PubMed Health⌕ Search

Biomedical subjects

D R Garrod

Publications and source records attributed to D R Garrod.

14 recordsLinked to original sources
PubMed1992

The molecular biology of desmosomes and hemidesmosomes: "what's in a name"?

Desmosomes are junctions involved in intercellular adhesion of epithelial cells and hemidesmosomes are junctions involved in adhesion of epithelia to basement membranes. Both are characterised at the ultrastructural level by dense cytoplasmic plaques which are linked to the intermediate filament cytoskeleton of the cells. The plaques strongly resemble each other suggesting a relationship between the two kinds of junctions, as implied by their names. Recent characterisation of the molecular components of the junctions shows they are, in fact, quite unrelated implying that structural similarity is fortuitous. The molecular biology raises many fascinating problems relating to their structure and function.

Animals↗
PubMed1991

Cell adhesion in Hailey-Hailey disease and Darier's disease: immunocytological and explant-tissue-culture studies.

The pathogenesis of Hailey-Hailey disease and Darier's disease was investigated using immunocytological and explant-tissue-culture techniques. There was breakdown of the intercellular adhesions between keratinocytes in explants from clinically uninvolved skin of patients with Hailey-Hailey disease or Darier's disease. The major desmosomal components were present in the cultures and were expressed in a punctate peripheral pattern at cell-cell contact sites, but there was diffuse staining of acantholytic cells. Plasminogen, which is expressed by basal keratinocytes in normal skin, was detected in association with suprabasal acantholytic cells in skin biopsies from these diseases. Plasminogen was reversibly displaced from the cells by 6-aminohexanoic acid, suggesting that binding is mediated by a reaction with the lysine receptor on the plasminogen molecule. Plasminogen was also detected in separating cells in explant cultures and there was cytoplasmic expression of the plasminogen activator urokinase by these cells. These abnormalities are not unique to either disease and do not account for the phenotypic differences between Darier's disease and Hailey-Hailey disease, but plasmin generation may have a role in perpetuating cell separation.

Adult↗
PubMed1979

A ligand-receptor model for the cohesive behaviour of Dictyostelium discoideum axenic cells.

Axenically grown cells of D. discoideum Ax-2 harvested in the log phase of growth, cohere rapidly when shaken in phosphate buffer. After 3.5 days in the stationary phase of growth, cells become completely non-cohesive. Although they do not stick to each other, stationary phase cells do stick to both log phase cells and aggregation-competent cells. The cohesion of stationary phase cells with these other 2 cell types is inhibited by both EDTA and the low-molecular-weight factor which we have previously demonstrated in stationary-phase growth medium. There is a decline in the sensitivity of slime mould cell cohesion to the low-molecular-weight inhibitory factor as the cells become aggregation-competent. This effect parallels the developmentally-regulated decline in sensitivity to EDTA. The low-molecular-weight inhibitor is not a chelating agent, however. The effect of the inhibitor seems to be specifically against contact sites-B mediated cohesion. We suggest that the simplest cohesive mechanism which can explain our results, is that the EDTA-sensitive cohesion of log phase cells could be dependent on a ligand-receptor system.

Adhesiveness↗
PubMed1979

The sorting out of embryonic cells in monolayer, the differential adhesion hypothesis and the non-specificity of cell adhesion.

It has been reported previously that sorting out of chick embryonic liver parenchyma and limb bud mesenchymal cells would take place in monolayer culture. The distribution of cell types obtained (liver formed the internal, discontinuous phase) was interpreted in terms of the differential adhesion hypothesis. It was suggested that, in monolayer, liver cells were more cohesive than limb bud cells. In this paper we set out to extend the previous observations with 2 particular questions in mind: (i) Is sorting out in monolayer a general phenomenon occurring between a wider range of cell types? (ii) Can evidence be provided for or against the interpretation of results in terms of the differential adhesion hypothesis? Sorting-out experiments were conducted on circular hydrophilic islands, on an otherwise hydrophobic substratum. Under these conditions, sorting-out in monolayer was obtained with binary combinations of 4 chick embryonic tissue types: liver parenchyma, limb bud mesenchyme, pigmented epithelium of the eye and corneal epithelium. With every combination but one, the cells of one type surrounded the cells of the other type, generating what we have called a 'circle-within-a-circle' configuration. With the remaining combination, liver parenchyma and corneal epithelium, only localized sorting was obtained. The 'circle-within-a-circle' configuration is consistent with an interpretation in terms of the differential adhesion hypothesis, according to which the distribution of cells is determined by the relative strengths of cohesions between their lateral surfaces. In direct support of this is the finding from plating the different cell types at sub-confluent density on hydrophilic substrata that limb bud is the cell tye having the weakest lateral cohesion in monolayer. Limb bud surrounded the other 3 tissues on hydrophilic island. A hierachy of lateral cohesiveness between the 4 cell types has been constructed. It is unlikely that the results can be explained in terms of specific cohesion. When plated together at subconfluent density, the 3 epithelial cell types aggregate together to form mixed monolayered islands, suggesting that they share common adhesive mechanisms.

Animals↗
PubMed1979

Effect of isolated plasma membranes on cell cohesion in the cellular slime mould.

The effects of isolated plasma membranes on cohesion of Dictyostelium discoideum Ax-2 cells have been studied. Membranes isolated from cells in the log phase of growth gave complete inhibition of log-phase cell cohesion. This effect was specific for the cohesion log-phase cells mediated by contact sites B, since the cohesion of aggregation-competent cells which have acquired contact sites A was only partially inhibited by log-phase plasma membranes. Membranes isolated from stationary phase cells gave partial inhibition of log-phase cell cohesion, while membranes from aggregation-competent cells gave complete inhibition of log-phase cell cohesion but at much higher concentration than log membranes. Treatment of log-phase cells with cycloheximide for 8 h rendered them completely non-cohesive. Membranes from cycloheximide-treated cells had no effect on log-phase cell cohesion. Log-phase membranes gave complete inhibition of cohesion of 4 slime mould species. The results are discussed in terms of our ligand-receptor model of log-phase cell cohesion.

Cell Cycle↗
PubMed1978

Mutual cohesion and cell sorting-out among four species of cellular slime moulds.

Interspecific cell cohesion among 4 species of cellular slime moulds, Dictyostelium discoideum, D. mucoroides, D. purpureum and Polysphondylium violaceum has been studied. Binary mixtures of aggregation-stage cells of the 4 species were shaken in suspension, one species of each pair being labelled with [3H]thymidine. Cell aggregates were sampled at intervals over 24 h and their composition examined by autoradiography. The following results were obtained: (i) Cells of each species were capable of cohesion with those of the other 3 species. (ii) In general cells of both species in any mixture were present in aggregates after 1 h, but were not localized according to species. (iii) Within 8-h aggregates cells of different species were regionally localized, i.e. sorting-out appeared to have taken place. (iv) 24-h aggregates were more varied: in mixtures of Dictyostelium species, the different species were localized within the aggregates; in mixtures of Dictyostelium species with Polsphondylium, there was a tendency for cells of the different species to become segregated into completely separate aggregates. The significance of these results in relation to both previous descriptive work and recent biochemical studies on the mechanism of slime mould cell cohesion is discussed.

Adhesiveness↗
PubMed1977

An inhibitor of cell cohesion from axenically grown cells of the slime mould, Dictyostelium discoideum.

Medium from a stationary phase culture of axenically grown D. discoideum cells contains an inhibitor of cohesion of log phase cells. The inhibitor is a heat-stable, low molecular weight substance. Its biological effects include inhibition of cohesion of aggregation-competent cells, of cells of other slime mould species, the blocking of development on Millipore filters and a reduction in adhesiveness of slime mould cells to glass. Present evidence suggests that the inhibitor may bind to the cell surface.

Adhesiveness↗
PubMed1975

Observations on the sorting-out of embryonic cells in monolayer culture.

Two problems are raised concerning the movement of cells during tissue-specific sorting-out of chick embryo cells in mixed aggregates. (i) A possible expectation from the hypothesis of 'contact inhibition' is that cells which are entirely surrounded by other cells in monolayer should be held stationary. Cells within solid aggregates, being totally surrounded by others, might also not be expected to move. How is it then that cell movement takes place within solid aggregates during sorting-out? (ii) Are the movements of cells within sorting aggregates 'passive', being driven by adhesive differentials or 'active', being merely guided by such differentials? In order to study these questions, sorting out experiments with chick embryonic limb bud mesenchyme and liver cells were carried out in monolayer culture, permitting direct observation of cell movements. Cell behavior was observed by time-lapse cinematography. Sorting-out of these cells in monolayer began before and continued after the cells had spread to confluency. During sorting, liver cells showed ruffing activity even when they appeared to be totally surrounded by other cells. Both cell types showed contact inhibition as judged by the criterion of monolayering, for they did not move over each other but remained attached to the substratum. Yet the cells in the confluent monolayer were not immobilized. Because of this, we suggest that the observed restraint against overlapping did not result from an inhibition of movement. Several considerations, detailed in the text, suggest that cell movement during sorting-out involve active locomotion. Previous work suggest that sorting-out configurations are determined by the relative intensities of intercellular adhesive strengths, the more cohesive of 2 cell populations tending to adopt the internal position. While limb bud cells form internal islands surrounded by liver cells in solid aggregates, the reverse was found to be the case in these monolayers. This suggests that, in the monolayer, limb bud cohesiveness is depressed relative to liver cell cohesiveness. This is consistent with the observation that the limb bud cells flattened themselves markedly against the substratum, significantly decreasing their area of mutual apposition.

Animals↗
PubMed1975

Cell locomotion within a contact-inhibited monolayer of chick embryonic liver parenchyma cells.

Using time-lapse filming, the relative movement of cells (nuclei) within a contact-inhibited monolayer of chick embryonic liver parenchyma cells has been studied. Two techniques were employed to determine the amount of relative cell movement during a culture period of 6 h. Firstly, the number of neighbours lost or gained by each nucleus was counted. Secondly, the relative distance moved by each nucleus in relation to other nucleus in the monolayer was measured. (The numerical results obtained from these analyses and details of the methods used are given in the text). A considerable amount of relative movement of nuclei within the monolayer was found during this period of culture. Although some gaps were occasionally seen between the cells in the monolayer, it was observed that cells able both to "ruffle" and to translocate when no gap was detectable; i.e. the cells appeared able to move while entirely surrounded by other cells. Because of this, we suggest that the monolayering of these epitheloid cells on a surface may be due to restriction of overlapping between them rather than to inhibition of movement by mutual contact. We argue that the term "contact inhibition of overlapping" relates to this behaviour better than the term "contact inhibition of movement".

Animals↗