Localization of Basic Fibroblast Growth Factor mRNA in Melanocytic Lesions by In Situ Hybridization

Basic fibroblast growth factor (bFGF) is a mitogen for normal human melanocytes and keratinocytes in culture. Experiments in vitro suggest that keratinocytes supply bFGF to melanocytes through a paracrine mechanism and that the aberrant expression of bFGF in melanomas confers growth independence from bFGF-producing cells. To determine whether bFGF is expressed in vivo, we examined a series of benign and malignant melanocytic lesions in situ using bFGF riboprobes on tissue sections, and correlated bFGF expression with histologic phenotype. Seventeen melanocytic neoplasms were studied, including four common acquired nevi, four dysplastic nevi, four primary malignant melanomas, and five metastatic melanomas. Nevic cells in benign intradermal nevi showed low signal intensity (1+), whereas compound and dysplastic nevi showed 2+ to 3+ expression in the junctional nevic cell population and 1+ expression in the dermal nevic cell population. Melanocytes in primary melanomas had intermediate (2+) and those in metastatic melanomas had low (1+) levels of bFGF gene transcripts. Fibroblasts expressed high levels (3+) and epidermal and adnexal keratinocytes moderate (2+) levels of bFGF in all cases studied. Basic PGF expression in endothelial cells, known to produce and respond to this growth factor in vitro, was lower than that in the fibroblast and keratinocyte cell population and, in 10 of 17 cases, no bFGF mRNA was detectable. This study shows that bFGF is expressed in nevomelanocytes in vivo in all melanocytic lesions studied and thus cannot be used as a marker for transformation. The presence of bFGF gene transcripts in the various dermal cell types and in keratinocytes suggests that it may act as an autocrine and paracrine growth factor in regulating cellular proliferation in the skin

Next Generation Skills and Leaders: Future Proofing UWA Library

The shifting sands and rising tides of digital disruption within academic libraries, and the continually evolving demands and expectations of university leaders, academics and students, require innovative solutions and effective leadership. In 2018, the Library at the University of Western Australia (UWA) commenced two initiatives to future proof its workforce, preparing staff to take advantage and innovate within the rapid pace of change. Leading for Success is a leadership program designed to provide library staff with a contemporary and relevant skill-set to initiate and lead change to develop and deliver new initiatives. This program builds on a strong history of successful leadership development at UWA Library. Designed and delivered in partnership with UWA’s Organisational Development unit, the University Library is leading the way through the creation of a program that can be adapted and delivered into other areas of the University. The program aims to prepare staff for new challenges and opportunities, including higher-level positions, which contributes to succession planning within the Library and the wider University. In 2018, the Library also commenced a project to develop a workforce plan to identify current and near-future skills required for library staff. This has resulted in the production of a dynamic skills matrix for use as a tool for mapping current staff capabilities and to assist with professional developmental planning for individual staff and teams. The plan is assisting the Library to future proof its workforce and enable staff to engage proactively in career development. This paper will describe the elements of the two programs and make comparisons with library staff development initiatives delivered elsewhere. It will evaluate the success of the two programs from the perspective of the participants, and provide a framework for other institutions wishing to develop similar initiatives

Cutaneous metastasis from penile squamous cell carcinoma resembling carcinoma en cuirasse

Penile squamous cell carcinoma is a rare malignancy seen more frequently in developing nations. Metastasis occurs in a predictable manner, with superficial lymph node involvement occurring first, followed by deep lymph node involvement, and then distant spread. Brain, lung, liver, and bone are the typical sites of distant metastasis. We present the unusual case of an 81-year-old man with penile squamous cell carcinoma requiring total penectomy who developed a confluent red to violaceous, indurated suprapubic plaque with satellite papules and bulky inguinal lymphadenopathy. The shield-like clinical presentation and infiltrating strands and cords on histology resembled carcinoma en cuirasse, a rare form of cutaneous metastasis frequently associated with breast cancer but not reported with penile squamous cell carcinoma

GPR56 Regulates VEGF Production and Angiogenesis during Melanoma Progression

2012 February 15Angiogenesis is a critical step during cancer progression. The VEGF is a major stimulator for angiogenesis and is predominantly contributed by cancer cells in tumors. Inhibition of the VEGF signaling pathway has shown promising therapeutic benefits for cancer patients, but adaptive tumor responses are often observed, indicating the need for further understanding of VEGF regulation. We report that a novel G protein–coupled receptor, GPR56, inhibits VEGF production from the melanoma cell lines and impedes melanoma angiogenesis and growth, through the serine threonine proline-rich segment in its N-terminus and a signaling pathway involving protein kinase Cα. We also present evidence that the two fragments of GPR56, which are generated by autocatalyzed cleavage, played distinct roles in regulating VEGF production and melanoma progression. Finally, consistent with its suppressive roles in melanoma progression, the expression levels of GPR56 are inversely correlated with the malignancy of melanomas in human subjects. We propose that components of the GPR56-mediated signaling pathway may serve as new targets for antiangiogenic treatment of melanoma. Cancer Res; 71(16); 5558–68.National Institutes of Health (U.S.) (U54CA126515)Howard Hughes Medical Institut

Outbreak of Mycobacterium chelonae Infection Associated with Tattoo Ink

Background In January 2012, on the basis of an initial report from a dermatologist, we began to investigate an outbreak of tattoo-associated Mycobacterium chelonae skin and softtissue infections in Rochester, New York. The main goals were to identify the extent, cause, and form of transmission of the outbreak and to prevent further cases of infection. Methods We analyzed data from structured interviews with the patients, histopathological testing of skin-biopsy specimens, acid-fast bacilli smears, and microbial cultures and antimicrobial susceptibility testing. We also performed DNA sequencing, pulsed-field gel electrophoresis (PFGE), cultures of the ink and ingredients used in the preparation and packaging of the ink, assessment of source water and faucets at tattoo parlors, and investigation of the ink manufacturer. Results Between October and December 2011, a persistent, raised, erythematous rash in the tattoo area developed in 19 persons (13 men and 6 women) within 3 weeks after they received a tattoo from a single artist who used premixed gray ink; the highest occurrence of tattooing and rash onset was in November (accounting for 15 and 12 patients, respectively). The average age of the patients was 35 years (range, 18 to 48). Skin-biopsy specimens, obtained from 17 patients, showed abnormalities in all 17, with M. chelonae isolated from 14 and confirmed by means of DNA sequencing. PFGE analysis showed indistinguishable patterns in 11 clinical isolates and one of three unopened bottles of premixed ink. Eighteen of the 19 patients were treated with appropriate antibiotics, and their condition improved. Conclusions The premixed ink was the common source of infection in this outbreak. These findings led to a recall by the manufacturer

Diaspora identification and long-distance nationalism among Tamil migrants of diverse state origins in the UK

Accounts of Tamil long-distance nationalism have focused on Sri Lankan Tamil migrants. But the UK is also home to Tamils of non-Sri Lankan state origins. While these migrants may be nominally incorporated into a 'Tamil diaspora', they are seldom present in scholarly accounts. Framed by Werbner's (2002) conception of diasporas as 'aesthetic' and 'moral' communities, this article explores whether engagement with a Tamil diaspora and long-distance nationalism is expressed by Tamil migrants of diverse state origins. While migrants identify with an aesthetic community, 'membership' of the moral community is contested between those who hold direct experience of suffering as central to belonging, and those who imagine the boundaries of belonging more fluidly - based upon primordial understandings of essential ethnicity and a narrative of Tamil 'victimhood' that incorporates experiences of being Tamil in Sri Lanka, India and in other sites, despite obvious differences in these experiences. © 2013 Taylor & Francis

Defective Cell Cycle Checkpoint Functions in Melanoma Are Associated with Altered Patterns of Gene Expression

Defects in DNA damage responses may underlie genetic instability and malignant progression in melanoma. Cultures of normal human melanocytes (NHMs) and melanoma lines were analyzed to determine whether global patterns of gene expression could predict the efficacy of DNA damage cell cycle checkpoints that arrest growth and suppress genetic instability. NHMs displayed effective G1 and G2 checkpoint responses to ionizing radiation-induced DNA damage. A majority of melanoma cell lines (11/16) displayed significant quantitative defects in one or both checkpoints. Melanomas with B-RAF mutations as a class displayed a significant defect in DNA damage G2 checkpoint function. In contrast the epithelial-like subtype of melanomas with wild-type N-RAS and B-RAF alleles displayed an effective G2 checkpoint but a significant defect in G1 checkpoint function. RNA expression profiling revealed that melanoma lines with defects in the DNA damage G1 checkpoint displayed reduced expression of p53 transcriptional targets, such as CDKN1A and DDB2, and enhanced expression of proliferation-associated genes, such as CDC7 and GEMININ. A Bayesian analysis tool was more accurate than significance analysis of microarrays for predicting checkpoint function using a leave-one-out method. The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo