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Manchester, United Kingdom

Miranda B.H.,University of Bradford | Farjo N.,Farjo Medical Center | Farjo B.,Farjo Medical Center
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2011

A novel and successful case of eyebrow reconstruction, in dormant keratosis pilaris atrophicans, is presented. Keratosis pilaris atrophicans is a benign hereditary disorder of unknown aetiology. Grouped keratotic follicular papules and perifollicular erythema affect the cheeks and eyebrows, with a subsequent atrophic stage that results in scarring and alopecia. It often presents during early infancy with remission during adulthood. A 33 year old man presented with scarring and alopecia of the eyebrows and was followed over a total 4 year period during which reconstruction was achieved using individual hair follicle micrografts. Composite scalp grafts and flaps, more often than hair follicle micrografting techniques, are described in the literature for reconstruction of the eyebrows in a range of conditions. This case provides an encouraging example of successful micrografting in dormant inflammatory cutaneous disease. © 2011 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

Hardman J.A.,University of Manchester | Tobin D.J.,University of Bradford | Haslam I.S.,University of Manchester | Farjo N.,Farjo Medical Center | And 5 more authors.
Journal of Investigative Dermatology | Year: 2015

Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies. © 2015 The Society for Investigative Dermatology.

Al-Nuaimi Y.,University of Manchester | Hardman J.A.,University of Manchester | Biro T.,Debrecen University | Haslam I.S.,University of Manchester | And 10 more authors.
Journal of Investigative Dermatology | Year: 2014

The hair follicle (HF) is a continuously remodeled mini organ that cycles between growth (anagen), regression (catagen), and relative quiescence (telogen). As the anagen-to-catagen transformation of microdissected human scalp HFs can be observed in organ culture, it permits the study of the unknown controls of autonomous, rhythmic tissue remodeling of the HF, which intersects developmental, chronobiological, and growth-regulatory mechanisms. The hypothesis that the peripheral clock system is involved in hair cycle control, i.e., the anagen-to-catagen transformation, was tested. Here we show that in the absence of central clock influences, isolated, organ-cultured human HFs show circadian changes in the gene and protein expression of core clock genes (CLOCK, BMAL1, and Period1) and clock-controlled genes (c-Myc, NR1D1, and CDKN1A), with Period1 expression being hair cycle dependent. Knockdown of either BMAL1 or Period1 in human anagen HFs significantly prolonged anagen. This provides evidence that peripheral core clock genes modulate human HF cycling and are an integral component of the human hair cycle clock. Specifically, our study identifies BMAL1 and Period1 as potential therapeutic targets for modulating human hair growth. © 2014 The Society for Investigative Dermatology.

Khidhir K.G.,University of Bradford | Woodward D.F.,Allergan, Inc. | Farjo N.P.,Farjo Medical Center | Farjo B.K.,Farjo Medical Center | And 4 more authors.
FASEB Journal | Year: 2013

Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized that another serendipitous discovery, increased eyelash growth side-effects of prostamide F2-related eyedrops for glaucoma, may be relevant for scalp alopecias. Eyelash hairs and follicles are highly specialized and remain unaffected by androgens that inhibit scalp follicles and stimulate many others. Therefore, we investigated whether non-eyelash follicles could respond to bimatoprost, a prostamide F2 analog recently licensed for eyelash hypotrichosis. Bimatoprost, at pharmacologically selective concentrations, increased hair synthesis in scalp follicle organ culture and advanced mouse pelage hair regrowth in vivo compared to vehicle alone. A prostamide receptor antagonist blocked isolated follicle growth, confirming a direct, receptormediated mechanism within follicles; RT-PCR analysis identified 3 relevant receptor genes in scalp follicles in vivo. Receptors were located in the key follicle regulator, the dermal papilla, by analyzing individual follicular structures and immunohistochemistry. Thus, bimatoprost stimulates human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and scalp follicles contain bimatoprost-sensitive prostamide receptors in vivo. This highlights a new follicular signaling system and confirms that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias. © FASEB.

Upton J.H.,Center for Cutaneous Research | Hannen R.F.,Center for Cutaneous Research | Bahta A.W.,Center for Cutaneous Research | Farjo N.,Farjo Medical Center | And 2 more authors.
Journal of Investigative Dermatology | Year: 2015

Dermal papilla cells (DPCs) taken from male androgenetic alopecia (AGA) patients undergo premature senescence in vitro in association with the expression of p16 INK4a, suggesting that DPCs from balding scalp are more sensitive to environmental stress than nonbalding cells. As one of the major triggers of senescence in vitro stems from the cell "culture shock" owing to oxidative stress, we have further investigated the effects of oxidative stress on balding and occipital scalp DPCs. Patient-matched DPCs from balding and occipital scalp were cultured at atmospheric (21%) or physiologically normal (2%) O 2. At 21% O 2, DPCs showed flattened morphology and a significant reduction in mobility, population doubling, increased levels of reactive oxygen species and senescence-associated β-Gal activity, and increased expression of p16 INK4a and pRB. Balding DPCs secreted higher levels of the negative hair growth regulators transforming growth factor beta 1 and 2 in response to H 2 O 2 but not cell culture-associated oxidative stress. Balding DPCs had higher levels of catalase and total glutathione but appear to be less able to handle oxidative stress compared with occipital DPCs. These in vitro findings suggest that there may be a role for oxidative stress in the pathogenesis of AGA both in relation to cell senescence and migration but also secretion of known hair follicle inhibitory factors. © 2015 The Society for Investigative Dermatology.

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