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Biomedical subjects

R F Oliver

Publications and source records attributed to R F Oliver.

At least 19 recordsLinked to original sources

The DEBR rat: an animal model of human alopecia areata.

The Dundee experimental bald rat (DEBR) is reported as a model for human alopecia areata. Parallels with human alopecia areata were observed in relation to the gradual and patchy loss of hair and the penetration of both pelage and vibrissa follicles by mononuclear cells. In particular, the apparent disruption of the follicles within the precortical region of the epidermal component and consequent alterations of normal geometrical relationships between dermal and epidermal components relate directly to similar studies on human alopecia areata. In comparison with other previously described hypotrichotic rodent mutants, the DEBR rat exhibits a unique mechanism of hair loss which may provide important information regarding the pathomechanism of human alopecia areata.

Alopecia Areata

Dermal cell populations show variable competence in epidermal cell support: stimulatory effects of hair papilla cells.

A study was made of the comparative abilities of adult rat vibrissa dermal papilla cells, skin fibroblasts and 3T3 cells to support the initial attachment and subsequent growth and division of directly associated newborn rat skin basal epidermal cells. These associations were made under sub-optimal conditions; that is, in the absence of specific epidermal growth-promoting supplements, in order to assess more accurately the epidermal sustaining capacities of each dermal support. Analysis of epidermal cell counts and close photographic scrutiny revealed that low-passage dermal papilla cells, closely followed by transformed dermal papilla cells, were conducive to the successful attachment and subsequent proliferation of epidermal cell populations under three different experimental protocols. In contrast, skin fibroblasts did not support epidermal cell growth under any circumstances. These findings are particularly interesting in that they constitute a rare in vitro example of epidermal cells that are not only supported, but also encouraged to proliferate, by an actively dividing adult skin-derived dermal cell population.

Animals

Immunobiological studies on the alopecic (DEBR) rat.

The Dundee experimental bald rat (DEBR) has been proposed as an animal model of human alopecia areata, which is suspected of being an autoimmune disease. This study was carried out to establish whether the immunological changes observed in the lesional DEBR rat correlated with studies of human alopecia areata. The immune infiltrate was characterized using immunoperoxidase techniques on cryostat sections of vibrissa follicles. Indirect immunofluorescence was used to quantify the peripheral blood leucocytes. Some parallels were observed in the infiltration of human and DEBR rat follicles by T lymphocytes. In contrast, pre-lesional DEBR rat follicles, which are not available for investigation in human alopecia areata, were not penetrated by leucocytes and MHC class II antigens were expressed in the precortical region of the epidermal component of these follicles. Quantification of peripheral blood leucocytes showed significant increases in both T-lymphocyte subsets during lesional expression. We consider that the pre-lesional form of the rat may provide important information as a model for the pre-lesional and uninvestigated form of alopecia areata in man.

Alopecia Areata

Whisker growth induced by implantation of cultured vibrissa dermal papilla cells in the adult rat.

Retention of the capacity to induce the growth of hair by cultured adult rat vibrissa dermal papilla cells has been investigated. Small pellets of serially cultured papilla cells were implanted into the bases of the exposed follicular epidermis of amputated adult rat vibrissa follicles. Amputated follicles that received no cell implants or implants of cultured dorsal skin fibroblasts were used as controls. Over 50% of follicles implanted with cultured papilla cells in the passage range 1-3 grew hairs. In contrast none of the follicles that received late passage cells (range 6-15) produced hairs; and spontaneous regeneration of hair occurred in only 3% of the control follicles. These results demonstrate that cultured papilla cells of early passage numbers retain their ability to induce hair growth. Histological examination confirmed that the implanted papilla cells interacted with follicular epidermis to organize the development of new, hair-producing bulbs, each containing a discrete dermal papilla. An important observation was that aggregative behaviour leading to papilla formation was only manifested by early passage papilla cell implants. This persisting embryonic characteristic appears to be an essential functional component of papilla cell activity which operates to regulate the profound morphogenetic changes that occur during the hair growth cycle.

Animals

Reconstruction of full-thickness loss skin wounds using skin collagen allografts.

Sheets of allogeneic dermal collagen measuring 20 X 15 mm and prepared by trypsin treatment of full-thickness skin were grafted under skin flaps in rats. After 2 to 5 weeks the protective recipient skin was excised and replaced by split-thickness skin isografts which remained viable on their supportive collagen beds. On average such composite grafts maintained 84 per cent of their original size over 3 to 28 weeks and in contrast with split-thickness skin grafts achieved full-thickness reconstruction of the excised skin.

Animals

An autoradiographic study of 3H-thymidine incorporation and distribution in the dermis of healing skin incisions in the pig.

The dermal response to injury in healing incisional wounds aged from 1 to 24 days was studied by in vitro and in vivo 3H-thymidine (3HT) labelling and the use of colcemid to induce metaphase arrest. In vitro 3HT labelling provided mean numbers (+/- s.e. mean) of labelled dermal cells/section within the incision and in 3 zones in the dermis up to 0.875 mm lateral to the incision. There was a progressive increase in the numbers of DNA-synthesizing cells in the incisions as granulation tissue developed from Day 1 to Day 7, and a sharp decline by Day 9. Immediately adjacent to the incision there was a dramatic increase in the number of labelled cells on Day 2, with reduced numbers laterally. This response, which was largely maintained up to 7 days, paralleled the cellular reaction around blood vessels and skin appendages but also included labelled dermal fibroblasts. The in vivo 3HT study, taken in conjunction with the colcemid and in vitro 3HT studies, supported the idea that during the development of granulation tissue there is a continual recruitment of paraincisional cells, including dermal fibroblasts, either by direct migration or by division and then migration, as well as by continued mitosis of cells already within the incision.

Animals

Incorporation of stored cell-free dermal collagen allografts into skin wounds: a short term study.

Allogeneic dermal collagen has been evaluated as an alternative to skin autografts for the permanent replacement of lost or damaged skin in the rat. All non-collagenous structures were removed from full-thickness back skin by treatment with a solution of crystalline trypsin. Such dermal collagen preparations were grafted into skin wounds, examined up to 8 1/2 weeks after operation, and compared with excised wounds and skin isografts and allografts of the same initial size. The dermal collagen grafts, particularly when dressed with a sheet of dermal collagen, become recellularised, revascularised and re-epidermalised. Unlike the skin allografts, there was no evidence of cellular rejection. Whereas contracture of the excised wounds was delayed, but not suppressed, by applying a conventional dressing, collagen grafts maintained from 60 to 100 per cent of their original size. In contrast, equivalent skin isografts shrank to 50-60 per cent and showed persistent epidermal hyperplasia.

Animals

Morphological changes associated with the growth cycle of vibrissal follicles in the rat.

Morphological changes which occur in the growth cycle of the rat vibrissal follicle during the transitional period between consecutive anagen phases are described. In contrast with pelage hair follicles, there is no shortening of the follicle, no formation of a papilla 'rest' and no close synchrony between club differentiation and follicle regression. Telogen is therefore considered to occur after loss of the matrix of the hair bulb and maximal diminution of the dermal papilla to a small aggregation of cells. These difference are discussed in relation to current nomenclature of the hair cycle and the function of the vibrissal follicle.

Animals