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Biomedical subjects

C W Evans

Publications and source records attributed to C W Evans.

At least 19 recordsLinked to original sources
PubMed1992

Cell adhesion and metastasis.

There is no single phenotypic trait whose exclusive expression correlates universally with metastatic behaviour. Nevertheless, several lines of evidence point towards adhesive phenomena as mediating some crucial steps in the malignant spread of particular tumour types. These steps include detachment from the primary, invasion of the ECM including include detachment from the primary, invasion of the ECM including structures such as the basement membrane and organ capsules, and lodgement in the vessels of remote organs. Furthermore, there is evidence that adhesive phenomena can contribute at least in part to the selective patterns of spread shown by a variety of tumour cell types. The molecular dissection of the adhesive events involved in these processes has only just begun. It is clear already, however, that several different determinants are likely to be involved and the clinical application of this knowledge is unlikely to be immediate.

Amino Acid Sequence↗
PubMed1991

A genetic basis for metastasis.

The progression of a normal cell to one that is malignant is characterized by at least four progressive but potentially separable behavioural patterns identifying the immortal, tumorigenic, invasive and metastatic phenotypes. A multitude of steps appear to be involved in both transformation from normality and progression to malignancy as characterized by the acquisition of metastatic behaviour. Consequently, it seems unlikely that a single gene can directly manifest expression of the metastatic phenotype in normal cells unless it can induced pleiotropic effects. Indeed, a single trait uniquely characterizing the metastatic phenotype has never been identified. The possibility of a single gene suppressing the metastatic phenotype seems much greater. One possible candidate for such a gene is nm23, the expression of which correlates with reduced metastatic potential in several tumours including breast cancer in humans. Although the numbers involved are still small, the correlation of nm23 expression with breast cancer outcome offers potential in using this system as a prognostic aid in clinical diagnosis of this disease. Its possible role as an indicator of metastatic potential in other human tumours remains to be evaluated, although current evidence suggests that it is unlikely to be of use in colon cancer. Further significant progress requires molecular dissection of the mode of action of its product.

Humans↗
PubMed1990

Molecular portrait of lens gap junction protein MP70.

A 70-kDa membrane protein (MP70) is a component of the lens fiber gap junctions. Its membrane topology and its N-terminal sequence are similar to those of the connexin family of proteins. Some features of MP70 containing fiber gap junctions are, however, distinct from gap junctions in other mammalian tissues: (i) Lens connexons form crystalline arrays only after cleavage of junctional proteins in vitro. These hexagonal arrays have a periodicity of 13.6 nm which is significantly larger than the 8- 9-nm spacing of liver and heart gap junctions. (ii) Lens fiber gap junctions dissociate in low concentrations of nonionic detergent and this provides an avenue to purify MP70 directly from a membrane mixture. Isolated MP70 in the form of 17 S structures has an appearance consistent with connexon pairs. (iii) The C-terminal half of MP70 is cleaved in situ by a lens endogenous calcium-dependent protease. The processed from MP38 remains in the membrane and is abundant in the central region of the lens. A testable hypothesis for MP70 function is presented.

Connexins↗
PubMed1990

Plasma catecholamines and their physiologic thresholds during the first ten days of life in sheep.

We studied serial plasma catecholamine levels in healthy newborn sheep over the first ten days of life. The results show that plasma norepinephrine values in newborn sheep are 3-4 fold higher, and plasma epinephrine values are two-fold higher than values in term fetal sheep. These elevations are sustained over the first 10 days of life. Cardiovascular (heart rate and blood pressure) and metabolic parameters (glucose and free fatty acids) are also significantly elevated above fetal levels. We performed graded catecholamine infusions in newborn animals and adult ewes to determine the minimum plasma catecholamine concentrations necessary for discernible physiologic effects. In response to step-wise increases in epinephrine or norepinephrine infusion rates, there were immediate increases in blood pressure and other physiologic responses. This pattern was seen in both newborn and adult animals, and differed from previous observations in fetal sheep where log-linear, dose response curves characteristic of a threshold response were seen. These results suggest that during the first two weeks of life plasma catecholamine levels are elevated above the threshold value for physiologic responses. These sustained elevations in circulating catecholamines are important in the maintenance of physiologic homeostasis.

Animals↗
PubMed1989

Neutrophil chemotactic behaviour in patients with early-onset forms of periodontitis (I). Leading front analysis in Boyden chambers.

Despite some reports to the contrary, it is generally assumed that early-onset forms of periodontal disease (including both juvenile and rapidly progressive periodontitis) are associated with a defect in neutrophil (PMN) chemotactic behaviour. Using the Boyden chamber technique and N-formyl-methionyl-leucylphenylalanine (FMLP) to assess locomotion by the leading front method, we have failed to show any evidence for such depressed PMN locomotion. Indeed, when PMN chemotaxis and chemokinesis are considered in response to a range of chemoattractant doses our results indicate significant enhancement of all but random locomotion. When taken together with other studies, our results suggest that PMNs from patients with early-onset periodontitis may show abnormal locomotory behaviour which can either be enhanced or reduced in nature. The extent to which these results reflect in vitro methodology in uncertain and, furthermore, their in vivo significance is unclear.

Adolescent↗
PubMed1989

Neutrophil chemotactic behaviour in patients with early-onset forms of periodontitis (II). Assessment using the under agarose technique.

The locomotory behaviour of peripheral blood neutrophils (PMNs) from patients with juvenile (JP) and rapidly progressive (RPP) forms of early-onset periodontal disease was studied using the under agarose technique and n-formyl-methionyl-leucyl-phenylalanine (FMLP) as the chemotractant. PMNs from experimental patients showed normal random, chemotactic and chemokinetic locomotory behaviour when compared with control subjects. Further investigation of single-cell movements using time-lapse video analysis also failed to show any significant differences in locomotory behaviour between the PMNs of experimental and control individuals. We conclude that differences in technique may account for much of the variation which exists in the literature with respect to PMN locomotion in periodontal disease. In the final analysis, it is difficult to dispute direct observation of moving cells, and using this approach, we have been unable to confirm the presence of any PMN locomotory defect in our series of patients with early-onset periodontal disease.

Adolescent↗
PubMed1989

Depressed helper-to-suppressor T-cell ratios in early-onset forms of periodontal disease.

Helper (CD4+)-to-suppressor (CD8+) T-cell ratios were determined by flow cytometry for 12 patients with early-onset forms of periodontal disease and their appropriate controls. When considered as a group, patients with early-onset periodontal disease showed a markedly depressed CD4+/CD8+ ratio relative to controls (means 0.92 and 1.50 respectively). This difference was significant at the 0.0015% level as determined by the Mann-Whitney test. Separate analysis of patients with either the juvenile or rapidly progressive types of early-onset periodontal disease showed both to have reduced CD4+/CD8+ ratios (means 0.91 and 0.92) relative to their controls (means 1.57 and 1.45) which were both statistically significant (p less than 0.05).

Adolescent↗
PubMed1985

The effects of the B16 malignant melanoma on induced inflammatory responses in host mice: inhibition of macrophage exudation.

C57BL6 mice were injected with B16F1 or B16F10 cells and granulocyte- or macrophage-rich inflammatory responses were subsequently induced. Analysis of cell yields showed that the percentages of macrophages in the inflammatory exudates of tumour-bearing animals were significantly depressed. No significant changes were noted, however, in the levels of granulocytes in peritoneal exudates from tumour-bearing mice when compared to appropriate controls. In parallel studies, the levels of resident macrophages and granulocytes following lavage of non-stimulated peritoneal cavities of mice with and without tumours were monitored as were the levels of blood monocytes and leukocytes. No consistently significant changes were noted in the levels of blood leukocytes or monocytes in normal or tumour-bearing animals. Furthermore, no consistently significant changes were found in the percentages of granulocytes normally resident in the peritoneal cavities of mice with or without the B16 melanoma. It was found, however, that the percentages of resident macrophages in mice bearing the B16 malignant melanoma were significantly depressed relative to those found in normal animals.

Animals↗
PubMed1985

A study of the adhesive, locomotory and invasive behaviour of Walker 256 carcinosarcoma cells.

We have succeeded in selecting two variant strains of the Walker 256 carcinosarcoma which display markedly different adhesive properties. Both the high (W256A) and the low (W256S) adhesive variants respond chemotactically towards 10(-8) M f-met-leu-phe (FMLP) although there is a significant difference in their locomotory ability. Nevertheless, the fact that the essentially non-adherent W256S cells can migrate in vitro argues against any simple relationship between adhesion and locomotion. We suggest that traction is important in locomotion but that it need not arise only from direct adhesive interaction. We have also tested the invasive behaviour of the W256 variants using an in vitro model system in which disruption of a cellular barrier by the invasive cells can be recorded electrophysiologically. Although leucocytes can penetrate such a barrier they do so only under chemotactic stimulation, whereas W256 tumour cells of either variant strain will do so spontaneously. The tumour variants induce cell retraction within the barrier and this may lead ultimately to cell detachment and death. The holes which arise may then be colonized by tumour cells, and in this way the invasive process could be promoted. The molecular mechanisms by which tumour cells achieve destruction of the cellular barrier are not clear, but it is likely that a number of enzymes are involved.

Animals↗
PubMed1984

Cell adhesion and experimental metastasis: a study using the B16 malignant melanoma model system.

The adhesive properties of B16F1 and B16F10 cells have been studied following their rates of attachment to various substrates and by analysis of their rates of aggregation within the defined environment provided by a cone and plate viscometer. Contrary to previous reports, we found that the B16F10 cells (with significant lung-colonizing potential following tail vein injection) were less homotypically adhesive than B16F1 cells (which colonize lungs poorly). The adhesiveness of B16F10 cells approached that of B16F1 cells only under conditions (low shear, low cell number) where cell collisions were thought to be so few that quantitative differences in aggregation rate could not be determined. B16F1 cells also adhered more to lung cells than did B16F10 cells when assessed by aggregation rate. However, analysis of aggregate composition in which one cell type had been fluorescently labelled showed that B16F10 cells actually formed more mixed aggregates with lung cells than did B16F1 cells. There was no significant difference in the adhesiveness of B16F1 or B16F10 cells to liver cells as assessed by aggregation rate. Analysis of aggregate composition under these circumstances, however, showed that B16F10 cells formed fewer mixed aggregates with liver cells than did B16F1 cells. These results are consistent with the possibility that metastatic cells need to display poor homotypic adhesiveness in order to detach from the primary but enhanced heterotypic adhesiveness in order to colonize specific organs.

Animals↗
PubMed1983

Adaptation of the Boyden chamber to flow conditions: rheological effects on chemotaxis.

Although standard Boyden chambers assess chemotaxis under static fluid conditions they are routinely used as an experimental system to model the dynamic events associated with leukocyte extravasation in vivo. We have adapted the Boyden chamber system by incorporating it within the confines of a cone and plate viscometer which can then be employed to generate known shear conditions as the chemotactically responding cells migrate. Our results show that random locomotion of rat peritoneal exudate cells is stimulated under shear conditions within the range of 11.25-90/s relative to that under static conditions. Furthermore, chemotaxis to the synthetic tripeptide F-Met-Leu-Phe (FMLP) is also stimulated under shear conditions with the peak effect occurring near 22.5/s. This adaptation of the standard chamber system to allow the study of chemotaxis under flow conditions may provide further insight on the migratory properties of leukocytes in vivo.

Animals↗