple measurements of gold particle densities in defined areas or of inter-particle nearest neighbour distances. Here, we present alternative two-step approaches to codistribution and colocalization assessment that merely require raw counts of gold particles in distinct cellular compartments. For assessing codistribution over aggregate compartments, initial statistical evaluation involves combining contingency table and chi-squared analyses to provide predicted gold particle distributions. The observed and predicted distributions allow testing of the appropriate null hypothesis, namely, that there is no difference in the distribution patterns of proteins labelled by different sizes of gold particle. In short, the null hypothesis is that of colocalization. The approach for assessing colabelling recognises that, on thin sections, a compartment is made up of a set of sectional images (profiles) of cognate structures. The approach involves identifying two groups of compartmental profiles that are unlabelled and labelled for one gold marker size. The proportions in each group that are also labelled for the second gold marker size are then compared. Statistical analysis now uses a 2 × 2 contingency table combined with the Fisher exact probability test. Having identified double labelling, the profiles can be analysed further in order to identify characteristic features that might account for the double labelling. In each case, the approach is illustrated using synthetic and/or experimental datasets and can be refined to correct observed labelling patterns to specific labelling patterns. These simple and efficient approaches should be of more immediate utility to those interested in codistribution and colocalization in multiple immunogold labelling investigations.
    Histochemie 02/2011; 135(3):317-26. · 2.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently, superior cervical ganglionectomy has been performed to investigate a variety of scientific topics from regulation of intraocular pressure to suppression of lingual tumour growth. Despite these recent advances in our understanding of the functional mechanisms underlying superior cervical ganglion (SCG) growth and development after surgical ablation, there still exists a need for information concerning the quantitative nature of the relationships between the removed SCG and its remaining contralateral ganglion and between the remaining SCG and its modified innervation territory. To this end, using design-based stereological methods, we have investigated the structural changes induced by unilateral ganglionectomy in sheep at three distinct timepoints (2, 7 and 12 weeks) after surgery. The effects of time, and lateral (left-right) differences, were examined by two-way analyses of variance and paired t-tests. Following removal of the left SCG, the main findings were: (i) the remaining right SCG was bigger at shorter survival times, i.e. 74% at 2 weeks, 55% at 7 weeks and no increase by 12 weeks, (ii) by 7 weeks after surgery, the right SCG contained fewer neurons (no decrease at 2 weeks, 6% fewer by 7 weeks and 17% fewer by 12 weeks) and (iii) by 7 weeks, right SCG neurons were also larger and the magnitude of this increase grew substantially with time (no rise at 2 weeks, 77% by 7 weeks and 215% by 12 weeks). Interaction effects between time and ganglionectomy-induced changes were significant for SCG volume and mean perikaryal volume. These findings show that unilateral superior cervical ganglionectomy has profound effects on the contralateral ganglion. For future investigations, it would be interesting to examine the interaction between SCGs and their innervation targets after ganglionectomy. Is the ganglionectomy-induced imbalance between the sizes of innervation territories the milieu in which morphoquantitative changes, particularly changes in perikaryal volume and neuron number, occur? Mechanistically, how would those changes arise? Are there any grounds for believing in a ganglionectomy-triggered SCG cross-innervation and neuroplasticity?
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 02/2011; 29(4):475-81. · 2.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: During placentation, the concentration of fibrinous deposits on the surfaces of maternal vasculature plays a role in villous development and has been strongly implicated in the pathophysiology of human fetal growth restriction (FGR). Fibrinous deposits are conspicuous sites of platelet aggregation where there is local activation of the hemostatic cascade. During activation of the hemostatic cascade, a number of pro- and antiangiogenic agents may be generated at the cell surface, and an imbalance in these factors may contribute to the placental pathology characteristic of FGR. We tested the hypothesis that angiostatin(4.5) (AS(4.5)), a cleavage fragment of plasminogen liberated at the cell surface, is capable of causing FGR in mice. Increased maternal levels of AS(4.5) in vivo result in reproducible placental pathology, including an altered vascular compartment (both in decidual and labyrinthine layers) and increased apoptosis throughout the placenta. In addition, there is significant skeletal growth delay and conspicuous edema in fetuses from mothers that received AS(4.5). Maternally generated AS(4.5), therefore, can access maternal placental vasculature and have a severe effect on placental architecture and inhibit fetal development in vivo. These findings strongly support the hypothesis that maternal AS(4.5) levels can influence placental development, possibly by directly influencing trophoblast turnover in the placenta, and contribute to fetal growth delay in mice.
    Biology of Reproduction 10/2010; 84(3):505-13. · 4.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously reported outcome-associated decreases in muscle energetic status and mitochondrial dysfunction in septic patients with multiorgan failure. We postulate that survivors have a greater ability to maintain or recover normal mitochondrial functionality. To determine whether mitochondrial biogenesis, the process promoting mitochondrial capacity, is affected in critically ill patients. Muscle biopsies were taken from 16 critically ill patients recently admitted to intensive care (average 1-2 d) and from 10 healthy, age-matched patients undergoing elective hip surgery. Survival, mitochondrial morphology, mitochondrial protein content and enzyme activity, mitochondrial biogenesis factor mRNA, microarray analysis, and phosphorylated (energy) metabolites were determined. Ten of 16 critically ill patients survived intensive care. Mitochondrial size increased with worsening outcome, suggestive of swelling. Respiratory protein subunits and transcripts were depleted in critically ill patients and to a greater extent in nonsurvivors. The mRNA content of peroxisome proliferator-activated receptor γ coactivator 1-α (transcriptional coactivator of mitochondrial biogenesis) was only elevated in survivors, as was the mitochondrial oxidative stress protein manganese superoxide dismutase. Eventual survivors demonstrated elevated muscle ATP and a decreased phosphocreatine/ATP ratio. Eventual survivors responded early to critical illness with mitochondrial biogenesis and antioxidant defense responses. These responses may partially counteract mitochondrial protein depletion, helping to maintain functionality and energetic status. Impaired responses, as suggested in nonsurvivors, could increase susceptibility to mitochondrial damage and cellular energetic failure or impede the ability to recover normal function. Clinical trial registered with clinical trials.gov (NCT00187824).
    American Journal of Respiratory and Critical Care Medicine 09/2010; 182(6):745-51. · 11.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The superior cervical ganglion (SCG) in mammals varies in structure according to developmental age, body size, gender, lateral asymmetry, the size and nuclear content of neurons and the complexity and synaptic coverage of their dendritic trees. In small and medium-sized mammals, neuron number and size increase from birth to adulthood and, in phylogenetic studies, vary with body size. However, recent studies on larger animals suggest that body weight does not, in general, accurately predict neuron number. We have applied design-based stereological tools at the light-microscopic level to assess the volumetric composition of ganglia and to estimate the numbers and sizes of neurons in SCGs from rats, capybaras and horses. Using transmission electron microscopy, we have obtained design-based estimates of the surface coverage of dendrites by postsynaptic apposition zones and model-based estimates of the numbers and sizes of synaptophysin-labelled axo-dendritic synaptic disks. Linear regression analysis of log-transformed data has been undertaken in order to establish the nature of the relationships between numbers and SCG volume (V(scg)). For SCGs (five per species), the allometric relationship for neuron number (N) is N=35,067xV (scg) (0.781) and that for synapses is N=20,095,000xV (scg) (1.328) , the former being a good predictor and the latter a poor predictor of synapse number. Our findings thus reveal the nature of SCG growth in terms of its main ingredients (neurons, neuropil, blood vessels) and show that larger mammals have SCG neurons exhibiting more complex arborizations and greater numbers of axo-dendritic synapses.
    Cell and Tissue Research 08/2010; 341(2):223-237. · 3.68 Impact Factor
  • A Rainey, T M Mayhew
    [Show abstract] [Hide abstract]
    ABSTRACT: The intrauterine environment has an important influence on placental development. In pre-eclampsia (PE) and intrauterine growth restriction (IUGR), early remodelling of spiral arteries has repercussions for uteroplacental blood flow. The IUGR placenta exhibits compromised growth of villous trees, a smaller intervillous space and a lower diffusive conductance. Here, we test whether or not term placentas associated with PE or IUGR also exhibit changes in structural quantities (notably, sizes and numbers of intervillous pores and villous domains) pertinent to uteroplacental haemodynamics. Paraffin wax sections were sampled at random locations and orientations and structural quantities obtained by combining design-based stereological estimates of total and star volumes with model-based estimates of pore hydraulic diameters. Total volumes of intervillous pores and villi were estimated by point counting, total villous surface by intersection counting and star volumes by measuring point-sampled intercept lengths. Other quantities were derived secondarily and group estimates compared by two-way analysis of variance. We found significant main effects of IUGR but no main or interaction effects involving PE. In IUGR, there were fewer intervillous pores and these had larger hydraulic diameters. IUGR also produced fewer villous domains but these were constant in star volume and villi had a constant mean diameter and volume fraction. We concluded that IUGR compromises placental development by producing intervillous pores and villous trees different in size and shape from those in control and PE pregnancies. Calculations suggest that Darcian conductances in the intervillous space improve in IUGR but, in reality, placental performance is compromised by other physiological and structural constraints including the known decline in diffusive conductances.
    Placenta 05/2010; 31(7):602-6. · 3.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Intensive fish production worldwide has increased the risk of infectious diseases. However, before any infection can be established, pathogens must penetrate the primary barrier. In fish, the three major routes of infection are the skin, gills and gastrointestinal (GI) tract. The GI tract is essentially a muscular tube lined by a mucous membrane of columnar epithelial cells that exhibit a regional variation in structure and function. In the last two decades, our understanding of the endocytosis and translocation of bacteria across this mucosa, and the sorts of cell damage caused by pathogenic bacteria, has increased. Electron microscopy has made a valuable contribution to this knowledge. In the fish-farming industry, severe economic losses are caused by furunculosis (agent, Aeromonas salmonicida spp. salmonicida) and vibriosis [agent, Vibrio (Listonella) anguillarum]. This article provides an overview of the GI tract of fish from an electron microscopical perspective focusing on cellular damage (specific attack on tight junctions and desmosomes) caused by pathogenic bacteria, and interactions between the ‘good’ intestinal bacteria [e.g. lactic acid bacteria (LAB)] and pathogens. Using different in vitro methods, several studies have demonstrated that co-incubation of Atlantic salmon (Salmo salar L.) foregut (proximal intestine) with LAB and pathogens can have beneficial effects, the cell damage caused by the pathogens being prevented, to some extent, by the LAB. However, there is uncertainty over whether or not similar effects are observed in other species such as Atlantic cod (Gadus morhua L.). When discussing cellular damage in the GI tract of fish caused by pathogenic bacteria, several important questions arise including: (1) Do different pathogenic bacteria use different mechanisms to infect the gut? (2) Does the gradual development of the GI tract from larva to adult affect infection? (3) Are there different infection patterns between different fish species? The present article addresses these and other questions.
    Aquaculture Research 02/2010; 41(4):451 - 467. · 1.42 Impact Factor

Publication Stats

5k Citations
611.05 Total Impact Points

Institutions

  • 1991–2014
    • University of Nottingham
      • • School of Life Sciences
      • • School of Biomedical Sciences
      • • Centre for Mathematical Medicine and Biology
      • • Centre for Sports Medicine
      Nottigham, England, United Kingdom
  • 2012
    • University of São Paulo
      • Faculty of Medicine (FM)
      São Paulo, Estado de Sao Paulo, Brazil
  • 2004–2011
    • University of Cambridge
      • Department of Physiology, Development and Neuroscience
      Cambridge, ENG, United Kingdom
  • 2009
    • Nottingham University Hospitals NHS Trust
      Nottigham, England, United Kingdom
    • Justus-Liebig-Universität Gießen
      • Institut für Veterinär-Anatomie, -Histologie und -Embryologie
      Gießen, Hesse, Germany
  • 2008
    • The University of Manchester
      • Mental Health Research Group
      Manchester, ENG, United Kingdom
  • 2004–2007
    • Norwegian School of Veterinary Science
      • Department of Food Safety and Infection Biology
      Oslo, Oslo, Norway
  • 2001–2002
    • The Norwegian College of Fishery Science
      Tromsø, Troms, Norway
  • 2000
    • The University of Edinburgh
      • Medical Genetics Unit
      Edinburgh, SCT, United Kingdom
  • 1998
    • Universitetet i Tromsø
      • Norwegian College of Fishery Science
      Tromsø, Troms, Norway
  • 1993–1996
    • Sokoine University of Agriculture (SUA)
      • Department of Veterinary Pathology
      Murogoro, Morogoro Region, Tanzania
  • 1981–1995
    • University of Aberdeen
      • Obstetrics and Gynaecology
      Aberdeen, Scotland, United Kingdom
  • 1992
    • University of Queensland
      Brisbane, Queensland, Australia
  • 1972–1982
    • The University of Sheffield
      • School of Clinical Dentistry
      Sheffield, England, United Kingdom