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Though skin fibroblasts (FB) are the main cell population within the dermis, the different skin FB subsets are not well characterized and the traditional classification into reticular and papillary FBs has little functional relevance. To fill the gap of knowledge on FB diversity in human skin, we performed single-cell RNA sequencing. Investigation of marker genes for the different skin cell subtypes revealed a heterogeneous picture of FBs. When mapping reticular and papillary FB markers, we could not detect cluster specificity, suggesting that these two populations show a higher transcriptional heterogeneity than expected. This finding was further confirmed by in situ hybridization, showing that DPP4 was expressed in both dermal layers. Our analysis identified six FB clusters with distinct transcriptional signatures. Importantly, we could demonstrate that in human skin DPP4+ FBs are the main producers of factors involved in extracellular matrix (ECM) assembly. In conclusion, we provide evidence that hitherto considered FB markers are not ideal to characterize skin FB subpopulations in single-cell sequencing analyses. The identification of DPP4+ FBs as the main ECM-producing cells in human skin will foster the development of anti-fibrotic treatments for the skin and other organs.

We have reported recently that inactivation of the essential autophagy-related gene 7 (Atg7) in keratinocytes has little or no impact on morphology and function of the epidermal barrier in experimental animals. When these mice aged, mutant males, (Atg7 ΔKC), developed an oily coat. As the keratin 14 promoter driven cre/LoxP system inactivates floxed Atg7 in all keratin 14 (K14) expressing cells, including sebocytes, we investigated whether the oily hair phenotype was the consequence of changes in function of the skin sebaceous glands. Using an antibody to the GFP-LC3 fusion protein, autophagosomes were detected at the border of sebocyte disintegration in control but not in mutant animals, suggesting that autophagy was (a) active in normal sebaceous glands and (b) was inactivated in the mutant mice. Detailed analysis established that dorsal sebaceous glands were about twice as large in all Atg7 ΔKC mice compared to those of controls (Atg7 F/F), and their rate of sebocyte proliferation was increased. In addition, male mutant mice yielded twice as much lipid per unit hair as age-matched controls. Analysis of sebum lipids by thin layer chromatography revealed a 40% reduction in the proportion of free fatty acids (FFA) and cholesterol, and a 5-fold increase in the proportion of fatty acid methyl esters (FAME). In addition, the most common diester wax species (58-60 carbon atoms) were increased, while shorter species (54-55 carbon atoms) were under-represented in mutant sebum. Our data show that autophagy contributes to sebaceous gland function and to the control of sebum composition.

PSORS1C2 is a gene located between coiled-coil alpha-helical rod protein 1 (CCHCR1) and corneodesmosin (CDSN) within the psoriasis susceptibility locus 1 (PSORS1). Here, we performed a comparative genomics analysis of the as-yet incompletely characterized PSORS1C2 gene and determined its expression pattern in human tissues. In contrast to CCHCR1, which is common to all vertebrates investigated, PSORS1C2 and CDSN are present exclusively in mammals, indicating that the latter genes have originated after the evolutionary divergence of mammals and reptiles. CDSN is conserved in aquatic mammals, whereas PSORS1C2 orthologs contain gene-inactivating frame shift mutations in whales and dolphins, in which the epidermal differentiation programme has degenerated. Reverse-transcription PCR screening demonstrated that, in human tissues, PSORS1C2 is expressed principally in the epidermis and weakly in the thymus. PSORS1C2 mRNA was strongly upregulated during terminal differentiation of human keratinocytes in vitro. Immunohistochemistry revealed exclusive expression of PSORS1C2 in the granular layer of the epidermis and in cornifying epithelial cells of Hassall's corpuscles of the thymus. In summary, our results identify PSORS1C2 as a keratinocyte cornification-associated protein that has originated in evolutionarily basal mammals and has undergone gene inactivation in association with the loss of the skin barrier function in aquatic mammals.

Senescent cells accumulate during ageing in various tissues and contribute to organismal ageing. However, factors that are involved in the induction of senescence in vivo are still not well understood. SNEV(P) (rp19/) (PSO) (4) is a multifaceted protein, known to be involved in DNA damage repair and senescence, albeit only in vitro. In this study, we used heterozygous SNEV(+/-) mice (SNEV-knockout results in early embryonic lethality) and wild-type littermate controls as a model to elucidate the role of SNEV(P) (rp19/) (PSO) (4) in DNA damage repair and senescence in vivo. We performed PUVA treatment as model system for potently inducing cellular senescence, consisting of 8-methoxypsoralen in combination with UVA on mouse skin to induce DNA damage and premature skin ageing. We show that SNEV(P) (rp19/) (PSO) (4) expression decreases during organismal ageing, while p16, a marker of ageing in vivo, increases. In response to PUVA treatment, we observed in the skin of both SNEV(P) (rp19/) (PSO) (4) and wild-type mice an increase in γ-H2AX levels, a DNA damage marker. In old SNEV(P) (rp19/) (PSO) (4) mice, this increase is accompanied by reduced epidermis thickening and increase in p16 and collagenase levels. Thus, the DNA damage response occurring in the mouse skin upon PUVA treatment is dependent on SNEV(P) (rp19/) (PSO) (4) expression and lower levels of SNEV(P) (rp19/) (PSO) (4) , as in old SNEV(+/-) mice, result in increase in cellular senescence and acceleration of premature skin ageing.

ZusammenfassungHintergrund und Ziele: Matriptase-1 wesentlich an der terminalen Differenzierung von Keratinozyten (KC) beteiligt. In einer fruheren Studie konnten zeigen, dass der knockdown der Matriptase-1 Expression in organotypischen Hautkulturen zu einer Beeintrachtigung der KC-Differenzierung und zur Retention von Zellkernen im Stratum corneum fuhrt. In dieser Studie untersuchten wirdie Expression und Regulation der Matriptase-1 in psoriatischer Haut und primaren humanen KC in vitro. Patienten und Methoden: Mittels Western-Blot Analyse, Immunfluoreszenzfarbung, qRT-PCR und Aktivitats-Assays wurde die Expression von Matriptase-1 in ­gesunder und psoriatischer Haut und ihre Regulation in organotypischen Hautkulturen analysiert. Durch adenovirale Uberexpression einer dominant negativen Form von IKK2 wurde die Beteiligung des Nuclear factor kappa B (NFκB)-Signalweges ­untersucht. Ergebnisse: Ingesunder menschlicher Haut und in organotypischen Hautkulturen wurde eine signifikante Matriptase-1 Expression ausschlieslich im Stratum granulosum nachgewiesen. In lasionaler Haut von Psoriasispatienten waren sowohl die Expression als auch die Aktivitat von Matriptase-1 stark reduziert. Die Zugabe von TNFα zu organotypischen Kulturen fuhrte zum vollstandigen Verlust der Matriptase-1-Expression und einer gestorten KC-Differenzierung. Weiters konnten wir zeigen, dass die TNFα-induzierte Herabregulation von Matriptase-1 uber die Aktivierung des IKK2/NFκB-Signalweges reguliert wird. Schlussfolgerungen: Da Matriptase-1 an der terminalen KC-Differenzierung beteiligt ist, tragt ihr Fehlen in psoriatischen Hautlasionen vermutlich zu der gestorten Barrierefunktion dieser Krankheit bei. Unsere Daten weisen darauf hin, dass eine Blockade des IKK2/NFκB-Signalweges ein interessanter Ansatz fur die Behandlung von Psoriasis sein konnte.

Objectives Ageing leads to characteristic changes in the appearance of facial skin. Among these changes, we can distinguish the skin topographic cues (skin sagging and wrinkles), the dark spots and the dark circles around the eyes. Although skin changes are similar in Caucasian and Chinese faces, the age of occurrence and the severity of age-related features differ between the two populations. Little is known about how the ageing of skin influences the perception of female faces in Chinese women. The aim of this study is to evaluate the contribution of the different age-related skin features to the perception of age and attractiveness in Chinese women. Methods Facial images of Caucasian women and Chinese women in their 60s were manipulated separately to reduce the following skin features: (i) skin sagging and wrinkles, (ii) dark spots and (iii) dark circles. Finally, all signs were reduced simultaneously (iv). Female Chinese participants were asked to estimate the age difference between the modified and original images and evaluate the attractiveness of modified and original faces. Results Chinese women perceived the Chinese faces as younger after the manipulation of dark spots than after the reduction in wrinkles/sagging, whereas they perceived the Caucasian faces as the youngest after the manipulation of wrinkles/sagging. Interestingly, Chinese women evaluated faces with reduced dark spots as being the most attractive whatever the origin of the face. The manipulation of dark circles contributed to making Caucasian and Chinese faces being perceived younger and more attractive than the original faces, although the effect was less pronounced than for the two other types of manipulation. Conclusion This is the first study to have examined the influence of various age-related skin features on the facial age and attractiveness perception of Chinese women. The results highlight different contributions of dark spots, sagging/wrinkles and dark circles to their perception of Chinese and Caucasian faces. Résumé Objectifs Le vieillissement entraine des changements caractéristiques de l'apparence de la peau du visage. Parmi ces changements on distingue les éléments topographiques (relâchement de la peau et rides), les taches brunes et les cernes sur le contour de l'œil. Bien que ces modifications cutanées avec l'âge soient similaires pour les visages caucasiens et chinois; leur âge d'apparition et leur degré de sévérité varient entre ces deux populations. Il y a très peu d'informations disponibles liées à l'influence du vieillissement cutané sur la perception des visages féminins par les femmes chinoises. L'objectif de cette étude est d'évaluer la contribution des différents signes de vieillissement à la perception de l'âge et d'attirance chez ces femmes. Methodes Des photos de visages de femmes caucasiennes et chinoises d'environ 60 ans ont été manipulées de façon à réduire séparément les signes suivants: (i) le relâchement de la peau et les rides, (ii) les taches brunes, et (iii) les cernes. Enfin, tous les signes ont été atténués ensemble (iv). Des participantes chinoises ont estimé, à partir de ces photos, l'écart d'âge entre la version originale et chaque version modifiée; elles ont également évalué l'attirance des visages originaux et modifiés. Resultats Les femmes chinoises ont jugé les visages chinois plus jeunes après correction des taches qu'après correction des rides/relâchement, alors que les visages caucasiens ont été perçus les plus jeunes après correction des rides/relâchement. Les femmes chinoises ont jugé que les visages avec correction des taches étaient les plus attirants quelle que soit l'origine du visage. La manipulation des cernes a entraîné un rajeunissement des 2 types de visages et les a rendus plus attirants, même si l'effet observé était moindre que pour les autres corrections. Conclusion Il s'agit de première étude qui examine l'influence de plusieurs signes de vieillissement cutanés sur la perception de l'âge et de l'attirance des visages par les femmes chinoises. Les résultats mettent en évidence que les taches, les rides/relâchement et les cernes contribuent différemment à leur perception des visages chinois et caucasiens.

In normal skin, tightly connected keratinocytes in the stratum granulosum and terminally differentiated keratinocytes in the stratum corneum build an efficient barrier that inhibits extensive water loss while simultaneously preventing the entry of microbial pathogens and allergens into the skin (1). Dysregulation of keratinocyte differentiation together with pathologic changes in this natural barrier function is commonly associated with skin diseases such as atopic dermatitis, psoriasis, and ichthyosis vulgaris (2–4). Recently, loss-of-function mutations in the filaggrin gene have been identified (5, 6). These mutations not only impair the normal formation of the skin barrier, but also decrease the production of endogenous moisturizing molecules that lead to reduced stratum corneum hydration (4, 7). However, besides genetic defects of filaggrin production, other factors play a role in the pathogenesis of atopic dermatitis and the associated skin barrier defects as indicated by several observations: (i) The majority of individuals with atopic dermatitis do not exhibit null mutations in the filaggrin gene (8), (ii) individuals with atopic dermatitis without mutations in the filaggrin gene may also develop severe skin barrier defects (9), and (iii) a significant fraction of individuals carrying double-allele loss-of-function mutations in the filaggrin gene do not develop atopic dermatitis (4, 10). In line with this concept, it was shown recently that the pro-inflammatory cytokines interleukin-4 (IL-4), IL-31, and TNF-α compromise barrier function (11) and modulate the expression of differentiation-associated proteins in keratinocytes (12–14). Mast cells are present in normal skin, and increased numbers of mast cells are regularly observed in the skin of patients with atopic dermatitis even before the onset of inflammation (4, 15). Mast cells release a number of important signaling molecules, among which histamine has particularly potent pro-inflammatory activities (16). After mast cell degranulation, histamine concentrations within the tissue can rise to 10–1000 μM (17), and increased histamine levels have been reported for lesional and nonlesional skin of patients with atopic dermatitis (18). A role of endogenous histamine in the modulation of keratinocyte maturation has been suggested previously based on the observation that antihistamines have a beneficial effect on skin barrier recovery after tape striping in normal mouse skin (19). In the present study, we address the impact of histamine on the differentiation of human keratinocytes in different in vitro systems, among them a three-dimensional organotypic human skin model. This skin model has been shown previously to resemble native human skin, especially with regard to skin development and keratinocyte differentiation (20, 21). Our findings show that histamine prevents the expression of late differentiation antigens in keratinocytes and strongly decreases the expression of tight junction and desmosomal proteins, leading to the formation of a defective skin barrier.

Background To date, few epidemiological data on the relationships between solar lentigines, freckles and behavioural and constitutional risk factors in Caucasian populations exist. Objectives To investigate the potential impact of behavioural and phenotypic variables, as well as the MC1R genetic background, on the history of facial freckles and the severity of solar lentigines in Caucasian women. Methods The severity of solar lentigines was graded from facial digital images of 523 French middle-aged women by a dermatologist and summarized by a score afterwards. The history of facial freckles was assessed and the sun-exposure behaviour was characterized using a six-category typology. Risk factors including MC1R polymorphism were evaluated using logistic regression models. Results Two constitutive host factors were found to be independently associated with a history of facial freckles: frequent sunburns and the presence of diminished function variants of the MC1R gene. In addition to age, five factors were independently associated with solar lentigines: constitutive host factors (dark skin colour and tanning capacity), a history of freckles, sun-exposure behaviour and current intake of oral contraceptive or progestogen treatments. Conclusion These results strengthen the hypothesis that solar lentigines are markers of photoaging, whereas freckles are mainly determined by genetic factors. The finding that hormonal treatment is associated with a higher risk for solar lentigines merits further investigations.

Background Atopic dermatitis (AD) is associated with null mutations in the filaggrin (FLG) gene. Objective To assess the impact of FLG null mutations on biophysical properties and the molecular composition of the stratum corneum (SC) in healthy individuals and AD patients. Methods A total of 196 French adults, including 97 with a history of mild to moderate AD, were genotyped for the three major European FLG mutations. Components of the natural moisturizing factor (NMF), lipids and water content in the SC were determined using Raman spectroscopy. In addition, trans-epidermal water loss, capacitance and pH of the SC were measured. Results Stratum corneum concentrations of total NMF, water, ornithine and urocanic acid (UCA) were significantly lower in AD patients than in healthy controls. Null mutations of FLG were detected in 4% of controls and 10% of AD patients. FLG mutations were associated with increased SC levels of lactate, reduced concentrations of most other NMF components and higher disease severity in AD patients. In AD patients without FLG mutations, the content of NMF constituents decreased with increasing disease severity. The concomittant presence of low concentrations of histidine, alanine and either glycine or pyrrolidone-5-carboxylic acid (PCA) in the SC was associated with FLG mutations with 92% specificity. Conclusions Our findings suggest a low prevalence of FLG mutations in mild AD and support an important role for filaggrin in determining the physicochemical parameters of the SC. The combined measurement of several filaggrin breakdown products in the SC may be useful to specifically predict the presence of FLG mutations.

Background/purpose: This research aims at assessing the influence of baseline skin colour on the ability of reflectance spectrophotometry to detect cutaneous erythema induced by a low concentration of methyl nicotinate (2.5 mM) (first objective), and to detect tanning induced by ultraviolet rays (UVA+UVB) at infra-erythemal doses (second objective). Methods: Two independent studies were conducted to reach their respective objectives, on 27 women for the first study and on 12 women for the second study. Skin colour measurements were expressed in two different ways: percentages of reflected light at increasing wavelengths λ (400 nm

To investigate the role of the angiogenic cytokine vascular endothelial growth factor (VEGF) during pregnancy and lactation, we used mice in which VEGF had been inactivated in mammary gland epithelial cells. Pups born to mutant mothers failed to thrive, displaying little milk in their stomachs. However, when they were transferred to control mothers they developed normally. Investigation of the mammary gland morphology revealed that lobulo-alveolar expansion into the fat pad was not complete in lactating mutant glands, and an accumulation of fat globules was evident in their secretory epithelium. In contrast to control glands, lactating mutant glands failed to up-regulate mRNAs for genes involved in milk secretion. Blood vessel density was comparable in pregnant mice of both groups but was only half that of controls in lactating mutant mice. FITC-labeled albumin injected intravenously (i.v.) into lactating mice extravasated rapidly and accumulated in the mammary gland epithelial cells in control animals, but was almost completely retained within the vessels in the mutants. Injection of recombinant VEGF i.v. reversed this effect. These findings demonstrate that mammary epithelium-derived VEGF is partially dispensable for angiogenesis during pregnancy and lactation, and by regulating vascular function during lactation, this factor is crucial to mammary gland differentiation and milk production.

Background/purpose: The variation of skin surface morphological indicators according to age has not been frequently studied. The aim of this work was to establish French Caucasian and Japanese reference ranges of these indicators according to age. Methods: Two studies were performed simultaneously in Paris and Sendai on 356 Caucasian and 120 Japanese healthy women aged from 20 to 80 years. Skin replicas were obtained from the volar forearm and analysed by interferometry. This analysis yielded 16 morphological indicators. Reference ranges according to age were established using the statistical methodology defined by Royston. Results/discussion: Reference ranges were found for 15 out of the 16 parameters for the French women as well as for the Japanese women. The models' truthfulness will have to be confirmed using new samples, larger if possible. Moreover, non-parametric methods will be used in order to compare the results provided by these approaches.

Zusammenfassung Hintergrund: Das Erysipel ist eine auf die Kutis und Subkutis beschrankte meist durch Streptokokken verursachte, schwere Weichteilinfektion, bei der eine antimikrobielle Therapie indiziert ist. In der Literatur sind viele verschiedene Therapieschemata beschrieben, die uberwiegend auf empirischen Daten basieren und nur teilweise durch Studien belegt sind. Material und Methoden: Ziel der vorgestellten Erhebung war es, mittels eines Fragebogens, die Erysipelbehandlung in Deutschland und Osterreich abzubilden und hieraus Therapieempfehlungen abzuleiten. Ergebnisse und Schlusfolgerung: In den befragten Kliniken wird das Erysipel praferentiell intravenos unter stationaren Bedingungen behandelt. Am haufigsten wird in der „first line”-Therapie Penicillin G (80 %) eingesetzt. Daneben werden Aminopenicilline (11 %), Cephalosporine (16,5 %) und Isoxazolylpenicilline (6,9 %) eingesetzt. Als „second line”-Therapie werden hauptsachlich Makrolide (63,5 %), Clindamycin (52,5 %), Penicilline (18,5 %), Cephalosporine (40 %) und Gyrasehemmer (20,5 %) sowie seltener Carbapeneme, Tetrazykline, Nitroimidazole, Glykopeptitantibiotika, Aminoglykoside, Cotrimoxazol, Fusidinsaure und Fosfomycin angewendet. Die Therapiedauer betragt im Durchschnitt 10 Tage. Als adjuvante Masnahmen kommen eine Antikoagulation, nichtsteroidale Antiphlogistika, Lokaltherapien, Ruhigstellung und eine Sanierung der Eintrittspforte zum Einsatz.

A recent study in our laboratories on the growth of keratinocytes at the culture medium/air interface has led to the identification of a novel thin sheet-like matrix that supports adherent cells. This novel matrix consists of components secreted by keratinocytes, including type IV collagen, and laminins 1 and 5, that self-assembled to a membrane structure. In the present study, a detailed ultrastructural characterization of this membrane was done with high-resolution electron microscopy after negative staining. The basic organization of the membrane was found to be a dense network of 8- to 10-nm-wide irregular rod-like elements. High-resolution examination and immunolabeling showed that type IV collagen filaments form the core of these elements, and other components including heparan sulfate proteoglycan in the form of 4.5- to 5-nm-wide ribbon-like "double tracks" are aggregated around it. These detailed features of the membrane strikingly resembled those of the basement membrane in vivo. These ultrastructural similarities indicate that the membrane may also have basement membrane-like functional properties, and suggest that it should be considered for testing in future medical applications.

Introduction Dehydration of the stratum corneum leads to sensations and symptoms of ‘dry skin’ such as skin tightness and itchiness. As these complaints are frequently experienced by airline travellers, the aim of this study was to investigate the changes in skin surface hydration during long distance flights. Methods The study was performed on four healthy Caucasian, and on four Japanese women aged 29–39 years, travelling on long distance flights. They had stopped using skin care products at least 12 h before, and did not apply them during the flights. The air temperature and relative humidity inside the cabin, as well as skin capacitance of the face and forearm of participants, were registered at several time points before and during the flights. Results Relative humidity of the aircraft cabin dropped to levels below 10% within 2 h after take-off and stayed at this value throughout the flight. Skin capacitance decreased rapidly on both the face and forearms with most pronounced changes on the cheeks where it decreased by up to 37%. Conclusion Our results demonstrate that during long distance flights, the aircraft cabin environment leads to a rapid decrease in stratum corneum hydration, an alteration, which probably accounts for the discomfort experienced by long distance aircraft travellers.

Inflammatory cytokines (IC) activate endothelial cell adhesiveness for monocytes and inhibit endothelial cell growth. Here we report the identification of the human guanylate binding protein-1 (GBP-1) as the key and specific mediator of the anti-proliferative effect of IC on endothelial cells. GBP-1 expression was induced by IC, downregulated by angiogenic growth factors, and inversely related to cell proliferation both in vitro in microvascular and macrovascular endothelial cells and in vivo in vessel endothelial cells of Kaposi’s sarcoma. Experimental modulation of GBP-1 expression demonstrated that GBP-1 mediates selectively the anti-proliferative effect of IC, without affecting endothelial cell adhesiveness for monocytes. GBP-1 anti-proliferative activity did not affect ERK-1/2 activation, occurred in the absence of apoptosis, was found to be independent of the GTPase activity and isoprenylation of the molecule, but was specifically mediated by the C-terminal helical domain of the protein. These results define GBP-1 as an important tool for dissection of the complex activity of IC on endothelial cells, and detection and specific modulation of the IC-activated non-proliferating phenotype of endothelial cells in vascular diseases.

Background/aims: The aim of this study was to compare the biophysical properties of different facial zones. Methods: We investigated transepidermal water loss (TEWL), skin temperature and sebum casual level (CL) on 90 adjacent test sites distributed on the forehead, cheeks and chin of five women. Results: All three parameters showed a symmetrical distribution around the facial median line. Only minor variations of individual values were found within the forehead and the chin areas. In contrast, the cheeks exhibited a distinct gradient with highest values in the paranasal zones and lowest on the cheek bones for all of the three parameters. The mean values on both cheeks of a given individual were nearly identical, and the patterns within the two cheeks were superimposable. Both CL and skin temperature distributions pointed out a “T-zone” with highest values on the forehead, on the chin and on the median part of the cheek. Conclusions: Our data demonstrate that biophysical skin properties differ considerably between different facial areas but that they follow a characteristic distribution.

Vascular endothelial growth factor (VEGF) is a central regulator of neoangiogenesis in inflammatory and neoplastic conditions. Ultraviolet irradiation is one of the mainstays of dermatological therapy for various inflammatory skin diseases. In the present study we have compared the effects of UV irradiation on the production of VEGF by keratinocytes (KC) and by the KC-derived cell lines A431 and HaCaT. Irradiation of A431 and HaCaT cells with both UVA (10 J/cm2 and 20 J/cm2) and UVB (8 mJ/cm2 and 16 mJ/cm2) led to strong upregulation of VEGF mRNA and protein. Induction of VEGF by UVA and UVB in these cells was mediated by different pathways, i.e. the generation of free radicals and the secretion of (a) soluble factor(s), respectively. Unlike KC-derived cell lines, no increase in VEGF production was observed in KC in primary culture after irradiation with the same UV doses. Increasing the irradiation dose in these cells of UVA to 40 J/cm2 led to a marked decrease in soluble VEGF, whereas doses as high as 32 mJ/cm2 UVB only minimally affected VEGF levels. Reduction of VEGF production by KC might contribute to the effect of UVA irradiation in inflammatory skin diseases. The differential response of primary KC and autonomously growing KC-derived cell lines to the induction of VEGF by UV light could favor neoangiogenesis in the vicinity of epidermal tumor cells in vivo, thereby endowing them with a growth advantage over normal cells.

A subset of patients with systemic mastocytosis (SM) develop acute myeloid leukaemia (AML). However, little is known about the biology of such leukaemias and their relationship to the mast cell (MC) lineage. We report on two female patients who suffered from SM and AML. According to FAB criteria, the leukaemias were classified as AML-M4 (patient 1) and AML-M0 (patient 2). The coexistence of the two distinct neoplasms (AML and SM) was demonstrable by immunostaining of serial bone marrow (BM) sections with monoclonal antibodies (mAb). In particular, the MC infiltrates were found to react with mAb against MC-tryptase and MC growth factor receptor c-kit (CD117), but not with mAb to CD15 or CD34. In contrast, the AML blasts were immunoreactive for CD15 (patient 1) or CD34 (patient 2), but did not express tryptase. The c-kit point mutation Asp Val at codon 816, considered to play a role in the transformation of MC progenitors, was detected in patient 1 in a BM cell fraction containing 4% MC. However, no c-kit mutation was found in pure AML blasts (

The bcl-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide variety of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nervus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cell carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.

Phototype classifications were initially developed in an attempt to predict the skin reactions of patients to phototherapy and are now widely used to advise individuals with regard to sun protection. A transversal study was conducted on the SU.VI.MAX cohort to estimate the frequency of sun-reactive skin features in a large, general adult population-based sample, and to describe the associations between these features. The data were collected 3 years after the beginning of the SU.VI.MAX nutritional intervention study on 4912 volunteers (2868 women aged 35-60 years and 2044 men aged 45-60 years). A multiple correspondence analysis was performed to study the associations between the features. The results showed that these features correspond to a one-dimensional phenomenon, which allowed us to establish a score to summarize skin sensitivity to sun exposure. Furthermore, we found a link between gender and phototype using the Cesarini classification (phototype > or = IV: 37% of women, 47% of men). The analysis of the relationship with sun-reactive skin features and the score revealed the same trend. Phenotypic evaluation appears to be a good estimator of skin sensitivity to sun exposure for clinical screening or for use in research, and is easy to collect at a lower cost. Moreover, the sun sensitivity difference between gender should be considered in education about photoprotection.