Faculty Bibliography

'Fat fingers' are thick digitate linear, curvilinear, branched, or oval/circular dermoscopic structures typically seen in seborrheic keratoses where they represent the gyri of their cerebriform surfaces. Their recognition is very useful in the diagnosis of these lesions, especially when the classic features (eg, milia, comedo-like openings) are absent. Histologically and by confocal microscopy the 'fat finger' gyri are accentuated by pigmented keratin filling the sulci. 'Fat fingers' must be differentiated from other linear structures such as 'network-like structures'; branched streaks; network; globules; pigmented ovoid-nests; and streaks/pseudopods seen in different melanocytic and non-melanocytic lesions

BACKGROUND: Function of the retinoblastoma tumor suppressor protein (pRB) may be compromised at a genetic level by gene loss or mutation or at a post-translational level by hyperphosphorylation. In this study, we examined adult soft tissue sarcomas (ASTS) to determine if alterations of pRB were associated with distinct patterns of pRB expression and clinical outcome. DESIGN: We investigated 86 ASTS patients using monoclonal antibodies that distinguish between hyperphosphorylated and underphosphorylated pRB products. We also used microsatellite analysis to investigate the genetic status of the RB locus. We correlated pRB alterations with proliferative activity, and with clinicopathological outcomes. RESULTS: Altered patterns of pRB expression are common in ASTS occurring in 84% of cases, and it is significantly associated with proliferative activity (p<0.001). Patients whose tumors either lack expression of pRB, or express hyperphosphorylated forms of pRB, have poor survivals compared to patients whose tumors exhibit a normal, underphosphorylated pattern of pRB expression (p=0.03). In addition, 63% of cases lacking expression of pRB showed loss-of-heterozygosity at the locus. CONCLUSIONS: Inactivation of pRB is common in adult STS, which may be due to either gene loss or post-translational modification, namely hyper-phosphorylation. Both mechanisms are associated with tumor cell proliferation and poor survival

The incidence and mortality rates of melanoma have risen for many decades in the United States. Increased exposure to ultraviolet (UV) radiation is generally considered to be responsible. Sunburns, a measure of excess sun exposure, have been identified as a risk factor for the development of melanoma. Because sunburns are primarily due to UVB (280-320 nm) radiation, UVB has been implicated as a potential contributing factor to the pathogenesis of melanoma. The adverse role of UVA (320-400 nm) in this regard is less well studied, and currently there is a great deal of controversy regarding the relationship between UVA exposure and the development of melanoma. This article reviews evidence in the English-language literature that surrounds the controversy concerning a possible role for UVA in the origin of melanoma. Our search found that UVA causes DNA damage via photosensitized reactions that result in the production of oxygen radical species. UVA can induce mutations in various cultured cell lines. Furthermore, in two animal models, the hybrid Xiphophorus fish and the opossum (Mondelphis domestica), melanomas and melanoma precursors can be induced with UVA. UVA radiation has been reported to produce immunosuppression in laboratory animals and in humans. Some epidemiologic studies have reported an increase in melanomas in users of sunbeds and sunscreens and in patients exposed to psoralen and UVA (PUVA) therapy. There is basic scientific evidence of the harmful effects of UVA on DNA, cells and animals. Collectively, these data suggest a potential role for UVA in the pathogenesis of melanoma. To date evidence from epidemiologic studies and clinical observations are inconclusive but seem to be consistent with this hypothesis. Additional research on the possible role of UVA in the pathogenesis of melanoma is required

BACKGROUND: The public has long been instructed to wear protective clothing against ultraviolet (UV) damage. OBJECTIVE: Our purpose was to determine the UV protection factor (UPF) of two cotton fabrics used in the manufacture of summer T-shirts and to explore methods that could improve the UPF of these fabrics. METHODS: Each of the two types of white cotton fabrics (cotton T-shirt and mercerized cotton print cloth) used in this study was divided into 4 treatment groups: (1) water-only (machine washed with water), (2) detergent-only (washed with detergent), (3) detergent-UV absorber (washed with detergent and a UV absorber), and (4) dyes (dyed fabrics). Ultraviolet transmission through the fabrics was measured with a spectrophotometer before and after laundry and dyeing treatments. Based on UV transmission through these fabrics, the UPF values were calculated. RESULTS: Before any treatments, the mean UPFs were 4.94 for the T-shirt fabric and 3.13 for the print cloth. There was greater UVA (320-400 nm) than UVB (280-320 nm) transmission through these fabrics. After 5 washings with water alone and with detergent alone, UPF increased by 51% and 17%, respectively, for the cotton T-shirt fabric. Washing the T-shirt fabrics with detergent plus the UV-absorbing agent increased the UPF by 407% after 5 treatments. Dyeing the fabric blue or yellow increased the UPF by 544% and 212%, respectively. Similar changes in UPFs were observed for the print cloth fabric. CONCLUSION: The two cotton fabrics used in this study offered limited protection against UV radiation as determined by spectrophotometric analysis. Laundering with detergent and water improves UPF slightly by causing fabric shrinkage. Dyeing fabrics or adding a UV-absorbing agent during laundering substantially reduces UV transmission and increases UPF. More UVA is transmitted through the fabrics than UVB

Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type