Malignant transformation of melanocytes frequently coincides with alterations in epithelial cadherin (E-cadherin) expression, switching on of neural cadherin (N-cadherin), and, when progressed to a metastatic stage, loss of membranous placental cadherin (P-cadherin). In vitro studies of melanoma cell lines have shown invasion suppressor and promoter roles for E-cadherin and N-cadherin, respectively. In the present study, we investigated the effect of P-cadherin on aggregation and invasion using melanoma cells retrovirally transduced with human P-cadherin. De novo expression of P-cadherin in P-cadherin-negative cell lines (BLM and HMB2) promoted cell-cell contacts and Ca 2+ -dependent cell-cell aggregation in two-and three-dimensional cultures, whereas it counteracted invasion. These effects were not observed following P-cadherin transduction of endogenously P-cadherin-positive MeWo cells. In addition, P-cadherin-transduced BLM cells coaggregated with keratinocytes and showed markedly reduced invasion in a reconstructed skin model. The proadhesive and anti-invasive effects of P-cadherin were abolished on targeted mutation of its intracellular juxtamembrane domain or its extracellular domain. For the latter mutation, we mimicked a known missense mutation in P-cadherin (R503H), which is associated with congenital hypotrichosis with juvenile macular dystrophy. (Cancer Res 2005; 65(19): 8774-83)
Abstract-We propose a novel imaging system useful in dermatology, more precisely for the follow-up of patients with an increased risk of skin cancer. The system consists of a Pentium PC equipped with a RGB frame grabber, a 3-chip CCD camera controlled by the serial port and equipped with a zoom lens and a halogen annular light source.Calibration of the imaging system provides a way to transform the acquired images, which are defined in an unknown color space, to a standard well-defined color space called sRGB. sRGB has a known relation to the CIE 1 XYZ and CIE L * a * b * colorimetric spaces. These CIE color spaces are based on the human vision, and allow the computation of a color difference metric called CIE ∆E * ab , which is proportional to the color difference as seen by a human observer. Several types of polynomial RGB to sRGB transforms will be tried, including some optimized in perceptually uniform color spaces. The use of a standard and well-defined color space also allows meaningful exchange of images, e.g. in teledermatology.The calibration procedure is based on 24 patches with known color properties, and takes about 5 minutes to perform. It results in a number of settings called a profile which remains valid for tens of hours of operation. Such a profile is checked prior to acquiring images using just one color patch, and is adjusted on the fly to compensate for short-term drift in the response of the imaging system. Precision or reproducibility of subsequent color measurements is very good with ∆E * ab = 0.3 and ∆E * ab < 1.2. Accuracy compared to spectrophotometric measurements is fair with ∆E * ab = 6.2 and ∆E * ab < 13.3.
Mutations of the gene encoding myosin V can produce a dilute or silvery hair color and various neurologic defects in mice and patients with Griscelli syndrome, leading to speculations that the myosin V motor protein plays a critical role in transporting melanosomes within melanocytes and neurosecretory vesicles within neurons. Therefore, we investigated the in vitro expression of myosin V in cultured normal human melanocytes, keratinocytes, and dermal fibroblasts using reverse transcriptase-polymerase chain reaction and northern blot analysis. Subcellular distribution of myosin V and proximity to actin bundles and melanosomes were determined by double indirect immunofluorescence labeling and immunogold electron microscopy. In all studied cells myosin V is expressed and treatment of melanocytes with the cyclic AMP-inducer 3-isobutyl-1-methylxanthine causes an induction of the myosin V message. In all cells myosin V colocalizes with actin bundles, concentrating in the subcortical cell zone. In the melanocyte it is closely associated with melanosomes. Quantitative analysis of myosin V labeling in melanocytes reveals a significantly higher (p < 0.005) presence of myosin V in the periphery of dendrites. These results suggest that myosin V is important in melanosome transport in human melanocytes. Possible roles in the other skin cells remain to be elucidated.
Background: Noncultured epidermal cell transplantation in vitiligo permits the coverage of relatively large areas without culturing cells. Objective: To investigate the effectiveness of noncultured epidermal cell transplantation in treating stabilized vitiligo using objective and subjective evaluation methods. Methods: Noncultured autologous melanocytes and keratinocytes were grafted in a hyaluronic-acid-enriched suspension on superficially laser-abraded vitiligo lesions in 40 patients with refractory stable vitiligo (30 with generalized and 10 with localized vitiligo). The repigmentation was evaluated 3–12 months after grafting using a digital image analysis system. Furthermore the treatment was evaluated from the patients’ point of view with the DLQI (Dermatology Life Quality Index) and a ‘global assessment’. Results: The mean percentage of repigmentation, evaluated at the last follow-up visit, was 72% (median 84%), and a repigmentation of ≧70% was observed in 62% of patients. The best results were achieved in the neck and the presternal region. A subjective evaluation was performed in half of the subjects. The mean DLQI score at inclusion (6.95, SD = 6.68, n = 20) was significantly decreased after treatment (p = 0.013, mean 3.85, SD = 4.13, n = 20). The patients were satisfied with the achieved result, found it worthwhile to undergo the treatment and would choose it again. Conclusion: According to both subjective and objective evaluation methods, noncultured epidermal cell transplantation is promising in patients with stable vitiligo.
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