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Biomedical subjects

M Fartasch

Publications and source records attributed to M Fartasch.

At least 55 records · Page 3Linked to original sources
PubMed1996

Epidermal abnormalities may distinguish type 2 from type 1 and type 3 of Gaucher disease.

A major clinical challenge in Gaucher disease is the early and presymptomatic discrimination of type 2 (acute neuronopathic) from milder type 1 and type 3 Gaucher patients to enable appropriate management and counseling. Although most patients with Gaucher disease do not have skin abnormalities, a subset of patients with severe type 2 Gaucher disease display ichthyosiform skin. Analogous findings occur in the skin of type 2 (null allele) Gaucher mice. Ultrastructural and functional studies of epidermis from these mice reveal that glucocerebrosidase is required to generate functionally competent membranes for normal epidermal barrier function. We have extended our studies by examining the epidermal lipid content and ultrastructure in all three types of Gaucher patients. Only the type 2 Gaucher patients, some of whom had clinical ichthyosis, demonstrated an increased ratio of epidermal glucosylceramide to ceramide as well as extensive ultrastructural abnormalities, including the persistence of incompletely processed lamellar body-derived contents throughout the stratum corneum interstices. These epidermal alterations may provide a means for early differentiation of type 2 Gaucher disease.

Animals↗
PubMed1995

Expression of integrin receptors and ICAM-1 on keratinocytes in vivo and in an in vitro reconstructed epidermis: effect of sodium dodecyl sulphate.

Several integrin heterodimers such as alpha 2 beta 1, alpha 6 beta 4 and alpha v beta 5 are expressed on basal keratinocytes of the epidermis. Because overexpression of these integrins as well as induction of the intercellular adhesion molecule-1 (ICAM-1) have been found in inflammatory dermatoses, we sought to determine whether these modulations could be used as markers of skin irritation. In normal epidermis, topical application of 1% sodium dodecyl sulphate (SDS) for 24 h caused an upregulation of alpha 3, beta 1, alpha 6, beta 4, alpha v, beta 5 and to a lesser extent alpha 2 integrin chains as well as an induction of ICAM-1. To investigate whether these parameters could also be used for evaluation of skin irritancy in vitro, SDS was applied for 24 h to reconstructed epidermis on de-epidermized dermis (RE-DED). In RE-DED, integrin overexpression and aberrant alpha 5 expression was seen under normal in vitro culture conditions and topical application of SDS caused only marginal additional upregulation. We could not detect any ICAM-1 reactivity on either normal or irritated RE-DED. Our results demonstrate that the modulation of integrin and ICAM-1 expression can be used as markers of irritation of the epidermis in vivo, but not in vitro.

Biomarkers↗
PubMed1995

[Possibilities and limits of paraffin-embedded cell markers in diagnosis of primary cutaneous histiocytosis].

To date, the rare primary histiocytoses of the skin are diagnosed definitively on the basis of the clinical symptoms, H&E-stained sections, and demonstration of CD1 positivity in frozen sections and of Birbeck granules on electron microscopy. The improvement and analysis of antibodies with the ability to react in paraffin tissue allow retrospective evaluation and classification of these disorders. The antibodies for S-100-protein, peanut agglutinin (PNA) and PCNA (proliferating cell nuclear antigen) have been advocated for differentiation of the specific cells of Langerhans cell histiocytosis (LCH) from other histiocytic cell systems. To date the non-Langerhans cell histiocytoses (non-LCH) have no common ultrastructural and immunohistochemical characteristics. The infiltrate is made up of multiple cell populations, which are of significance for the cellular pathobiology (subtypes of monocytes/macrophages and dendritic cells). The number and distribution of the different monocyte/macrophages and dendritic cells and their ability to react with immunohistochemical markers in paraffin tissue can be completely different in different clinical entities. The antibodies against factor XIIIa (shown on xanthoma disseminatum) and the monoclonal antibody Ki-M1P (shown on juvenile xanthogranuloma) seem to be valuable in discrimination between LCH and non-LCH. Both markers show a positive staining pattern with the characteristic large macrophages. In juvenile xanthogranuloma, the foam cells and giant cells express Ki-M1P, KP1 and anti-cathepsin B. Other monocyte/macrophage markers with the ability to react in paraffin tissue, such as Mac387, lysozyme, alpha 1-antitrypsin and Leu-M1 (Anti-CD 15), in contrast, did not show a typical staining pattern with the characteristic large macrophages dominating the histological picture.

Biomarkers, Tumor↗
PubMed1995

Apolipoprotein E deficiency leads to cutaneous foam cell formation in mice.

Apolipoprotein E deficiency leads to familial dysbetalipoproteinemia characterized by increases in serum lipid levels, atherosclerosis, and cutaneous xanthoma. Apolipoprotein E is synthesized in many tissues in the body, including the epidermis. In the present study, we determined whether transgenic mice deficient in apolipoprotein E develop cutaneous xanthoma and the effect of dietary fat intake on these lesions. We also determined whether apolipoprotein E-deficient mice have abnormalities in cutaneous barrier function or stratum corneum structure. Homozygous apolipoprotein E-deficient mice (-/-) fed a high-fat diet displayed a diffuse inflammatory infiltrate in the dermis surrounding fat droplets in macrophages. In homozygous mice (-/-) fed a low-fat diet, similar lesions were seen but they tended to be focal and less prominent. In heterozygous mice (+/-) fed the high-fat diet, a few inflammatory cells were present in the dermis but foam cells were not seen. Control mice (+/+) fed a high-fat diet displayed scattered inflammatory cells in the dermis. Heterozygous mice (+/-) fed a low-fat diet were similar to control mice (+/+) fed a low-fat diet. The extent of foam cell formation correlated directly with the degree of atherosclerosis. There were no abnormalities in permeability-barrier function or stratum corneum structure in apolipoprotein E-deficient mice. Thus, the lack of apolipoprotein E production in the epidermis does not appear to lead to any detectable abnormality in structure or function of the stratum corneum. However, lack of apolipoprotein E leads to cutaneous foam cell formation, presumably secondary to disturbances in lipoprotein metabolism.

Animals↗
PubMed1995

Occupational contact dermatitis in bakers, confectioners and cooks. A population-based study.

A population-based study was performed to investigate incidence rates of occupational skin disease (OSD) in bakers, confectioners and cooks, as well as the rôle of endogenous and exogenous risk factors. In North Bavaria, all closed cases of OSD were recorded systematically in a 3-year period and the total number of employees in the food industry was known over the same period of time. Incidence rates of OSD and relative risks of atopic skin diathesis (AD) and respiratory atopy (RA) were calculated. The overall incidence rate (I) of OSD (in 3 years per 10.000 employees) was 67 (95% CI 58;76) in these occupations. Bakers had a higher risk of OSD, with an incidence of 191 (95% CI 156;226) compared to confectioners with I = 84 (95% CI 55;113) and cooks I = 34 (95% CI 28;40). Incidence rates were sex- and age-related. Females developed OSD with an incidence rate of 74 (95% CI 64;84) compared to males with I = 58 (95% CI 48;70). OSD occurred mostly between the ages of 15 and 24 years. Irritant contact dermatitis (ICD) was the main type of OSD. 36% of the bakers had an occupationally relevant Type I allergy, while Type I allergies were less frequent in confectioners (16%) and cooks (9%). Assuming a prevalence of 10% of AD in the general population the relative risk (RR) of developing OSD in bakers, confectioners and cooks with AD was 9.7, 10.5 and 5.2, respectively. There were only small differences in calculating sex-related RR of AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Anticardiolipin syndrome with only skin involvement].

In anticardiolipin syndrome (ACS) a typical antibody constellation is associated with thrombotic and hematologic disorders. Furthermore, recurrent abortion, cerebral ischemia and different skin disorders occur. We report the case of a 29-year-old female suffering for the first time from painful, necrotic deep ulcers on the upper and lower legs and livedo racemosa on the arms as a rare example of a merely cutaneous manifestation of ACS with no demonstrable underlying disease. After systemic treatment with high-dose methylprednisolone, azathioprin and hydrocolloid dressings, healing of the scar tissue occurred. Simultaneously, a maintenance dose of acetylsalicylic acid (100 mg/day) was administered. So far, neither cutaneous relapse nor other signs of ACS have occurred.

Adult↗
PubMed1994

Improved barrier structure formation in air-exposed human keratinocyte culture systems.

The epidermis (including stratum corneum) of human keratinocytes cultured at the air-liquid interface attached to an appropriate substrate shows a morphology closely mimicking that of its in vivo counterpart. In spite of the histologic similarities, the barrier function seems to be impaired. The aim of the present study was to characterize development and structure of the epidermal permeability barrier in two human skin recombinants using electron microscopy (including ruthenium tetroxide-post fixation technique) and analysis of lipid composition. The epidermis was reconstructed by growing human keratinocytes either on de-epidermized dermis or on a bovine collagen-containing matrix with active fibroblasts (Living Skin Equivalent). Ultrastructurally both culture systems showed a) an abnormal lamellar body delivery system, b) disturbance of transformation into lamellar lipid bilayers, c) an impaired structural organization and distribution of the epidermal lipids in the intercellular spaces. In either of the systems used, prolongation of the culture period did not induce any significant improvement in the stratum corneum lipid organization. Whereas the Living Skin Equivalent showed only sparse lamellar bodies, the number of lamellar bodies in the human keratinocyte culture on de-epidermized dermis grown in regular medium seemed to be comparable to native skin. Contrary to the Living Skin Equivalent, the keratinocyte culture on de-epidermized dermis contained a higher number of intracorneocytic lipid droplets correlating with a higher triglyceride content in the lipid analyses. By reconstructing the keratinocyte culture on de-epidermized dermis with the same medium as used for the Living Skin Equivalent, both lipid composition (lower triglyceride, higher ceramide contents) and structural organization were improved, and regular lamellar lipid bilayers comparable to those of native skin appeared.

Adult↗
PubMed1994

The irritant effect of different metalworking fluids.

The irritant effect of different water-based cutting fluids (CFs) on the skin was investigated in healthy subjects (n = 10) using 2 non-invasive bioengineering methods. Transepidermal water loss (TEWL) was measured by an evaporimeter EP1 (Servo Med), skin blood flow (SBF) was recorded with a laser Doppler flowmeter (MBF 3D, Moor Instruments England). Additionally all test sites were evaluated by visual scoring before measurement. 3 cutting fluids A, B and C from different manufacturers were tested at use concentrations of 4% or 5%. Single 24-h patch tests and repeated patch tests were performed on the volar side of the right forearm. Measurements were carried out before and after exposure to assess basal values and the skin response to CF. Tests with CFs A and C resulted in significant increase in TEWL after 24 h and after cumulative treatment, compared with controls (p < 0.01). The TEWL values for CF B did not differ from the water probe. An increase in SBF was found only for CFs A and C after cumulative patch testing (p < 0.01). In spite of their similar alkalinity, the 3 CFs showed different irritant skin reactions, due to their chemical components. This was verified particularly by measurement of TEWL.

Adult↗
PubMed1994

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier. A subset of type 2 Gaucher patients displays ichthyosiform skin abnormalities, as do transgenic Gaucher mice homozygous for a null allele. To investigate the relationship between glucocerebrosidase deficiency and epidermal permeability barrier function, we compared the stratum corneum (SC) ultrastructure, lipid content, and barrier function of Gaucher mice to carrier and normal mice, and to hairless mice treated topically with bromoconduritol B epoxide (BrCBE), an irreversible inhibitor of glucocerebrosidase. Both Gaucher mice and BrCBE-treated mice revealed abnormal, incompletely processed, lamellar body-derived sheets throughout the SC interstices, while transgenic carrier mice displayed normal bilayers. The SC of a severely affected type 2 Gaucher's disease infant revealed similarly abnormal ultrastructure. Furthermore, the Gaucher mice demonstrated markedly elevated transepidermal water loss (4.2 +/- 0.6 vs < 0.10 g/m2 per h). The electron-dense tracer, colloidal lanthanum, percolated between the incompletely processed lamellar body-derived sheets in the SC interstices of Gaucher mice only, demonstrating altered permeability barrier function. Gaucher and BrCBE-treated mice showed < 1% and < 5% of normal epidermal glucocerebrosidase activity, respectively, and the epidermis/SC of Gaucher mice demonstrated elevated glucosylceramide (5- to 10-fold), with diminished ceramide content. Thus, the skin changes observed in Gaucher mice and infants may result from the formation of incompetent intercellular lamellar bilayers due to a decreased hydrolysis of glucosylceramide to ceramide. Glucocerebrosidase therefore appears necessary for the generation of membranes of sufficient functional competence for epidermal barrier function.

Animals↗
PubMed1993

Structural relationship between epidermal lipid lamellae, lamellar bodies and desmosomes in human epidermis: an ultrastructural study.

The water permeability of the stratum corneum (SC) appears to be regulated primarily by the lamellar arrangement of lipid bilayers between the corneocytes. A significant body of evidence already exists, suggesting that the specific structural organization of these intercellular lipid lamellae is responsible for the very low water permeability of the intact skin and that these lipid-rich structures may also influence the process of desquamation in the SC. In this electron microscopic study the structure of the intercellular domains at different levels within the SC of normal skin from 18 healthy subjects has been evaluated with a special fixation protocol utilizing acrolein vapour as primary fixation, followed by a modified ruthenium tetroxide (RuO4)-post-fixation technique. This procedure permitted an insight into the process of post-secretory extracellular processing of the lamellar body (LB)-derived lipids into lamellar lipid bilayers. This transformation takes place in unique saccular invaginations of the intercellular domains, which indent the underlying stratum granulosum (SG) cells. In this specialized environment LB lipids are first processed into broad sheets before they become part of the typical lamellar lipid structure of the SC. Furthermore, in the process of lipid maturation distinct differences between inner and outer parts of the SC emerge, in particular an increase in both the number of the lamellae per intercellular space, and their order of arrangement. Moreover, distinct structural relationships between desmosomes (at the SG/SC interface and lower SC) and desmosomal remnants (at the stratum disjunctum) on the one hand, and lipid layers on the other, have been demonstrated, pointing to an important functional interaction of these components in normal human skin.

Adult↗
PubMed1993

Mal de Meleda keratoderma with pseudoainhum.

Pseudoainhum is an infrequent complication in the autosomal-recessive keratodermas. We describe two related families in which the diagnosis of mal de Meleda keratoderma has been confirmed by mode of inheritance and ultrastructural findings. One family member, a 9-year-old girl, developed pseudoainhum which threatened the viability of her little fingers. This responded to treatment with etretinate. The treatment dilemma posed by keratoderma-induced pseudoainhum in children, i.e. the concern over the possible skeletal toxic effects of long-term etretinate treatment vs. the risks and outcome of surgery, is discussed.

Ainhum↗
PubMed1993

Progressive partially symmetric erythrokeratodermia with deafness: histological and ultrastructural evidence for a subtype distinct from Schnyder's syndrome.

An atypical case of the rare genodermatosis erythrokeratodermia progressiva partim symmetrica (EPPS) with deafness and myopathy is described. Our findings suggest that this case of EPPS with deafness and myopathy represents a distinct entity of atypical erythrokeratodermias with characteristic epidermal and dermal skin changes.

Adult↗
PubMed1992

Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics.

A characteristic feature of non-eczematous atopic dry skin (DS) appears to be an impaired water permeability barrier (WPB) function. The WPB is constituted by intercellular lipid lamellae, located between the horny cells of the stratum corneum (SC), which are provided by exocytosis of lamellar bodies (LB). The aim of this study was to elucidate whether alterations in the dynamics of LB-extrusion could be responsible for this WPB disturbance. In an ultrastructural morphometric comparison the relative volume of LB in the two uppermost subcorneal layers in DS of atopics (n = 9) and healthy skin of controls (n = 7) was determined. The LBs were differentiated into extracytoplasmic LB, i.e. with the cell membrane already fused, and intracytoplasmic LB, i.e. entirely located within the cell. The total volume in the two cell layers of the stratum granulosum did not differ between atopics and controls. However, separate evaluation of the two LB-compartments revealed statistically significant differences between atopics and healthy controls. In the second uppermost cell layer of the stratum granulosum only 13% of the total LB volume of this layer had already fused with the cell membrane in the atopics as opposed to 42% in the controls. On the other hand more LB remained undelivered within the cells of the uppermost SG cell layer of the atopics (26% in atopics versus 8% in controls, P < 0.01). These findings suggest that a pathological extruding mechanism of LB in DS may be at least partly responsible for the recently detected biochemical alterations of epidermal lipids, and for the deficient WPB.

Adult↗
PubMed1992

Chronic actinic dermatitis with vitiligo-like depigmentation.

This report describes two patients suffering from severe chronic actinic dermatitis. Unusual widespread vitiligo-like depigmentation occurred during the course of the disease. The progression of these lesions was triggered by the chronic actinic dermatitis. Loss of pigment and complete absence of tyrosinase positive melanocytes were found in depigmented skin of both cases. Immunohistological investigation of the inflammatory infiltrate in case 2 revealed a predominance of CD-8 positive cytotoxic/-suppressor lymphocytes. Analysing the adjacent pigmented epidermis of progressive depigmenting lesions a dense exocytosis of CD-8 T-cells was notable. This distribution suggests cytotoxic destruction of melanocytes as the cause for the vitiligo-like depigmentation.

Aged↗