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T L Diepgen

Publications and source records attributed to T L Diepgen.

At least 19 recordsLinked to original sources

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

Recent epidemiological and genetic studies in atopic dermatitis.

In a prospective computerized study, basic and minor features of atopic dermatitis were studied systematically in established cases of atopic dermatitis (AD; n = 428) and compared with subjects randomly collected from the caucasian normal population of young adults (NP; n = 659). Complete genetic data (history of AD, allergic rhinitis, allergic asthma) were obtained from the first-degree relatives of all subjects (about 9,000 family members). In young adults, atopy was found in 22.5% (AD 4.7%, allergic rhinitis 17.9%, allergic asthma 4.8%). Of 428 AD patients, 54% had 'pure' AD and 46% suffered from a 'mixed' type with concomitant respiratory allergies (RA). The general risk of developing AD and atopy increases with each first-degree family member already suffering from atopy. Our study further supports the evidence of a genetic influence on symptom specificity. Risk figures for genetic counselling are given. The complex interplay of atopic symptoms and signs in the diagnosis of AD has been analysed by a CART analysis. Compared with non-eczematous controls, the odds ratios (OR) of frequent features in AD are as follows: xerosis (OR 27.9, 95%-CI 23.2-33.8), itch when sweating (OR 25.4, 95%-CI 21. 1-30.1), white dermographism (OR 19.3, 95%-CI 16.2-23.2), wool intolerance (OR 15.8, 95%-CI 13.40-18.5), whereas the OR of elevated IgE (> 150 U/ml) was only 5.0 (95%-CI 4.3-5.8). But when comparing the AD patients with concomitant RA separately, the odds ratio is increased to 16.2.

Adult

The barrier function in atopic dry skin. Disturbance of membrane-coating granule exocytosis and formation of epidermal lipids?

Non-eczematous atopic dry skin (DS) shows an enhanced transepidermal water loss denoting an impaired water permeability barrier (WPB) function. The WPB is formed by intercellular lipid lamellae located between the horny cells of stratum corneum (SC). The lipids are provided via the exocytosis of membrane-coating granules (MCG). By differentiating two dynamic states of MCG, the ultrastructural morphometric comparison of atopic DS and healthy skin of controls revealed a retarded and incomplete extruding mechanism of these organelles. Additionally the structure and spacial organization of the epidermal lipids in DS and healthy skin were visualized and analysed by applying a special primary fixation (acrolein vapour) and post-fixation with ruthenium tetroxide. The present findings suggest that some pathologic extruding mechanism of MCG in DS may be responsible, at least partly, for the recently detected biochemical alterations of epidermal lipids and for the deficient WPB.

Adult

[A special form of Bazex acrokeratosis in small cell bronchial cancer].

A 66-year-old pensioner developed distinct, erythematosquamous and keratonic lesions on the hands and feet within 2 months, and also a progressive red-bluish discoloration of the whole integument. Clinical and X-ray exploration revealed a still asymptomatic small-cell bronchial carcinoma, so that the otherwise inexplicable skin lesions made an acrokeratotic paraneoplastic syndrome of the Bazex type seem most likely. This very rare syndrome has hitherto been observed only in patients with carcinomas of either the bronchial or the upper digestive tract, with or without cervical and mediastinal lymph node metastases. We report on our third patient with Bazex-type acrokeratosis, mainly because of the uncommon distribution and severity of his otherwise typical lesions. In addition, recent reports on this syndrome in the literature are reviewed.

Acrodermatitis

Phenotyping of immunocompetent cells in normal labial and palatal salivary glands and in non-autoimmune sialadenitis.

Different types of inflammatory cells in healthy major and minor salivary glands (SG), including those in labial and palatal non-autoimmune sialadenitis, were quantified immunohistochemically. Plasma cells, mainly IgA type predominated in all SG types, with the smallest number seen in the palatal glands. The numbers of common leukocyte antigen (CLA) reactive lymphocytes were greater in major SGs than in minor ones and were predominantly UCHL1 positive T cell type. Macrophages and neutrophils were absent in palatal glands, rarely present in labial ones and usually present in major SGs. Increases in the number of IgG and IgM plasma cells and lymphocytes (CLA+) which include both UCHL1+ T and L26+ B cell types, were found in non-autoimmune labial and palatal sialadenitis. There was no significant correlation between the number of the inflammatory cells and the degree of glandular atrophy in both labial and palatal non-autoimmune sialadenitis. Increase in their number represents a protective response of these glands in contrast to the inflammatory cells in major autoimmune sialadenitis playing there a pathogenetic role.

Antigens, Differentiation

Clinically relevant differences between amelanotic malignant melanoma and granuloma pyogenicum.

Macroscopic discrimination between amelanotic malignant melanoma (aMM) and the so-called granuloma pyogenicum (GP) is often uncertain since reliable criteria for a clear differentiation of either growth are lacking. In a search of such criteria we analysed the data of 57 consecutive in-patients with cutaneous aMM and of 83 with GP presenting at our Department during the years 1970-1988. The following items were compared with each other: duration from growth onset to definite diagnosis, site of growth, age and sex of the patients. Significant differences (p less than 0.01) between either growth were found for all items evaluated. Our results substantiate the hitherto gained impression of a remarkably shorter median history of GP as compared to aMM (5 vs. 26 weeks). Furthermore, aMM prevailed in elder (age greater than 50 years) particularly female (70%) patients, whereas GP developed about equally in both sexes and at all ages. Site distribution was also found to differ for either growth (GP predominantly in the head and neck region, rarely on lower limbs; aMM in all areas, rarely on the trunk). These data yield additional measures for clinical distinction between aMM and GP.

Adolescent

Detection of migration inhibitory factor (MIF) by a monoclonal antibody in the microvasculature of inflamed skin.

Macrophage migration inhibitory factor (MIF) is known as a mediator of cellular immunity with specific effects on the differentiation of mononuclear phagocytes. There is little information on the production of MIF in vivo and its role in the pathophysiology of inflammation. We studied the distribution of MIF in various tissues with a monoclonal antibody against human MIF (1C5/B) using the indirect immunoperoxidase method. Here, we investigate the expression of MIF on endothelial cells of dermal vessels. Our results show that dermal vessels may constitutively express MIF and can be strongly activated to express MIF in acute inflammations such as eczema and psoriasis in contrast to the chronically infiltrated skin from patients with pseudolymphomas and sarcoidosis. In these cases a possibly MIF defective state of vessels and a restriction of positive vessels to distinct anatomical sites of the inflamed skin was detected. The significance of the described association of MIF with vascular endothelium is still a matter of speculation. MIF expression on endothelium may provide an important differentiogenic signal for mononuclear phagocytes on their way to the tissue site.

Antibodies, Monoclonal

Immunohistochemical and ultrastructural study of histiocytosis X and non-X histiocytoses.

The diagnostic reliability of ultrastructural and immunohistochemical examinations on routinely processed biopsy specimens of cutaneous histiocytic proliferations (histiocytosis X, n = 7; juvenile xanthogranuloma, n = 4; necrobiotic xanthogranuloma, n = 2; traumatic granuloma of the tongue, n = 1) was evaluated. S-100 protein, peanut agglutinin, and the antibody Mac-387 were used as markers for histiocytes. The frequency of Birbeck granule-containing cells in seven histiocytosis X lesions did not correspond with the number of S-100+ or peanut agglutinin+ cells. All neoplastic histiocytosis X cells were positive for S-100 protein and peanut agglutinin but were negative for Mac-387. Histiocytes of juvenile xanthogranuloma, necrobiotic xanthogranuloma, and traumatic granuloma were strongly positive for Mac-387 but were negative for S-100 protein and peanut agglutinin, except for the peanut agglutinin-reactive Touton giant cells. Mac-387 reliably differentiates histiocytic proliferations of the monocyte/macrophage system from those of the dendritic cell system. For the diagnosis of histiocytosis X, both S-100 protein and peanut agglutinin positivity in histiocytes is as reliable as ultrastructural demonstration of Birbeck granules.

Adult

Abnormalities of keratinocyte maturation and differentiation in keratosis palmoplantaris striata. Immunohistochemical and ultrastructural study before and during etretinate therapy.

Keratoderma striatum (Brünauer-Fuhs type) with linear keratotic elevations on the palms and small islets (areata form) on the soles is a rare form of palmoplantar keratoderma (PPK). An immunohistochemical and ultrastructural study has been performed to characterize the altered keratinization and maturation patterns in this disease before and during complete clinical remission on therapy with etretinate. Anticytokeratin antibody KL1 showed no significant difference in reaction pattern either between healthy controls and PPK or following therapy. Earlier expression of both filaggrin and involucrin was found in PPK in comparison with the controls. During etretinate therapy the filaggrin pattern returned to normal, whereas the altered involucrin pattern was not influenced. Ultrastructural investigations before treatment revealed tightly packed tonofibrils (TF) and large masses of keratohyalin (KH) granules with abnormal configuration. During therapy the TF and KH granules were reduced in number and size. KH granules now showed frayed borders. Moreover, a transitional cell zone, focal parakeratosis with lipid droplets, and dyskeratotic cells became apparent. The normalization of filaggrin pattern accompanying the clinical remission of these lesions implies a role of this keratinocyte differentiation protein in the pathogenesis of these lesions. Since etretinate is assumed to act at a very late stage of epidermal differentiation, there was no influence on the altered expression of involucrin during etretinate therapy. Despite the clinical remission, fine structural abnormalities persisted, indicating that the deviations from the normal keratinocyte differentiation program in PKK occur very early.

Adult

Alteration of cell surface carbohydrates associated with ordered and disordered proliferation of oral epithelia: a lectin histochemical study in oral leukoplakias, papillomas and carcinomas.

Cell surface carbohydrates in healthy oral mucosa (n = 15), leukoplakias without (n = 48) and with (n = 62) dysplasia, oral papillomas (n = 6) and squamous cell carcinomas (SCCs) (n = 40) were examined using the lectins peanut agglutinin (PNA), Ulex europaeus agglutinin I (UEA I), soybean agglutinin (SBA), Helix pomatia agglutinin (HPA), and Griffonia simplicifolia agglutinin I (GS I-B4). Binding of these lectins in formalin-fixed, paraffin-embedded tissues was demonstrated using either the peroxidase-anti-peroxidase (PAP) method or the avidin-biotin method. Healthy oral epithelia revealed binding sites for these lectins mostly in the suprabasal keratinocytes with occasional PNA binding also in their basal cells. Unlike healthy mucosa, a number of leukoplakias without and with dysplasia revealed receptor sites for UEA I also in their basal layer. Only those keratinocytes undergoing squamoidal differentiation exhibited SBA binding. Staining patterns of UEA I and SBA did not vary significantly between either leukoplakias without and with dysplasia or papillomas and SCCs. Conversely, a reduction or lack of binding sites for PNA (Gal beta 1-3GalNAc), HPA (D-GalNAc alpha) and GS I-B4 (alpha D-Gal) was observed more frequently in leukoplakias with dysplasia and SCCs contrasting their counterparts lacking epithelial dysplasia. Cell surface glycosyl residues play an important role in the regulation of cell proliferation and epithelial growth. Aberrant glycosylation in oral dysplastic leukoplakias and carcinomas leading to the lack of the relevant terminal sugar residues from their cell surface carbohydrates is probably a major reason for the hyper-/disordered proliferation.

Carbohydrate Metabolism

[Grotton's acrogeria with bone involvement].

A 13-year-old girl had a bird-like face, deficiency of the subcutaneous fatty tissue, dry, thin, transparent and wrinkled skin, especially on the hands and feet, prominent veins and telangiectasia and mottled hyper-pigmentation. X-ray studies revealed acro-osteolysis of the hands and feet. The clinical features corresponded well with Gottron-type acrogeria. The clinical symptoms of premature ageing syndromes, such as progeria, lipodystrophia totalis, Cockayne syndrome, metageria and acrogeria are summarized briefly and compared with the clinical picture observed in our patient.

Adolescent

[Results of mechanical stresses from removable dentures on ridge mucosa and bone].

247 human cadaver jaws (obtained from 115 complete denture-wearers, 98 partial denture-wearers, 34 control persons) were examined histopathologically to determine if there is a correlation between tissue response and type of prosthetic management. The pathohistological changes of tissue and bone were evaluated statistically according to sex, age and topography of maxilla and mandible. The highest number of pathological findings was associated with those complete dentures and partial dentures where the biomechanical principles of construction had not been observed. Age, sex and topography, however, do not reveal any significant influence on tissue and bone.

Aged

[Textile intolerance in atopic eczema--a controlled clinical study].

In patients suffering from atopic dermatitis (AD), we often find intolerance reactions against wool, whereas irritation by synthetic fibers is still a matter of discussion. In a randomized clinical study on 55 patients with AD and 31 healthy controls, we investigated the irritative capacity of poncho-like shirts made of 4 different materials (A: cotton; B, C, D: synthetics of different fiber structure). The intensity of itching or discomfort due to repeated wearing of these shirts was evaluated by means of a point system (max.comfort = 10 points, max. discomfort = 1 point). Our study clearly showed that the irritative capacity of synthetic shirts is significantly higher in patients with AD, while cotton shirts were best tolerated. We also observed significant difference regarding the surface structure and diameter of the synthetic fibers under investigation.

Adult

[Characteristics of polymorphous light dermatosis--results of a prospective survey and study of 302 affected patients].

In a prospective study on 302 patients (females = 87%), we registered the historical and clinical data of polymorphous light eruption (PLE) and compared our results to similar studies from Finland, Sweden, and the USA. The mean age of onset of the disease was 24.0 years; the average duration time was 10.1 years. We found the following clinical and historical characteristics of PLE: skin types I and II - 49%; positive family history - 29%; latent period between sun exposure and the first skin eruptions - in 39% less than 2 hours, in 5% 3 days and more. Mostly we observed paular eruptions and strong pruritus, and usually the typical body areas were involved (i.e. décolleté, upper and lower arm, thigh, back of the hand, and face). In 64% of the patients who avoided exposure to the sun, the PLE did not continue but less than a week. Our findings may supply a useful tool regarding the diagnosis of ambiguous photodermatoses.

Adolescent

Atopic dermatitis--ichthyosis vulgaris--hyperlinear palms--an ultrastructural study.

Some 30-50% of cases of atopic dermatitis (AD) are believed to be associated with autosomal dominant ichthyosis vulgaris (ADI). The diagnosis of ADI can be proved by the ultrastructural demonstration of fewer and abnormal keratohyalin (KH) granules in all ADI patients, even in clinically unaffected skin. To prove the suggested frequent association of ADI with AD, an ultrastructural investigation of dry skin of 49 AD patients was performed. Only in 2 (4%) patients ADI could be confirmed by electron microscopy. In 17 patients, including the 2 patients with abnormal KH, hyperlinear palms were clinically seen. The present study yields evidence that hyperlinear palms, if present, and dry skin are in most cases a phenotypic marker of AD and not a sign of concomitant ADI. A histologically absent stratum granulosum in AD does not signify by itself a manifestation of concomitant ADI.

Adolescent

Are hyperlinear palms and dry skin signs of a concomitant autosomal ichthyosis vulgaris in atopic dermatitis?

In 30% to 40% of cases atopic dermatitis (AD) is believed to be associated with autosomal dominant ichthyosis vulgaris (ADI). The diagnosis of ADI can be proved by the ultrastructural demonstration of a defective keratohyalin (KH) synthesis, resulting in minute granules of crumbly appearance in only one layer of granular cells. To investigate the suggested frequent association of ADI with AD, ultrastructural examination of dry skin of 49 AD patients was performed. Only in 2 patients abnormal KH was demonstrated by electron microscopy. 17 patients, including the 2 patients with abnormal KH, showed hyperlinear palms. The present study shows that hyperlinear palms and dry skin are in most cases a phenotypic marker of AD alone and not a sign of concomitant ADI. A histologically one-layered or absent stratum granulosum may occur in the dry skin of patients with only AD and does not indicate a manifestation of concomitant ADI in all cases.

Adolescent

Evaluation and relevance of atopic basic and minor features in patients with atopic dermatitis and in the general population.

In a prospective computerized study on atopic dermatitis (AD) several basic and minor clinical features in patients with AD (n = 110) and a sample of the normal population (n = 527) was studied systematically and analysed statistically with regard to their diagnostic importance. On basis of chi-square values a diagnostic score system was constructed which might help to establish a firm diagnosis of AD in patients with ambiguous cutaneous inflammatory disease. Based on this score system patients with more than 10 points should be considered atopic, patients with 6 to 10 points are suspected to be atopics. An association between serum IgE and the amount of atopic points was found. Seven percent of the normal population sample proved to be obviously atopic, another 19% were suspected to be atopics.

Adult