Leslie Jones

Destruction of the arrector pili muscle and fat infiltration in androgenic alopecia.

Androgenic alopecia (AGA) is the most common hair loss condition in men and women. Hair loss is caused by follicle miniaturization, which is largely irreversible beyond a certain degree of follicular regression. In contrast, hair loss in telogen effluvium (TE) is readily reversible. The arrector pili muscle (APM) connects the follicle to the surrounding skin.

The proteomic profile of hair damage.

Background  Monilethrix is a congenital hair shaft disorder with associated fragility. Many of the changes seen in monilethrix hair on light microscopy and scanning electron microscopy are also seen in hair weathering and cosmetic damage to hair.

Beyond goosebumps: Does the arrector pili muscle have a role in hair loss?

The arrector pili muscle (APM) consists of a small band of smooth muscle that connects the hair follicle to the connective tissue of the basement membrane. The APM mediates thermoregulation by contracting to increase air-trapping, but was thought to be vestigial in humans. The APM attaches proximally to the hair follicle at the bulge, a known stem cell niche. Recent studies have been directed toward this muscles possible role in maintaining the follicular integrity and stability. This review summarizes APM anatomy and physiology and then discusses the relationship between the follicular unit and the APM. The potential role of the APM in hair loss disorders is also described, and a model explaining APM changes in hair loss is proposed.

Primary cicatricial alopecia: diagnosis and treatment

See also practice article by Aslam and Harries on page [1591][1] and at [www.cmaj.ca/lookup/doi/10.1503/cmaj.130305][2] Hair loss is common, the most prevalent disorders being androgenetic alopecia (male pattern baldness) and alopecia areata. Alopecia areata and androgenetic alopecia are

Androgenetic alopecia: new insights into the pathogenesis and mechanism of hair loss

The hair follicle is a complete mini-organ that lends itself as a model for investigation of a variety of complex biological phenomena, including stem cell biology, organ regeneration and cloning. The arrector pili muscle inserts into the hair follicle at the level of the bulge- the epithelial stem cell niche. The arrector pili muscle has been previously thought to be merely a bystander and not to have an active role in hair disease. Computer generated 3D reconstructions of the arrector pili muscle have helped explain why women with androgenetic alopecia (AGA) experience diffuse hair loss rather than the patterned baldness seen in men. Loss of attachment between the bulge stem cell population and the arrector pili muscle also explains why miniaturization is irreversible in AGA but not alopecia areata. A new model for the progression of AGA is presented.

Characterization and causal investigations of an alopecia syndrome in Australian fur seals (Arctocephalus pusillus doriferus)

Abstract Fur seals rely on pelage consisting of dense, fine underfur protected by guard hairs as their primary means of limiting thermoregulatory cost. A distinctive syndrome of alopecia occurs at high prevalence in 1 colony of Australian fur seals (Arctocephalus pusillus doriferus). It is characterized by bilaterally symmetrical hair loss on the dorsal body surface and a biased prevalence toward juvenile females. Light and scanning electron microscopy demonstrated that alopecia is due to fracture of the hair shaft above the skin level. No evidence of viral, bacterial, fungal, or parasite infection was found and histological examination of skin biopsies revealed no pathological variation between case and control seals. Affected animals had statistically significant lower tyrosine and zinc concentrations in hair than unaffected seals. This may increase hair brittleness and, therefore, predispose its fracture. Alopecia cases also had higher levels of heavy metals and persistent organic pollutants, which may indicate they forage in ecosystems where concentrations of pollutants are higher.

Location of keratin-associated proteins in developing fiber cuticle cells using immunoelectron microscopy

Aims: To investigate the location of keratin-associated proteins (KAPs) in developing hair fiber cuticle cells using transmission electron microscopy with immunogold techniques and specific antibodies. Other studies were aimed at detecting the presence of cornified envelope proteins including involucrin and loricrin. Mateials and Methods: Polyclonal antibodies were produced in rabbits against peptides from KAPS 5.1, KAPS 10.1 ultra high-sulfur proteins. Results: The KAP proteins were found to form part of the developing exocuticle and a- layer. Cornified envelope proteins (involucrin and loricrin) were absent consistent with recent findings. Conclusions: The results have been discussed in terms of a revised model for fiber cuticle surface barriers including their role in fiber cuticle surface function.

The arrector pili muscle, the bridge between the follicular stem cell niche and the interfollicular epidermis

Proximally, the arrector pili muscle (APM) attaches to the follicular stem cell niche in the bulge, but its distal properties are comparatively unclear. In this work, a novel method employing an F-actin probe, phalloidin, was employed to visualize the APM anatomy. Phalloidin staining of the APM was validated by comparison with conventional antibodies/stains and by generating three-dimensional reconstructions. The proximal attachment of the APM to the bulge in 8 patients with androgenic alopecia was studied using Masson’s trichrome stain. Phalloidin visualized extensive branching of the APM. The distal end of the human APM exhibits a unique “C”-shaped structure connecting to the dermal–epidermal junction. The proximal APM attachment was observed to be lost or extremely miniaturized in androgenic alopecia. The unique shape, location, and attachment sites of the APM suggest a significant role for this muscle in maintaining follicular integrity. Proximally, the APM encircles the follicular unit and only attaches to the primary hair follicle in the bulge; this attachment is lost in irreversible hair loss. The APM exhibits an arborized morphology as it ascends toward the epidermis, and anchors to the basement membrane.

Chemiluminescence from UVA-exposed skin: separating photo-induced chemiluminescence from photophysical light emission.

Several previous studies have reported luminescence emission from skin following exposure to UVA radiation in air. We show that UVA irradiation of biomaterials and polymers in oxygen, including bovine stratum corneum, followed by photon counting results in a complex emission due to a combination of photophysical processes together with photo-induced chemiluminescence (PICL). The photophysical processes include fluorescence, phosphorescence and charge-recombination luminescence. By irradiating materials in an inert atmosphere such as nitrogen and allowing photophysical light emission to fully decay before admitting oxygen, the weak photo-induced chemiluminescence generated via free radical reactions with oxygen can be separated and analysed. PICL emission from bovine stratum corneum is weaker than for wool keratin and bovine skin collagen, probably due to its higher water content, and the presence of the natural antioxidants ascorbate and tocopherol.

Bioprospecting keratinous materials.

The concept of bioprospecting for bioactive peptides from keratin-containing materials such as wool, hair, skin and feathers presents an exciting opportunity for discovery of novel functional food ingredients and nutraceuticals, while value-adding to cheap and plentiful natural sources. The published literature reports multiple examples of proline-rich peptides with productive bio-activity in models of human disease including tumour formation, hypertension control and Alzheimer’s disease. Bioactive peptides have been identified from food and other protein sources however the bioactivity of keratin-related proteins and peptides is largely unknown. Considering the high representation of proline-rich peptides among proven bioactive peptides, the proline-rich character of keratinous proteins supports current research. A selection of mammalian (cow epidermis, sheep wool) and avian (chicken feather) keratinous materials were subjected to enzymatic hydrolysis using established processing methods. A bio-assay of determining inhibition of early stage amyloid aggregation involved using a model fibril-forming protein – reduced and carboxymethylated bovine K-casein (RCMk-CN) and quantitation of fibril development with the amyloid-specific fluorophore, Thioflavin T (ThT). The assay was fully validated for analytical repeatability and used together with appropriate positive controls. Peptide library products derived from chicken feather (n=9), sheep wool (n=9) and bovine epidermis (n=9) were screened in the fibril inhibition assay based on K-casein. 3 of 27 products exhibited interesting levels of bio-activity with regard to fibril inhibition. HPLC profiles provide an indication of the complexity of the assemblage of peptides in the three active products. We conclude the bioprospecting research using keratinous materials shows promise for discovery of useful bioactive peptides.