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T M Mayhew

Publications and source records attributed to T M Mayhew.

At least 109 records · Page 6Linked to original sources
PubMed1987

Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. II. Glomerular basement membrane thickness.

Stereological studies were performed on renal glomeruli from control rats, untreated streptozotocin-diabetic rats and diabetics treated by subcutaneous infusion of insulin for 16 weeks. Estimates of glomerular basement membrane thickness were obtained by dividing membrane volume by membrane surface area. In addition, arithmetic and harmonic mean thicknesses were calculated from orthogonal intercept lengths, and used to provide information on the variability of basement membrane thickness. In untreated diabetics, both arithmetic and harmonic mean thicknesses were significantly greater than values found in control animals. The thickening of the basement membrane appeared to be generalized rather than markedly focal. All thickness variables were normalized by insulin infusion therapy. These findings underline the importance of good glycaemic control and early intervention in experimental diabetes and one of its main complications.

Animals↗
PubMed1987

Quantitative ultrastructural study on the responses of microvilli along the small bowel to fasting.

Stereological methods were employed to investigate the effects of fasting on the numbers and sizes of microvilli in three regions of the rat small bowel. Duodenal, jejunal and ileal segments displayed differences in microvillous amplification factors, absolute surface areas and mean lengths but no significant differences in the mean diameters or packing densities of microvilli. Fasting had no effects on amplification factors, mean diameters or numbers. However, fasted animals possessed significantly less microvillous surface area (0.9 versus 1.2 m2) due to a reduction in total villous surface area and, probably, to decreases in the average lengths of microvilli. In no instance was any significant interaction effect demonstrable. Thus, fasting influenced all regions of the small intestine in similar fashion. The paper concludes a study into the effects of fasting on villi and microvilli along the small bowel.

Animals↗
PubMed1987

The volumetric composition of human term placentae: altitudinal, ethnic and sex differences in Bolivia.

Point counting volumetry has been used to decide whether or not altitudinal, ethnic and sex differences in birth weight in Bolivia are accompanied by changes in placental composition. Sixty eight placentae from healthy, term pregnancies were sampled from populations of Amerindian and non-Indian women living in Santa Cruz (400 m) and La Paz (3600 m). Altitudinal reductions in birth weight were not accompanied by significant alterations in placental weight yet highland placentae were substantially different in histological composition. On average, the highland placenta had a more voluminous intervillous space but reduced volumes of villi, juxtavillous fibrin and non-parenchyma. Whilst Amerindian newborn were heavier, placental weights were similar in both ethnic groups. However, the Amerindian placenta tended to possess more trophoblast and more villous stroma than its non-Indian counterpart. No sex differences were detected save for an interaction effect on fibrin which involved altitude, ethnic group and sex. Findings are discussed in the context of known morphometric and physiological differences between placentae in different experimental groups, notably in other types of pregnancy associated with reduced fetal growth.

Altitude↗
PubMed1985

The problem of ambiguous profiles of microvilli between apposed cell surfaces: a stereological solution.

When interdigitating microvilli projecting from apposed cell surfaces are sectioned randomly, it becomes impossible to specify to which of the two parent surfaces an individual microvillous profile belongs. Because of this image ambiguity, direct estimation of the ratio of microvillous surface areas by intersection counting cannot be performed. A stereological solution to this problem is proposed. It relies on counts of the numbers of bases of microvilli identified on each reference (parent) surface.

Animals↗
PubMed1985

Crypts, villi and microvilli in the small intestine of the rat. A stereological study of their variability within and between animals.

Small intestines from normal adult rats were quantified by optical and electron microscopy using stereological principles devised for the purpose. Five segments per bowel were examined. Baseline data characterising villi, microvilli and crypts of Lieberkühn were used to study differences between segments and between animals. Intestines fixed by in situ perfusion had, on average, 100 cm2 of primary mucosa. This basic surface was amplified to 500 cm2 by villi and to 1 m2 by the microvilli of enterocytes. Villous and microvillous surface areas may scale to body weight in the same way as metabolic requirements. Proximodistal gradients in mucosal architecture existed for the volumes and surface areas of villi and for the numbers, lengths, diameters and surface areas of microvilli. Most variables were higher proximally and declined towards the terminal ileum. The volume of crypts stayed constant throughout the entire intestine and ratios between villous dimensions (volumes and surface areas) and crypt volume did not vary between animals. Findings are discussed in the context of regional differences in bowel function and of their relevance to studies of epithelial kinetics.

Animals↗
PubMed1984

Geometric model of the rat intestinal mucosa for stereological evaluation of villus amplification factors.

This study was prompted by a desire to compare villus amplification factors at various sites along the small intestine of the laboratory rat. The paper describes a precise and efficient stereological method for achieving this objective. The method relies on conventional intersection counts performed exclusively on transverse sections. Analyses are based on six adult rats. Pieces of small bowel fixed by in situ perfusion were taken from proximal, middle and distal regions. Intersection counts on villus and primary mucosal surfaces were performed on transverse and longitudinal sections through the same regions. These counts revealed that intestinal architecture can be reasonably approximated by the simple geometric model of an isotropic villus surface on an anisotropic (cylindrical) primary mucosal surface. As a result, intersection counts may be confined to transverse sections (to reduce sampling variance) and the appropriate ratio estimator multiplied by the numerical coefficient 4/pi (to obtain an estimate of surface amplification due to villi).

Animals↗
PubMed1984

Sampling schemes for estimating nerve fibre size. I. Methods for nerve trunks of mixed fascicularity.

Using the tibial nerves of diabetic rats, alternative sampling schemes have been compared for estimating the sizes of fibres in nerve trunks of mixed fascicularity. The merits of each scheme were evaluated by comparing their reliability, precision, cost in time, and efficiency with 'absolute' values obtained by first measuring every fibre. The external diameter of all myelinated fibres was measured in each of six nerves (c. 2900 fibres/nerve). Total measurement time was about 29 hours. All sampling schemes produced group means within +/-4% of the absolute value of 5.52 micron. The most efficient schemes were those in which only 6% of all fibres were selected for measurement. For these the measurement time was 2 hours or less. Results are discussed in the general context of measurement of the sizes of nerve fibres. It is concluded that future studies should place more emphasis on sampling fewer fibres from more animals rather than on measuring all fibres very precisely. These considerations are likely to be of special concern to those wanting to analyse specimens with large fibre complements and those screening large numbers of specimens.

Animals↗
PubMed1984

Sampling schemes for estimating nerve fibre size. II. Methods for unifascicular nerve trunks.

The total number of myelinated fibres in four unifascicular tibial nerves from diabetic rats has been counted and measured in order to assess the merits of various schemes for estimating group mean fibre diameter. The average nerve trunk contained some 2960 fibres which were measured in just under five hours. With different sampling designs, the average measurement time per nerve was reduced to between 17 and 69 minutes, with little consequent loss of reliability or precision of estimated mean fibre size. The most efficient schemes were those taking systematic samples of squares or sectors. A modification of a method relying on complete strips across two diameters of each nerve was the least efficient sampling approach. It had the additional disadvantage of introducing systematic errors which could affect the accuracy of measurements made on nerve trunks with heterogeneous spatial distributions of fibre size and number. This paper completes an investigation into random sampling errors influencing morphometric estimates of fibre size based on uni- or multifascicular nerve trunks.

Animals↗
PubMed1984

Structure-function correlation in the human placenta: the morphometric diffusing capacity for oxygen at full term.

A combination of stereology and physiology is used to estimate the morphometric diffusing capacity for oxygen of the normal human placenta at term. The morphometric diffusing capacity is found to be higher than published values determined by physiological methods. The most likely explanation for this discrepancy is that physiological values are too low because of the effects of shunts, placental oxygen consumption and uneven diffusion:perfusion ratios. Despite the discrepancy, morphometry of histological sections offers a valuable and practicable alternative for comparing the functional potential of the placenta in different species, during normal gestation, disease, experimental treatment and environmental hypoxic stress.

Diffusion↗
PubMed1983

Inter-animal variation and its influence on the overall precision of morphometric estimates based on nested sampling designs.

This paper provides additional experimental evidence that biological variation between individuals is likely to be the major factor influencing the overall precision and efficiency of nested sampling schemes for morphometric analysis of thin sections. Four distinct experimental systems (two based on nervous tissue and two on epithelia) have been investigated. Morphometric estimates were obtained from measurements made on micrographs generated by sampling tissues at several levels. Sources of sampling variation were isolated so that the contributions to overall variance made by inter-animal differences could be evaluated. In each case, biological variation was the cardinal component of total observed variance between animals. Relative contributions ranged from 53% to 78%. Examining more animals would be the most efficient way of reducing the variance of the group mean in these sampling designs.

Animals↗
PubMed1982

Towards economy of effort in quantitative ultrastructural pathology: efficient sampling schemes for studying experimental carcinogenesis.

Hamster cheek pouch mucosa was painted with DMBA in order to compare samples of epithelium at different pathological stages of carcinogenesis. Stereological methods were applied to ultrathin sections of tissue to estimate one ultrastructural index of change, the surface ratio of lamina densa compared with the overlying plasma membrane of cells in stratum basale. Analysis of variance techniques were then employed to isolate and quantify the contributions which different levels of sampling (animals, tissue blocks, microscopic fields) made to the total observed variation in this surface ratio. Economical sampling schemes for future use were calculated from the sampling variances by taking into account the relative costs at each sampling level. Though illustrated by means of the hamster cheek pouch-DMBA model, our results are pertinent to many other experimental models for quantitative histopathology.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Stereological methods for quantifying cell surface specializations in epithelia, including a concept for counting desmosomes and hemidesmosomes.

We present stereological procedures for morphometric evaluation of intercellular junctions appearing in ultrathin sections of epithelia. A model representing desmosomes and hemidesmosomes as flat, circular discs differentiated within the plasma membrane of epithelial cells forms a basis for estimating number per unit volume of tissue or per unit area of cell surface. Methods for estimating relative surfaces are also provided. Consideration is given to problems of tissue sampling, varying feature size and finite section thickness. The procedures are improvements over earlier estimates of number per unit area of section or per unit length of membrane. Worked examples of calculations are included and methods are illustrated further by reference to quantitative studies of hamster cheek pouch epithelium during experimental carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Ultrastructural morphometry of blastogenesis. II. Stimulated lymphocytes, the progeny of blast cells induced in vivo with DNCB.

As a companion to an earlier study, the morphometric attributes of stimulated (blast-derived) lymphocytes in mouse axillary lymph nodes have been established using stereological and autoradiographic methods. Blast transformation was induced in vivo with dinitrochlorobenzene (DNCB) and stimulated cells were labelled with tritiated thymidine. Random samples of cells were taken for light and electron microscopic morphometry. In comparison to the unstimulated lymphocyte, the stimulated cell increased in size and possessed a greater plasma membrane surface area. Increase in cell size was the result of increases in the volumes of all measured subcellular compartments both in the nucleus and the cytoplasm. Heterogeneity of the stimulated cell population precludes firm conclusions regarding the significance of all these ultrastructural changes, though alterations in cell surface are discussed in the context of known biochemical differences accompanying blastogenesis.

Animals↗
PubMed1981

On the relative efficiencies of alternative ratio estimators for morphometric analysis of cell membrane surface features.

For morphometric analysis of desmosomes, synapses and other membrane surface features, estimating component densities on a reference surface (the membrane with which they are associated) often provides a useful practical alternative to estimating densities in a reference volume (the tissue in which they are enclosed). The present report assesses the relative efficiencies of these two approaches. In particular, the efficiencies of stereological estimators for component numerical density on a surface (NS) and in a volume (NV) are compared, together with those for the surface densities SS and SV. For this purpose, a morphometric model developed for characterizing desmosomes in human forearm skin was quantified by point and intersection counting. The efficiencies of the alternative ratio estimators were evaluated by comparing their coefficients of variation obtained on samples of equivalent size and having a similar overall analysis time. Various types of bias influencing the results are also discussed. The results demonstrate that estimators of component densities on a surface are superior to those of densities in a volume when studying epidermal desmosomes. For a given size of sample they offer a smaller coefficient of variation. In other words, they are more efficient. They may be even more advantageous in other experimental situations.

Cell Membrane↗
PubMed1980

Ultrastructural morphometry of isolated cells: methods, models and applications.

Isolated cells constitute a favourable experimental model for the pathologist interested in ultrastructural morphometry. A particular advantage is that the same sampling regime may be appropriate for both normal and pathologically-altered material. Often this is not the case with other model systems. This report reviews alternative methodologies for analysing isolated cells, including free cells and dissociated cells in culture. We begin by attempting to define problems of more general concern: preparative techniques, methods of sampling, selection of stereological parameters and possible sources of error. A generalised morphometric model for isolated cells is followed by descriptions of models devised for specific cell types, notably mononuclear phagocytes and cells of the lymphocyte family. Typical results obtained by stereological analyses of these models are presented.

Animals↗