Biomedical subjects

Terry M Mayhew

Publications and source records attributed to Terry M Mayhew.

9 recordsLinked to original sources

PubMed2006

Allometric studies on growth and development of the human placenta: growth of tissue compartments and diffusive conductances in relation to placental volume and fetal mass.

Correlations between placental size and fetal mass during gestation fail to account for changes in composition that accompany placental growth and maturation. This study uses stereological data on the sizes of different tissue compartments in human placentas from 10 weeks of gestation to term and relates them to placental volume and to fetal mass by means of allometric analysis. In addition, tissue dimensions are used to calculate a physiological transport measure (diffusive conductance) for the villous membrane. Histological sections randomly sampled from placentas and analysed stereologically provided estimates of structural quantities (volumes, exchange surface areas, lengths, numbers of nuclei, diffusion distances). These data were combined with a physicochemical quantity (Krogh's diffusion coefficient) in order to estimate oxygen diffusive conductances for the villous membrane and its two components (trophoblast and stroma). Allometric relationships between these quantities and placental volume or fetal mass were obtained by linear regression analyses after log-transformation. Placental tissues had different growth trajectories: most grew more rapidly than placental volume and all grew more slowly than fetal mass. Diffusion distances were inversely related to placental and fetal size. Differential growth impacted on diffusive conductances, which, again, did not improve commensurately with placental volume but did match exactly growth of the fetus. Findings show that successful integration between supply and demand can be achieved by differential tissue growth. Allometric analysis of results from recent studies on the murine placenta suggest further that diffusive conductances may also be matched to fetal mass during gestation and to fetal mass at term across species.

Biological Transport↗

PubMed2005

Induction of intrauterine growth restriction by reducing placental vascular growth with the angioinhibin TNP-470.

The placenta is a specialized vascular interface between the maternal and fetal circulations that increases in size to accommodate the nutritional and metabolic demands of the growing fetus. Vascular proliferation and expansion are critical components of placental development and, consequently, interference with vascular growth has the potential to severely restrict concurrent development of both the placenta and fetus. In this study, we describe the effects of an antiangiogenic agent, TNP-470, on placental vascular development and the induction of a form of intrauterine growth restriction (IUGR) in mice. Administration of TNP-470 to dams in the second half of pregnancy resulted in a smaller maternal weight gain accompanied by decreased placental and fetal sizes in comparison with control animals. Total numbers of fetuses per litter were not affected significantly. Stereological analysis of placentas revealed no changes in the combined lengths of vessels. However, the mean cross-sectional areas of maternal and fetal vessels in the labyrinth of TNP-470-treated mice were reduced at Embryonic Day 13.5 (E13.5) but not at E18.5. Further analysis showed reduced placental endothelial proliferation at E13.5 and E18.5 in TNP-470-treated animals. No other structural or morphometric differences in placentas were detected between TNP-470-treated and control mice at E18.5. This study provides conclusive evidence that administration of TNP-470 interferes with placental vascular proliferation and vessel caliber and results in a reproducible model of IUGR.

Angiogenesis Inhibitors↗

PubMed2005

Remodeling of myometrial radial arteries in preeclampsia.

OBJECTIVE: This study was undertaken to test for structural differences between myometrial radial arteries isolated from women having normal pregnancies and pregnancies complicated by preeclampsia and intrauterine growth restriction. STUDY DESIGN: Pressure myography was used to study myometrial radial arteries obtained at cesarean section. With the use of a transilluminating system, lumen diameter, wall thickness, wall/lumen ratio, distensibility and stress-strain relationship were studied through a range of pressures. Arteries were then fixed in glutaraldehyde, embedded in resin, cross-sectioned, and studied in greater detail by light and electron microscopy. RESULTS: Pressure myography showed that arteries from women with preeclampsia had a reduced lumen diameter, thicker wall, and greater wall/lumen ratio compared with vessels isolated from women with normal pregnancy. Light microscopy indicated an identical media content remodeled around a smaller lumen. Electron microscopy indicated enlarged extracellular spaces in the media but no change in myocyte profile size or number. There was no clear evidence of structural changes in myometrial radial arteries isolated from women with intrauterine growth restriction compared with normal pregnancy. No differences in vessel distensibility or stress-strain relationships were detected in complicated pregnancies. CONCLUSION: The changes observed in myometrial radial arteries isolated from women with preeclampsia are due to inward eutrophic remodeling. Alterations in these vessels may contribute to increased uterine vascular resistance in preeclampsia.

Adult↗

PubMed2005

Estrogenic induction of spermatogenesis in the hypogonadal (hpg) mouse: role of androgens.

Testicular development is arrested in the hypogonadal (hpg) mouse due to a congenital deficiency of hypothalamic gonadotropin-releasing hormone synthesis. Previous studies have demonstrated that chronic treatment of these mice with estradiol induces testicular maturation and qualitatively normal spermatogenesis, but it is not known whether these are direct effects via estrogen receptors expressed in the testis, or indirect actions via the pituitary gland. The aim of the current studies was to determine whether the actions of estradiol require the presence of androgens. Sensitive assays revealed that chronic estradiol treatment produced time-dependent increases in pituitary FSH production but no increases in pituitary LH or testicular testosterone content could be detected. As a functional test of androgen dependence, hpg mice were treated for 70 days with estradiol plus Casodex (bicalutamide), an androgen receptor antagonist. Casodex treatment markedly attenuated both the estradiol-induced increase in testicular weight and the proliferation of the seminiferous epithelium, as revealed by morphometric analysis. However, it did not affect the estradiol-induced increase in pituitary FSH content, nor did it affect estradiol-induced increases in the weight of the seminal vesicles and epididymides. We conclude that increased FSH production is not sufficient to explain the increase in testicular development induced by estradiol in hpg mice; there is a requirement for functional androgen receptors for induction of testicular growth.

Androgen Antagonists↗

PubMed2004

Damaging effect of the fish pathogen Aeromonas salmonicida ssp. salmonicida on intestinal enterocytes of Atlantic salmon (Salmo salar L.).

In fish, bacterial pathogens can enter the host by one or more of three different routes: (a) skin, (b) gills and (c) gastrointestinal tract. Bacteria can cross the gastrointestinal lining in three different ways. In undamaged tissue, bacteria can translocate by transcellular or paracellular routes. Alternatively, bacteria can damage the intestinal lining with extracellular enzymes or toxins before entering. Using an in vitro (Ussing chamber) model, this paper describes intestinal cell damage in Atlantic salmon (Salmo salar L.) caused by the fish pathogen Aeromonas salmonicida ssp. salmonicida, the causative agent of furunculosis. The in vitro method clearly demonstrated substantial detachment of enterocytes from anterior region of the intestine (foregut) upon exposure to the pathogen. In the hindgut (posterior part of the intestine), little detachment was observed but cellular damage involved microvilli, desmosomes and tight junctions. Based on these findings, we suggest that A. salmonicida may obtain entry to the fish by seriously damaging the intestinal lining. Translocation of bacteria through the foregut (rather than the hindgut) is a more likely infection route for A. salmonicida infections in Atlantic salmon.

Aeromonas salmonicida↗

PubMed2004

Applications of an efficient method for comparing immunogold labelling patterns in the same sets of compartments in different groups of cells.

Quantitative immunoelectron microscopy often involves determining the distributions of gold label in different intracellular compartments and then drawing comparisons between compartments in the same sample of cells or between experimental groups of cells. In the case of within-group comparisons, recent developments in the estimation of relative labelling index and labelling density make it possible to test whether or not particular compartments are preferentially labelled. These methods are ideally suited to analysing gold label restricted to volume (organelle) or surface (membrane) compartments but may be modified to analyse label localised in mixtures of both. Here, a simple and efficient approach to drawing between-group comparisons for label associated with organelles and/or membranes is presented. The method relies on multistage random sampling of specimens (via blocks and microscopic fields) followed by simply counting gold particles associated with different compartments. The distributions of raw gold counts in different groups are then compared by contingency table analysis with statistical degrees of freedom for chi-squared values being determined by the number of compartments and the number of experimental groups of cells. Compartmental chi-squared values making substantial contributions to the total chi-squared values then identify where the main between-group differences reside. The method requires no information about compartment size (for example, organelle profile area or membrane trace length) and does not even depend critically on standardising between-group magnification. Its application is illustrated using datasets from immunolabelling studies designed to localise the KDEL receptor, phosphatidyl-inositol 4,5-bisphosphate, GLUT4 and rab4 at the electron microscopic level.

Glucose Transporter Type 4↗

PubMed2004

A rapid method for assessing the distribution of gold labeling on thin sections.

Particulate gold labeling on ultrathin sections is in widespread use for antigen localization at the EM level. To extend the usefulness of gold labeling technology, we are evaluating different methods for sampling and estimating quantities of gold labeling. Here we present a simple, rapid, and unbiased method for assessing the relative pool sizes of immunogold labeling distributed over different cell compartments. The method uses a sampling approach developed for stereology in which a regular array of microscopic fields or linear scans is positioned randomly on labeled sections. From these readouts, gold particles are counted and assigned to identifiable cell structures to construct a gold labeling frequency distribution of those labeled compartments. Here we use ultrathin cryosections labeled for a range of different proteins and for a signaling lipid. We show by scanning labeled sections at the electron microscope that counting 100-200 particles on each of two grids is sufficient to obtain a reproducible and rapid assessment of the pattern of labeling proportions over 10-16 compartments. If more precise estimates of labeling proportions over individual compartments are required (e.g., to achieve coefficients of error of 10-20%), then 100-200 particles need to be counted over each compartment of interest.

Animals↗

PubMed2002

Fetoplacental angiogenesis during gestation is biphasic, longitudinal and occurs by proliferation and remodelling of vascular endothelial cells.

Villous development and maturation depend on fetoplacental angiogenesis but detailed baseline quantitative data on underlying structural events are lacking. The present aim was to analyse temporospatial patterns of villous and fetal vascular growth using microscopical sections of placentae at different periods of gestation. The emphasis is on acquiring absolute rather than relative data. Random tissue samples collected at 10-41 weeks of gestation were processed for stereological analyses. Growth strategies in 'stem', 'intermediate' and 'terminal' villi (classified according to villous diameter and nature of fetal vessels) were evaluated in terms of total volumes, lengths and mean cross-sectional areas. Total volume, total and relative length, mean cross-sectional area and shape, vascular endothelial cell number and mean cell size (squame surface area) were used to examine capillary growth. Volumes of 'intermediate' and 'terminal' villi increased significantly due to elongation and thinning. Villous maturation involved differential growth of capillaries which grew linearly without changes in mean cross-sectional area. Longitudinal growth was due to endothelial cell proliferation and increases in mean cell area. Events were characterized by a common inflection point at about mid-gestation. Usually, an early slow growth phase was followed by one of faster growth but capillary : villus length ratios and capillary shape factors tended to peak at mid-gestation. Findings confirm that angiogenesis is linked to villous growth and maturation, and is biphasic with dramatic changes in vascular content and arrangement occurring around mid-gestation. Capillary growth occurs preferentially and is solely by increase in total length driven by continuous proliferation and, later, by endothelial cell remodelling. Though providing no evidence for branching versus non-branching angiogenesis, these observations are consistent with the paradigm that fetoplacental angiogenesis occurs in two phases, the switch being associated with changes in uteroplacental oxygen tensions, local growth factor receptors and their ligands.

Capillaries↗

PubMedDate not supplied

Changes in fetal capillaries during preplacental hypoxia: growth, shape remodelling and villous capillarization in placentae from high-altitude pregnancies.

Patterns of fetoplacental angiogenesis and villous growth vary in pregnancies complicated by different forms of fetal hypoxia. This study uses stereological estimators to examine absolute and relative dimensions of villi and fetal capillaries in cases of preplacental hypoxia due to pregnancy at high altitude. Placental samples were drawn from well-defined subjects in different ethnic groups born, raised and completing term pregnancies at low (500 m) and high altitude (3600 m above sea level). Volumes, surfaces and lengths were used to monitor the nett growth of villi and capillaries. Indices of villous capillarization comprised volume, surface and length densities and capillary:villus surface and length ratios. Villus/capillary 'calibre' and shape were quantified using cross-sectional areas, perimeters and shape coefficients (perimeter(2)/area). Group comparisons were drawn by two-way analyses of variance with altitude and ethnicity as the main factors. Volumes, surfaces and lengths of villi, and volumes of capillaries, were reduced at high altitude. Capillary volume declined primarily by formation of narrower microvessels which were more irregular in outline. There were no differences in capillary surface area or length. Cross-sectional sizes and shapes of villi were unaltered. Differences in villous capillarization were confined to higher surface and length densities. Ethnic differences in villous length, capillary length and cross-sectional area tended to favour native groups who are pre-adapted to life at high altitude. Results show that high-altitude pregnancy is not accompanied by increased angiogenesis but may involve enhanced villous capillarization and vascular shape remodelling. Comparisons are drawn with changes seen in maternal anaemia. It is concluded that absolute and relative measures of villous and capillary growth are required lest misinterpretations are introduced by equating hypercapillarization with enhanced angiogenesis or the pattern of capillary branching. The importance of controlling for various potential confounders is also emphasized.

Adaptation, Physiological↗