Yves Vander Haeghen

P-Cadherin Promotes Cell-Cell Adhesion and Counteracts Invasion in Human Melanoma

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 Ca2+-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.

Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?

Solitary café-au-lait spots are quite common in the general population but multiple café-au-lait macules (CALM) are often indicative of an underlying genetic disorder. The frequency of having more than five CALM is rare in normal individuals and is therefore considered as a cut-off for the diagnosis of neurofibromatosis type 1 (NF1). The etiopathogenesis of these macules is still very obscure. In this study we compared epidermal melanocyte and dermal mast cell numbers between four groups: control normal and control CALM skin, and NF1 normal and NF1 CALM skin and elaborated a possible role for stem cell factor (SCF) in CALM formation. The groups were analyzed by immunohistochemistry for numerical analysis of the melanocyte and mast cell population and by ELISA, western blot analysis and real-time quantitative PCR for further determination of the role of SCF. We found a significant increase in melanocyte density in NF1 CALM skin compared with the isolated CALM in control individuals. However, both groups displayed a similar increase in mast cell density. In addition, we found increased levels of soluble SCF in NF1 CALM and in NF1 normal fibroblast supernatant. We conclude that SCF is an important cytokine in NF1 skin, but that additional (growth) factors and/or genetic mechanisms are needed to induce NF1-specific CALM hyperpigmentation.

Subjective and Objective Evaluation of Noncultured Epidermal Cellular Grafting for Repigmenting Vitiligo

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.

Baerveldt glaucoma implants in the management of refractory glaucoma after vitreous surgery

Purpose:  To examine the effectiveness and safety of Baerveldt glaucoma implants in eyes with refractory glaucoma following vitrectomy.

Method to Measure Force Required to Remove Pediculus humanus capitis (Phthiraptera: Pediculidae) Eggs from Human Hair

Abstract Head lice are very common and mainly affect children between 3 and 12 yr old. Little is known about the way nits, the eggs of the head louse, are attached to the hair. In this report, an objective measurement procedure for the ease with which nits can be removed is presented. The first peak force, associated with the start of nit movement, and the average and maximal force during the sliding of the nit were measured. The three force variables correlated with the length of the cylinder by which the nit was attached to the hair. A negative correlation was found between the maximum force exerted and the distance of the nit from the scalp. The method described in this report can be used to determine the in vitro efficacy of various products to remove nits.

Psycho-visual evaluation of image quality attributes in digital pathology slides viewed on a medical color LCD display

We investigate the effects of common types of image manipulation and image degradation on the perceived image quality (IQ) of digital pathology slides. The reference images in our study were digital images of animal pathology samples (gastric fundic glands of a dog and liver of a foal) stained with haematoxylin and eosin. The following 5 types of artificial manipulations were applied to the images, each very subtle (though visually discernible) and always one at a time: blurring, gamma modification, adding noise, change in color saturation, and JPG compression. Three groups of subjects: pathology experts (PE), pathology students (PS) and imaging experts (IE), assessed 6 IQ attributes in 72 single-stimulus trials. The following perceptual IQ attribute ratings were collected: overall IQ, blur disturbance, quality of contrast, noise disturbance, and quality of color saturation. Our results indicate that IQ ratings vary quite significantly with expertise, especially, PE and IE tend to judge IQ according to different criteria. In particular, IE seem notably more sensitive to noise than PE who, on the other side, tend to be sensitive to manipulations in color and gamma parameters. It remains an important question for future research to examine the impact of IQ on the diagnostic performance of PE. That should support our present findings in suggesting directions for further development of the numerical IQ metrics for digital pathology data.

Consistent optical imaging and color measurement of the skin

We propose a small field-of-view color image acquisition system for the imaging and measurement of skin lesion and its properties in dermatology. The system consists of a 3 chip CCD camera, a frame grabber, a high-quality halogen annular light source and a pentium PC. The output images are in a standard device-dependent color space called sRGB or ITU-R BT.709 which has a known relation to the device-independent CIE XYZ color space and provides a fairly realistic view on a modern CRT- based monitor. In order to transform the images from the unknown and variable input RGB color space of the acquisition system to the sRGB space a profile of the acquisition system is determined based on 24 color targets with known properties. Determination of this profile is simple and quick, and it remains valid for many hours of operation (weeks or even months of normal use). Precision or reproducibility of the system is very good, both short-term (consecutive measurements) <(Delta) E*ab> equals 0.04 with (Delta) E*ab less than 0.1, medium-term (measurements under one profile but on different warm-up cycles) <(Delta) E*ab> equals 0.34 with (Delta) E*ab less than 1.2. Long-term precision (measurements under different profiles) is of the same order. Accuracy was evaluated for profiles based on different RGB to sRGB polynomial transforms computed both by linear least-squares in the sRGB space and by non-linear optimization in CIE L*a*b* color space. Results show that, using a set of test targets consisting of 15 paper color targets and 12 real measurements of human skin, the simple linear transform outperforms higher order polynomials and has <(Delta) E*ab> equals 6.53, with (Delta) E*ab less than 11.21. A small study of the pigmentation of the human skin after UV-radiation shows that when measuring areas of at least a few hundred pixels differences of more than 2 - 3 dE units are statistically significant.