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PDF file, 48K, PCR primers used in study.

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PDF file, 3359K, Effect of Epim on ductal length, terminal endbuds, and lobuloalveolar structure formation.

PDF file, 845K, Epim overexpression leads to enlargement of organoid cyst and upregulation of Pgr during bud formation.

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Epimorphin/syntaxin-2 is a membrane-tethered protein localized extracellularly (Epim) and intracellularly (Stx-2). The extracellular form Epim stimulates morphogenic processes in a range of tissues, including in murine mammary glands where its overexpression in luminal epithelial cells is sufficient to drive hyperplasia and neoplasia. We analyzed WAP-Epim transgenic mice to gain insight into how Epim promotes malignancy. Ectopic overexpression of Epim during postnatal mammary gland development led to early side-branching onset, precocious bud formation, and increased proliferation of mammary epithelial cells. Conversely, peptide-based inhibition of Epim function reduced side branching. Because increased side branching and hyperplasia occurs similarly in mice upon overexpression of the progesterone receptor isoform-a (Pgr-a), we investigated whether Epim exhibits these phenotypes through Pgr modulation. Epim overexpression indeed led to a steep upregulation of both total Pgr mRNA and Pgr-a protein levels. Notably, the Pgr antagonist RU486 abrogated Epim-induced ductal side branching, mammary epithelial cell proliferation, and bud formation. Evaluation of Epim signaling in a three-dimensional ex vivo culture system showed that its action was dependent on binding to its extracellular receptor, integrin-αV, and on matrix metalloproteinase 3 activity downstream of Pgr-a. These findings elucidate a hitherto unknown transcriptional regulator of Pgr-a, and shed light on how overexpression of Epim leads to malignancy. Cancer Res; 73(18); 5719–29. ©2013 AACR.

Background Leprosy is a chronic infection of the skin and peripheral nerves caused by the bacterium Mycobacterium leprae, which causes peripheral insensitivity and disfigurements of the skin, limbs, and digits. Social stigma is a common consequence of leprosy and may differ according to level of physical disfigurement and geographic location. The objective of this study was to assess social stigma encountered by patients with leprosy in clinical settings located in rural Tanzania and urban USA and to compare the social stigma reported in these regions. Methods A total of 56 respondents were recruited from one leprosy inpatient facility in Shirati, Tanzania (n = 28), and one outpatient clinic in Los Angeles, USA (n = 28). Cross-sectional data were obtained from face-to-face interviews, which were conducted with respondents at each clinic location. Measures of perceived stigma were assessed in family relationship, vocational, social interaction, and interpersonal contexts. Results Patients in Tanzania, as compared with those in the USA, reported significantly higher levels of stigma in family relationship and vocational contexts. Tanzanian patients also reported higher levels of stigma in social interaction and self-esteem contexts, but these differences were marginally significant and may reflect the small sample size. Conclusions Leprosy-related social stigma is a major problem in regions of both developed and developing countries; however, patients with leprosy in developing countries reported higher levels of stigma in four social contexts. A public health role in dermatology is discussed as an agent of early diagnosis, control, and education in order to reduce social stigma and promote social rehabilitation.

Background: Visible skin disorders can limit healthy psychosocial development in several domains owing to the stigma these disorders create. Objective: To assess if emerging adults with acne and eczema perceive stigma in diverse developmental domains resulting from their visible skin conditions. Methods: A convenience sample of 336 emerging adults attending a diverse public university in northern California completed a Web-based survey. Multivariate modeling was used to determine if eczema and acne result in perceived stigma. Results: The mean (SD) age of respondents was 20.1(1.5) years; most were white (43.2%) and female (62.5%). Almost half (47%) reported acne and 16.4% reported eczema. The likelihood of experiencing perceived stigma was 1.6 (95% CI 1.13–2.27, p < .001) times higher for those with eczema compared to those without eczema, and the likelihood of experiencing perceived stigma was 3.19 (95% CI 2.41–4.22, p < .0001) times higher for those with acne compared to those without acne. Conclusions: Our findings indicate that emerging adults perceive stigma as a result of their acne and eczema in several important developmental domains. The results suggest that acne may have a stronger relationship with perceived stigma than eczema, perhaps owing to its greater visibility on the body. University-based activities are recommended to support those with skin disease.

Leprosy is a chronic infection of the skin and peripheral nerves caused by the bacterium Mycobacterium leprae, which causes peripheral insensitivity and disfigurements of the skin, limbs, and digits. Social stigma is a common consequence of leprosy and may differ according to level of physical disfigurement and geographic location. The objective of this study was to assess social stigma encountered by patients with leprosy in clinical settings located in rural Tanzania and urban USA and to compare the social stigma reported in these regions. A total of 56 respondents were recruited from one leprosy inpatient facility in Shirati, Tanzania (n = 28), and one outpatient clinic in Los Angeles, USA (n = 28). Cross-sectional data were obtained from face-to-face interviews, which were conducted with respondents at each clinic location. Measures of perceived stigma were assessed in family relationship, vocational, social interaction, and interpersonal contexts. Patients in Tanzania, as compared with those in the USA, reported significantly higher levels of stigma in family relationship and vocational contexts. Tanzanian patients also reported higher levels of stigma in social interaction and self-esteem contexts, but these differences were marginally significant and may reflect the small sample size. Leprosy-related social stigma is a major problem in regions of both developed and developing countries; however, patients with leprosy in developing countries reported higher levels of stigma in four social contexts. A public health role in dermatology is discussed as an agent of early diagnosis, control, and education in order to reduce social stigma and promote social rehabilitation.

Dermatological conditions are observed in an estimated 90% or more of all HIV infected people worldwide. Microbial infections, inflammatory conditions and neoplasms are the three main causes for the development of dermatological findings in HIV patients. A total of 276 HIV patients were examined by a dermatologist to identify skin, hair and nail pathologies. CD4 count was measured; Liver function test (LFT) and complete blood count (CBC) were also done. Skin biopsies were obtained and sent for pathological study. Analysis showed 90 (32.6%) of patients had at least one identifiable dermatological ailment. The most common dermatologic manifestations were dermatitis (22.3%), seborrheic dermatitis (13.8%), folliculitis (6.7%), dermatophytosis (6.7%), oral candidiasis (6.7%), warts (6.7%) and Herpes Zoster (3.6%). CD4 count was positively and significantly associated with occurrence of a dermatologic manifestation. Moreover, the type of antiretroviral drug was correlated with these manifestations. Due to high prevalence of skin diseases, severity of complications and overall influence on the patient’s quality of life, considerations should be given to timely diagnosis and treatment of dermatologic complications among HIV/AIDS patients. Key words: Dermatologic, HIV/AIDS, prevalence.

A number of recent studies identified nuclear factors that together have the unique ability to induce pluripotency in differentiated cell types. However, little is known about the factors that are needed to maintain human embryonic stem (ES) cells in an undifferentiated state. In a search for such requirements, we performed a comprehensive meta-analysis of publicly available SAGE and microarray data. The rationale for this analysis was to identify genes that are exclusively expressed in human ES cell lines compared to 30 differentiated tissue types. The WNT receptor FZD7 was found among the genes with an ES cell-specific expression profile in both SAGE and microarray analyses. Subsequent validation by quantitative RT-PCR and flow cytometry confirmed that FZD7 mRNA levels in human ES cells are up to 200-fold higher compared to differentiated cell types. ShRNA-mediated knockdown of FZD7 in human ES cells induced dramatic changes in the morphology of ES cell colonies, perturbation of expression levels of germ layer-specific marker genes, and a rapid loss of expression of the ES cell-specific transcription factor OCT4. These findings identify the WNT receptor FZD7 as a novel ES cell-specific surface antigen with a likely important role in the maintenance of ES cell self-renewal capacity.

This commentary raises an important issue that has not been sincerely considered in the field of dermatology, which is the vital role of hairdressers--a group that makes daily observations of the general populations' scalp and neck--in the detection of head and neck melanomas in the general population. We note several key areas of research that are needed to assess the feasibility of using hairdressers as a resource for melanoma detection and referral. If research suggests hairdressers can be trained and are willing to make appropriate referrals then implementing these efforts will likely reduce the increasing disease burden of head and neck melanomas.