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Biomedical subjects

A G Messenger

Publications and source records attributed to A G Messenger.

At least 73 records · Page 4Linked to original sources

Distribution of proteoglycans during the hair growth cycle in human skin.

The involvement of proteoglycans in hair growth has been recognized through the observation of increased hair growth in diseases such as the mucopolysaccharidoses and pre-tibial myxedema, which involve an increase in skin proteoglycan content. In an attempt to understand this, we have examined the distribution of chondroitin 6 sulphate (C6S), unsulphated chondroitin (COS), dermatan sulphate (DS), and heparan sulphate proteoglycans (HSPG) in frozen tissue sections of normal scalp by immunostaining. Results show that during anagen, the thick connective tissue sheath around the follicle strains strongly for C6S, COS, and DS. COS is uniquely associated with this region and is not found beneath the epidermis or infundibular epithelium. HSPG is, however, localized in the basement membrane zone adjacent to the outer root sheath. In addition, all of these proteoglycans are localized in the dermal papilla. In mid-catagen, we observed significant loss of C6S and COS staining from both the dermal papilla and the connective tissue sheath, but no decrease in staining for HSPG. In late catagen, very little staining of C6S and COS was observed. In early anagen, we observed that C6S was again present in the connective tissue sheath and dermal papilla; however, COS staining appeared to be weaker and less closely associated with the follicle. HSPG staining was observed in early anagen in a pattern very similar to that found for other basement membrane components. Results for DS were not obtained for catagen or early anagen. These results provide further evidence that hair growth is associated with the presence of chondroitin proteoglycans in the follicle environment and that the cessation of growth is associated with their removal. Further studies are underway to characterize the relationship between hair growth and proteoglycans.

Adult↗

Effect of androgens on the growth of cultured human dermal papilla cells derived from beard and scalp hair follicles.

Androgens stimulate hair growth in some areas, e.g., beard, but may cause regression and baldness on the scalp. The mesenchyme-derived dermal papilla is believed to regulate many aspects of hair growth. It is probable that androgens exert their effect on hair growth via the dermal papilla. In this study the effect of androgens on the growth of cultured dermal papilla cells from beard and non-balding scalp was assessed. Dermal papilla cells from beard hair follicles and non-balding scalp were cultured in vitro in the presence and absence of different concentrations of testosterone or the synthetic, non-metabolizable androgen, mibolerone. Cell growth was reflected by the incorporation of 3H-thymidine. The presence of either androgen did not significantly alter DNA synthesis at any of the concentrations examined in either type of cell line. These results do not mean that dermal papilla cells do not respond to androgens in vitro, but that the measurement of cell growth is an inappropriate method of assessment. Androgens may well stimulate the synthesis of specific proteins that could influence the hair follicle.

Androgens↗

Expression of basement membrane proteins and interstitial collagens in dermal papillae of human hair follicles.

The expression of basement membrane molecules and interstitial collagens in human hair follicle mesenchyme was studied by immunohistochemical staining of tissue sections and of cells cultured from dermal papillae. Type I and type III collagens were found in the dermal sheath and in the dermal papilla throughout the hair cycle. Laminin and type IV collagen were expressed at the outer root sheath basement membrane and in the extracellular matrix of the dermal papilla of anagen and catagen follicles. In telogen follicles, where the volume of the dermal papilla extracellular matrix is much reduced, outline staining of dermal papilla cells for laminin and type IV collagen was still apparent. Staining for bullous pemphigoid antigen was also seen at the outer root sheath basement membrane extending to the lower tip of the hair bulb. In anagen follicles, there was no staining for bullous pemphigoid antigen at the interface between hair bulb epithelium and the dermal papilla and no staining within the dermal papilla. However, linear staining for bullous pemphigoid antigen became continuous around hair follicle epithelium during catagen and telogen. Cells cultured from human dermal papillae also stained for interstitial collagens, type IV collagen and laminin. However, similar results were obtained when cultured dermal fibroblasts were stained with the same antibodies. The expression of basement membrane proteins in human dermal papillae resembles that seen in follicles from other mammalian species and suggests that this is relevant to dermal papilla function. Cultured dermal papilla cells express a similar pattern of interstitial collagens and basement membrane proteins to those seen in tissue sections but this finding is not specific to dermal papilla cells.

Antibodies, Monoclonal↗

Expression of extracellular matrix in hair follicle mesenchyme in alopecia areata.

Human hair follicle mesenchyme contains a distinctive extracellular matrix which varies in volume and composition in concert with the hair growth cycle. To investigate the possibility that mesenchymal function is disturbed in alopecia areata we have studied the expression of extracellular matrix constituents in scalp biopsies from 14 patients by immunohistochemical staining for basement membrane proteins, proteoglycans and interstitial collagens. The staining patterns in follicles from non-lesional scalp were normal. Miniature anagen follicles from bald patches also showed relatively normal expression of basement membrane proteins and proteoglycans. However, in some large anagen follicles from lesional sites, there was loss of the normal staining pattern for chondroitin-6-sulphate in the dermal papilla. In lesional catagen follicles, the glassy membranes showed marked convolution and thickening. These structures stained strongly for laminin and type IV collagen but only weakly for interstitial collagens.

Adolescent↗

Dysplastic naevi in association with partial deletion of chromosome 11.

A patient is reported who developed dysplastic naevi at an early age. He also suffered from a syndrome including Wilms' tumour, aniridia, mental retardation and diabetes mellitus in association with an interstitial deletion of the short arm of chromosome 11. It is suggested that genetic factors may be important in sporadic as well as familial cases of the dysplastic naevus syndrome.

Adult↗

Scarring alopecia in psoriasis.

Scalp biopsies were taken from 3 patients with a scarring alopecia associated with severe scalp psoriasis. The histological findings in each case showed inflammatory destruction of the infundibular region of the hair follicle. The similarity of these changes in each case strongly suggests an association with the psoriasis.

Adult↗

Sunbed-induced pseudoporphyria.

The clinical details of four fair-skinned women with recurrent blistering and skin fragility are presented. All had considerable sun-exposure and had used sunbeds for years. Specific causes of bullous dermatoses including drug ingestion, porphyria, cutaneous amyloidosis and epidermolysis bullosa acquisita were excluded. Long-term recurrent exposure to high doses of sunbed radiation in chronically sun-damaged skin appears to be a further cause of pseudoporphyria.

Adult↗

Granuloma formation in herpes zoster scars.

An 82-year-old male with chronic lymphocytic leukaemia developed an erythematous papular eruption over the trunk. Lesions occurred at the site of scars related to a disseminated herpes zoster infection 3 months previously. Biopsy of a lesion showed granuloma formation. The rash resolved spontaneously over 6-8 weeks.

Aged↗

Calcium/calmodulin regulation of the proliferation of human epidermal keratinocytes, dermal fibroblasts and mouse B16 melanoma cells in culture.

We have investigated the relationship between extracellular calcium, intracellular calmodulin and proliferation in normal keratinocytes. Keratinocyte proliferation and its sensitivity to calmodulin antagonists was compared with that of normal human dermal fibroblasts and neoplastic mouse B16 melanoma cells. Keratinocytes were similar to fibroblasts in showing reduced proliferation in low (0.15 mM) calcium medium and unlike B16 cells which continued to proliferate until calcium was reduced to submicromolar levels. Intracellular calmodulin was significantly higher in rapidly dividing keratinocytes in normal (1.15 mM) calcium medium than in slower dividing cells in low (0.15 mM) calcium. Fibroblasts and B16 cells maintained similar calmodulin levels in both low and normal calcium media. Calmodulin antagonists inhibited proliferation of all three cell types equally. Thus, keratinocyte calmodulin seems related to the proliferative state of the cell (unlike fibroblast calmodulin) and calmodulin antagonists may be of use in controlling the hyperproliferation of the psoriatic epidermis.

Animals↗

Atypical bullous pyoderma gangrenosum associated with myeloid malignancies.

Atypical bullous pyoderma gangrenosum was diagnosed during the course of a myeloid malignancy in three patients. One patient had chronic myeloid leukaemia, one acute myeloid leukaemia, and the third, refractory anaemia with excess of blasts. This atypical form of pyoderma gangrenosum has been specifically associated with myeloid malignancies. The atypical appearance of the skin lesions and the clinical context in which they arose caused the true diagnosis to be delayed in all cases. Treatment with steroids was associated with rapid healing of the skin lesion. The histopathological changes in the skin biopsy specimens from these cases were non-specific, and although the histology was considered to be atypical of pyoderma gangrenosum in one case, the unusual features could be attributed to the patient's neutropenia. (Skin biopsy was performed to exclude other specific pathology). Atypical bullous pyoderma gangrenosum is an uncommon association of the myeloid malignancies. It may remain unrecognised and should be considered more often.

Adult↗

Alopecia areata: alterations in the hair growth cycle and correlation with the follicular pathology.

A histopathological study was performed in 17 patients with alopecia areata to elucidate the changes in hair cycle dynamics. The findings confirm the view that the initial event in alopecia areata is the premature entry of anagen follicles into telogen, although some follicles survive for a time in a dystrophic anagen state. However, after re-entry into anagen takes place, growth appears to be halted in anagen III rather than anagen IV, as has previously been suggested. Follicles then return prematurely to telogen and these truncated cycles are repeated until the disease activity subsides. A new pathogenic hypothesis is presented which relates alterations in hair cycle dynamics to pathological changes within the anagen follicle and also provides an explanation for the formation of exclamation mark hairs and the non-destructive nature of the disease.

Adolescent↗

The in vitro properties of dermal papilla cell lines established from human hair follicles.

The in vitro properties of cells cultured from the dermal papilla of human hair follicles were studied and compared with those of lines of dermal fibroblasts derived from the same material. In serial subcultures, the dermal papilla cells displayed a spread out, polygonal cellular morphology at stationary growth phases and a tendency to form multi-layered aggregates before reaching confluence. Aggregation was particularly marked when papilla cells were grown on collagen gels. In contrast, dermal fibroblasts grew as branching, parallel arrays of spindle-shaped cells which remained as monolayers until confluence. Compared with dermal fibroblasts, papilla cells also exhibited a shorter in vitro survival time. The properties of cultured human papilla cells are similar to those of rat vibrissa papilla cells.

Cell Aggregation↗

Expression of HLA-DR by anagen hair follicles in alopecia areata.

The expression of HLA-DR within hair follicles in alopecia areata was studied using an immunoperoxidase method. Scalp biopsies were taken from 12 patients with alopecia areata and from 6 normal control subjects. Frozen sections were stained with a panel of 4 anti-HLA-DR monoclonal antibodies, Leu 2, Leu 3, Leu 4, and T6 antibodies. The expression of DR in normal hair follicles and in most anagen follicles from nonlesional alopecia skin was confined to dendritic cells which were sparse below the level of the arrector pilorum insertion. Of the 37 anagen follicles examined in lesional skin, 25 displayed staining for DR on epithelial cells in the precortical matrix and presumptive cortex. Six follicles showed DR staining in other epithelial compartments, the lower bulb matrix, inner root sheath, and outer root sheath. Infiltration of the hair bulb matrix by T cells was seen in the majority of follicles where epithelial cells were DR+. The aberrant expression of DR antigens by hair follicle epithelium provides direct evidence that immune mechanisms are operating in the pathogenesis of alopecia areata. In a previous study of alopecia areata we found evidence of cell injury confined to the precortical matrix and presumptive cortex in lesional anagen follicles. The relative restriction of epithelial DR expression to the same site suggests that this region of the follicle is of fundamental importance in the disease process.

Alopecia Areata↗