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Biomedical subjects

A L Muggleton-Harris

Publications and source records attributed to A L Muggleton-Harris.

At least 37 records · Page 2Linked to original sources
PubMed1987

Factors modulating mouse lens epithelial cell morphology with differentiation and development of a lentoid structure in vitro.

The morphological and cellular changes that occur with differentiation and development of a lentoid structure from cultured mouse lens epithelial cells have been found to be dependent on the presence of lens capsule in association with the cells. The development of the 'lentoid body' is a multiphase process involving cell replication, synthesis of mucosubstances and a basement collagen membrane, cell aggregation and differentiation. Stage-specific synthesis of lens proteins confirms that the genes regulating normal differentiation in vivo are operating in the in vitro system. The hydrated collagen gel studies described in this report demonstrate that the cuboidal morphology and apical-basal polarity of the lens epithelial cells are dependent on their relationship with the lens capsule. Following a replicative phase the cells assume a mesenchyme-like morphology and migrate into the gel. Trypsinized cells freed from the lens capsule replicate but form colonies on the surface of the gel. The implications of these results are discussed with respect to previous observations made on normal lens development and the abnormalities associated with the congenital cataractous embryonic lens.

Animals↗
PubMed1987

Rescue of developmental lens abnormalities in chimaeras of noncataractous and congenital cataractous mice.

In the study of the lens of a congenital cataractous mouse mutant (CAT), it has been shown that a loss of growth regulation at the cellular level causes gross lens abnormalities. The phenotypic characteristics of the cataractous mouse lens are similar to those seen in human congenital cataract and thus serves as a model system for medical research. In this present investigation, we have demonstrated that the abnormalities of the congenital cataractous lens can be rescued by forming chimaeras between DBA/2 (a noncataractous strain of mouse) and the CAT mutant. This report describes the histological, cellular and biochemical analysis of the resultant chimaeric eyes, and discusses possible mechanisms by which these results were achieved.

Animals↗
PubMed1985

Age-dependent metabolic changes in cultured human fibroblasts.

The effects of metabolic poisons on the ATP content of cultured human skin fibroblasts at selected in vitro and in vivo ages were studied. Potassium cyanide, iodacetamide, and Arsenate were used to inhibit ATP restoration by glycolysis and oxidative phosphorylation. Cells treated with these metabolic poisons showed an age-dependent change in their ATP content. The decrease in cellular ATP content after exposure to these drugs was taken as an estimate of ATP turnover. It was found that there was a decrease in the ATP turnover with increasing population doubling level (i.e. in vitro age), and cells cultured from a 68-yr-old donor had a lower ATP turnover than those cultured from a neonatal donor. This decreased ATP turnover correlates with a previous finding of a decreased ability of "older" cells to be stimulated to migrate in culture and suggests that there is a metabolic component to this age-related functional deficiency.

Adenosine Triphosphate↗
PubMed1982

Replicative potential of individual cell hybrids derived from young and old donor human skin fibroblasts.

Neonatal, adult, and aged donor human skin fibroblast cell cultures have been characterized for the population doubling potential and in vitro-in vivo relationship. Hybrid cells derived from individual whole-cell fusions of replicating GRC 387 (aged) and CSC 303 (neonatal) cells demonstrated that an intermediate mode of replication between that of the two parental cell lines occurred; therefore the longevity of the aged fibroblast cells was enhanced. The GRC 387 cells have an extended post-replicative phase-out period in comparison with the CSC 303 cells, and the experimental hybrids demonstrated a 20-25% increase of the period over that of the GRC 387 cells.

Aging↗
PubMed1982

Modification of the cataractous phenotype by somatic cell hybridization.

Characterized mouse lens epithelial cell cultures and their clonal isolates obtained from normal and cataractous mice display a finite life-span. The cells of cataractous origin have a decreased number of population doubling levels compared to the capacity of the normal cells to replicate in vitro. Hybrid cells derived from individual cell fusions of normal (CD-1, DBA/2) and cataractous (Catfr) lens epithelial cells have a mode of replication similar to that of normal cells. These results demonstrate that the abnormal in vitro replicative state of the cataractous cells has been modified by the addition of normal lens epithelial cell components.

Animals↗
PubMed1982

In vitro characterization of response to stimulus (wounding) with regard to ageing in human skin fibroblasts.

Confluent cultured normal human skin fibroblasts from neonatal, adult and aged donors have been stimulated to respond to wounding of the cell sheet. The latent period prior to initial migration of cells from the leading edge of the monolayer is correlated with in vitro population doubling level and in vivo donor age. Time-lapse photography of areas along the edge of the cell sheet reveals a specific pattern of migration by which the cells reestablish a confluent monolayer.

Aging↗
PubMed1980

Replicative potentials of various fusion products between WI-38 and SV40 transformed WI-38 cells and their components.

Hybrid cells derived from whole-cell fusions of replicating phase-II normal fibroblast cells (WI-38s) with SV40 transformed WI-38 fibroblast cells (CL-1s) demonstrated that the majority of the hybrid experimental cells still maintained a finite life-span. Approximately 2% demonstrated sustained and possibly indefinite replication. Experimental binucleate cells and subsequent hybrid synkaryons were also formed by fusing CL-1 karyoplasts into phase-II WI-38 replicating normal fibroblasts. In addition, viable cells were constructed from WI-38 fibroblast cytoplasts with CL-1 karyoplasts. Sustained replication was not observed in these crosses.

Cell Division↗
PubMed1976

The nature and distribution of serologically detectable alloantigens on the preimplantation mouse embryo.

The nature and distribution of surface alloantigens on preimplantation mouse embryos has been examined by immunofluorescence. Non-H-2 alloantigens were detected at all stages examined, from the 2-cell to the 4 1/2-day blastocyst. Cleaving blastomeres, inner cell mass cells and cells of the primary trophectoderm were all positive. In F1 embryos maternal non-H-2 alloantigens were detectable at all stages, whereas paternal antigens first became evident at the 6- to 8-cell stage. No convincing evidence of the presence of alloantigens associated with the H-2 haplotype was found at any stage or on any cell type, suggesting that if these antigens are present they are in low quantity or are masked.

Animals↗
PubMedDate not supplied

Criteria that optimize the potential of murine embryonic stem cells for in vitro and in vivo developmental studies.

Cultured mouse embryonic stem (ES) cells are used for both in vitro and in vivo studies. The uncommitted pluripotent cells provide a model system with which to study cellular differentiation and development; they can also be used as vectors to carry specific mutations into the mouse genome by homologous recombination. To ensure successful integration into the germ line, competent totipotent diploid ES cell lines are selected using a cell injection bioassay that is both time consuming and technically demanding. The prolonged in vitro culture of rapidly dividing ES cells can lead to accumulated changes and chromosomal abnormalities that will compromise the biological function and abrogate germ line transmission of chimeric mice carrying novel genetic mutations. Such in vitro conditions will vary between individual laboratories; for example, differences in the serums used for maintenance. Using a number of different criteria we attempt in this paper to define the parameters that we found to be key factors for optimization of the biological potential of established ES cell lines. The successful integration into the germ line is dependant on acquiring or deriving a competent totipotent mouse ES diploid cell line. In this paper parameters and criteria are defined which we found to be key factors for the optimization of the biological potential of established ES cell lines.

Animals↗