Thesis (MSPD(Prof)) - University of Queensland, 2002. / Includes bibliography.

The dermal papillae of the hair follicle control its growth, differentiation and apoptosis via a range of growth factors. These secreted growth factors are known to differ between those of non-balding scalp and those of balding scalp and can even differ in response to a common stimuli – androgen. In balding scalp androgen stimulates the secretion of negative growth factors, while in non-balding scalp androgen is found to exert little or no effect. Dermal papilla cells (DPCs) can be cultured in vitro, however those from balding scalp have been found to undergo premature senescence compared to those from non-balding scalp. A major cause of premature senescence is oxidative stress – the gradual accumulation of reactive oxygen species within the cell causing deleterious loss of function. Reactive oxygen species are known to be mediated in response to androgens and growth factors and in turn may affect growth factor signalling within the cell. Using low oxygen cell culture as a means of reducing oxidative stress, balding and non-balding DPCs were grown and characterised. It was confirmed that low oxygen culture could increase proliferation, delay senescence and reduce reactive oxygen species with both DPC types and that balding DPCs showed a higher sensitivity to oxidative stress. It was also found that secretions of growth factors by the balding DPCs in response to different oxygen conditions differed greatly to that of the occipital DPCs. Androgen, but not TGF-β was found to modulate DPC production of catalase, an antioxidant, under low oxygen conditions and this caused a reduction in reactive oxygen species in the balding DPCs. Balding DPCs also demonstrated an upregulation of the antioxidant total glutathione, however had a reduced fraction of the active reduced form of the molecule. In addition, it was shown for the first time 3 that under cell culture conditions balding DPCs express TGF-β receptors and it was shown that proliferation and migration of the balding DPCs could be affected by addition of exogenous TGF-β, highlighting a potential role for TGF-β as an autocrine growth factor in the balding dermal papilla.

Thèse (M.A.) -- Université du Québec à Chicoutimi, 2003. / Bibliogr.: f. 44-45. Document électronique également accessible en format PDF. CaQCU

Alopecia areata (AA) is a complex autoimmune disease in which autoreactive T cell-mediated attack of the hair follicle (HF) leads to non-scarring hair loss. Although AA is one of the most prevalent autoimmune diseases, the development of novel effective therapeutics has been limited. Standard of care remains observation for mild cases and steroids for moderate-to-severe cases, which have demonstrated only limited efficacy. The skin is a highly heterogeneous tissue at baseline, comprised of a diverse array of immune and non-immune cell types whose coordinated crosstalk is essential for homeostasis. The skin microenvironment becomes markedly altered as a result of disease-associated inflammation in AA. A pathognomonic histopathologic feature of AA is an intense lymphocytic infiltrate surrounding the lower portion of the HF in the growth phase of the hair cycle, known as anagen. We previously established that CD8+ T cells comprise the majority of this infiltrate in AA skin, and that they are necessary and sufficient to drive disease via JAK/STAT activation. While this discovery led to the pioneering use of JAK inhibitors as a novel class of therapeutics in AA, JAK inhibition is not a curative solution, since patients often experience relapse upon discontinuation of treatment. This not only underscores the continued need for translational drug discovery research in AA, but also reflects an incomplete understanding of the mechanisms that govern disease pathophysiology. Recent advances in single-cell RNA sequencing (scRNAseq) present an unprecedented opportunity to dissect the heterogeneity of complex tissues and disorders. Since its emergence, scRNAseq has proven to be a powerful tool for the discovery of rare cell types and novel therapeutic targets in a variety of contexts that range from cancer to autoimmunity. In this thesis, we leveraged scRNAseq to interrogate the cellular and molecular mechanisms underlying disease pathogenesis in AA at single-cell resolution, together with validation and functional experiments, with the goal of uncovering novel cell types and pathways that can guide the development of innovative therapeutic strategies. In Chapter 2, we performed scRNAseq of skin-infiltrating CD45+ immune cells to dissect lymphocyte heterogeneity in both murine and human AA. Our scRNAseq analyses informed a series of antibody-mediated cell depletion experiments that assessed the in vivo function of specific lymphocyte subsets in murine AA. Our results established CD8+ T cells as the predominant disease-driving cell type in AA. We identified shared mechanisms underlying CD8+ T cell heterogeneity in murine and human AA skin, in which CD8+ T cells form an “effectorness gradient” comprised of interrelated transcriptional states that culminate in increased expression of inflammatory cytokines and T cell effector function. We also demonstrated a role for CD4+ T helper cells in disease initiation, and determined that regulatory T cells possess intact immunosuppressive capacity in AA. In Chapter 3, we expanded upon the studies described in Chapter 2 and performed scRNAseq of skin-infiltrating CD45+ cells at various timepoints throughout disease course (from 3 to 24 weeks post-disease induction) in AA to analyze the temporal dynamics of lymphocyte heterogeneity in AA skin and skin-draining lymph nodes. In conjunction with scRNAseq, we also performed single-cell TCR sequencing to assess the dynamics of T cell clonality alongside changes in T cell transcriptional profiles. We observed a striking increase in CD8+ T cell clonal expansion during disease onset, which increased throughout disease progression and subsequently decreased in chronic AA, when the preclinical mouse model exhibits total body hair loss. Our single-cell analyses suggested that CD8+ T cell clonality and pathogenicity are closely linked, which we validated in vivo by demonstrating that a single expanded clonotypic population of CD8+ T cells is sufficient to induce disease in mice. In Chapter 4, we analyzed single-cell transcriptomic profiles obtained from full-thickness skin in mice with chronic AA to investigate the contributions of the HF and other non-T cell populations in disease. In this study, we also used a network biology-based approach to infer single-cell protein activity, which together with single-cell mRNA gene expression profiles uncovered a multitude of novel findings in AA. Our results revealed a role for necroptosis as a potential HF-intrinsic mechanism of pro-inflammatory signaling in AA, and also identified an MHC Class II signature specific to basal keratinocytes in AA skin. Furthermore, we uncovered a novel, rare population of disease-associated Arg1+ macrophages, which prompted us to revisit our immune-specific scRNAseq datasets described in Chapters 2 and 3 and perform an integrative analysis of this novel cell type in AA. Our preliminary in vivo studies suggested that targeting Arg1+ macrophages and/or arginine metabolism may ameliorate disease in AA. Taken together, this thesis presents a comprehensive, systematic interrogation of AA pathogenesis at single-cell resolution. Importantly, the validation and functional studies that were informed by our scRNAseq data demonstrate proof-of-concept of the use of single-cell technology to accelerate the discovery and translation of novel therapeutic targets in complex diseases. While we undertook a hypothesis-driven approach to design our studies, the data presented in this thesis was also profoundly hypothesis-generating, and has informed a number of ongoing projects in the laboratory with the shared goal of advancing our understanding of disease pathology in AA.

Hair plays an important role in human social and sexual communication. The androgen-stimulated, patterned loss of hair in cases of androgenetic alopecia (or common baldness) in genetically pre-disposed individuals, is associated with ageing and can cause marked phychological distress. However, it is poorly controlled. To investigate the effectiveness of daily topical application of a Chinese medicine-derived herbal mixture, Xiantene, on balding progression, two double-blind, placebo-controlled studies (3 and 12 months) were carried out on balding men using the trichogram approach. Xiantene significantly increased both the total number of hairs and those in anagen, improving the ratio of anagen:telogen hairs. This suggests that topical Xiantene increased the length of the anagen phase and may promote a cessation, or partial reversal, of the progression of androgenetic alopecia in men. Canities, loss of scalp hair colour, is another mark of ageing. To investigate whether early greying may protect follicles from androgenetic alopecia, the extent of alopecia, assessed using the Hamilton scale, was compared between men who first became grey before, or after, 30. Both alopecia and greying increased with age in 843 men (217 European, 626 Thai) whenever they first started greying. However, men who showed greying before 30 were significantly less bald, though more grey, in both groups. Hair follicle melanocytes synthesise the pigment melanin, producing reactive oxygen species (ROS) and oxidative stress; losing melanocyte pigmentary activity, and therefore these toxic factors, appears to enable hair follicles to maintain their full size for longer, despite the androgen drive to miniaturisation.

The main aim of this dissertation is to discuss the way women negotiate the cultural meaning of hair loss, alopecia, as a result of undergoing chemotherapy, and to understand, accordingly, how cancer's cultural effects regarding women can be deeply different from those of men. Very few studies have been done about the cultural impact and resonance of alopecia. It is often regarded as "secondary" to other effects of chemotherapy. Because, in many cultures, head hair for women expresses or manifests attractiveness and power, to be bald is to be deprived of the ability to fit into society, whether in the public or private sphere. The study examines the representation of such women in the media, audience/subject responses to these representations, and interrogates women's identities and representations in terms of Laura Mulvey's theory of the male gaze. Women who have experienced chemotherapy-induced alopec ia were interviewed in this regard. Other contributive feminist, cultural and/or media studies works, such as those by Suzanna Walters, Susan Bordo, Naomi Wolf, Donna Haraway, Stuart Hall, Kimberle Crenshaw, and Judith Butler, help facilitate the analysis. From these perspectives, a historical analysis takes into consideration the symbolic dimension of hair, especially women's head hair, within Western cultural history, particularly in France and a multicultural America. In addition, a textual analysis looks at women, cancer, and hair loss as represented in popular culture characters and personalities. The study insists on the necessity for women to resist to the culture industries and deconstruct the male gaze, as well as the female gaze, which can both contribute to, and perpetuate women's objectification. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-10-09T12:17:33Z No. of bitstreams: 1 Ademir Carvalho Leite Júnior.pdf: 1086030 bytes, checksum: a4a25c152f48c5f898a986313b25dbe0 (MD5) / Made available in DSpace on 2017-10-09T12:17:33Z (GMT). No. of bitstreams: 1 Ademir Carvalho Leite Júnior.pdf: 1086030 bytes, checksum: a4a25c152f48c5f898a986313b25dbe0 (MD5) Previous issue date: 2017-09-29 / Frontal fibrosing alopecia (AFF) is a primary cicatricial alopecia that was described in 1994. It predominantly affects women, most often in menopause. Studies have shown that alopecias, in general, may have stress as a trigger and maintenance factor. Regarding cicatricial alopecia, especially AFF, the relevance of these factors was little studied, however, studies suggest that stressful events may be associated with the onset of alopecia conditions. The objective of this study is to evaluate the relevance of suffering as a stressful event as a possible triggering factor for AFF patients. To perform this evaluation a socio-demographic form, a quality of life inventory in Dermatology (DQLI) and a semi-structured interview was held in a single meeting with the research volunteers. The 12 volunteers in the study present life stories with intense reports of frustration, impotence, insecurity, loss, shame and loneliness. DQLI, used to assess the impact of AFF on the life of the volunteers, was consistent with the observations made by them, that the disease accompanies a high degree of stress and suffering / A Alopecia Fibrosante Frontal (AFF) é uma alopecia cicatricial primária que foi descrita em 1994. Acomete predominantemente mulheres, na maior parte das vezes na menopausa. Estudos mostram que as alopecias, em geral, podem ter como fator causal e de manutenção o estresse. Sobre as alopecias cicatriciais, em especial a AFF, a relevância destes fatores foi pouco estudada, ainda assim, estudos sugerem que eventos estressantes podem estar associados ao surgimento de alopecias. O objetivo deste estudo é avaliar a relevância do sofrimento tendo o evento estressante como possível fator desencadeante de quadros de AFF. Para realizar esta avaliação um formulário sociodemográfico, um inventário de qualidade de vida em dermatologia (DQLI) e uma entrevista semiestruturada serão realizados em encontro único com os participantes da pesquisa. As doze voluntárias do estudo apresentam histórias de vida com intensos relatos de frustrações, impotência, insegurança, perdas, vergonha e solidão. O DQLI, utilizado para avaliação do impacto da AFF, na vida das voluntárias, foi coerente com as observações feitas pelas mesmas, de que a doença acompanha elevado grau de estresse e sofrimento

Hair plays an important role in human social and sexual communication. The androgen-stimulated, patterned loss of hair in cases of androgenetic alopecia (or common baldness) in genetically pre-disposed individuals, is associated with ageing and can cause marked phychological distress. However, it is poorly controlled. To investigate the effectiveness of daily topical application of a Chinese medicine-derived herbal mixture, Xiantene, on balding progression, two double-blind, placebo-controlled studies (3 and 12 months) were carried out on balding men using the trichogram approach. Xiantene significantly increased both the total number of hairs and those in anagen, improving the ratio of anagen:telogen hairs. This suggests that topical Xiantene increased the length of the anagen phase and may promote a cessation, or partial reversal, of the progression of androgenetic alopecia in men. Canities, loss of scalp hair colour, is another mark of ageing. To investigate whether early greying may protect follicles from androgenetic alopecia, the extent of alopecia, assessed using the Hamilton scale, was compared between men who first became grey before, or after, 30. Both alopecia and greying increased with age in 843 men (217 European, 626 Thai) whenever they first started greying. However, men who showed greying before 30 were significantly less bald, though more grey, in both groups. Hair follicle melanocytes synthesise the pigment melanin, producing reactive oxygen species (ROS) and oxidative stress; losing melanocyte pigmentary activity, and therefore these toxic factors, appears to enable hair follicles to maintain their full size for longer, despite the androgen drive to miniaturisation. / Tri-Mill Charitable Trust, Global Beauty International Management Ltd.

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This thesis examines representations of cancer in contemporary art, with a particular focus on unruly, un-idealized bodies at risk. In bringing together the discourses of art history and medicine, its aim is to engage conventions of visualizing cancer, and more importantly, to highlight the ways in which contemporary artists challenge dominant representations, re-imagining the cancerous body from an embodied perspective. Chapter One provides a context for images of cancer by examining an artistic account of how medicine constructs the body against an artists representation of her own cancerous body. Theorizing cancer as an abject condition, Chapter Two examines representational strategies for visualizing cancer that trouble distinctions between inside/outside, self/other, subject/object, healthy/diseased. Building on themes of gender, health, and identity, Chapter Three considers representations of chemotherapy-induced hair loss and baldness as the most visible signs of cancer, but highly unstable and performative ones that call the representational status of the disease into question. / History of Art, Design and Visual Culture