Leena Bruckner-Tuderman

Type VII collagen is expressed but anchoring fibrils are defective in dystrophic epidermolysis bullosa inversa

A patient with dystrophic epidermolysis bullosa inversa was studied using electron microscopy and indirect immunofluorescence using antibodies to matrix macromolecules of the dermo‐epidermal junction zone. There was splitting below the lamina densa with an apparently normal basement membrane, but a lack of intact anchoring fibrils and with a disarranged papillary connective tissue. Indirect immunofluorescence examination with antibodies to type VII collagen, the major structural protein of anchoring fibrils, showed a normal linear staining pattern. Synthesis of type VII collagen which is unable to form stable, resistant anchoring fibrils may be a distinct feature of this subtype of recessive dystrophic epidermolysis bullosa.

Nail changes in epidermolysis bullosa : clinical and pathogenetic considerations

Nail changes in epidermolysis bullosa (EB) are common, but although they are highly suggestive of the disease, they are not pathognomonic. They are the result of abnormalities of the nail matrix and nail bed, associated with the pathogenetic alterations of the dermo‐epidermal junction which occur in EB. In addition, secondary trauma in the areas of epidermal‐dermal separation, and chronic inflammation of the nail matrix, are probable contributory factors, even in non‐scarring forms of EB.

Epidermolysis bullosa junctionalis progressiva in three siblings

Three siblings of Swiss origin with epidermolysis bullosa junctionalis progressiva are described. The following clinical features were present from school age; dystrophy of the nails, non‐scarring blistering of the skin, mild skin atrophy, hypodontia and dental caries. Light microscopy showed subepidermal blistering. Direct immunofluorescence was negative. On indirect immunofluorescence staining of a fresh spontaneous blister, bullous pemphigoid antigen and laminin were localized to the blister roof, and collagen IV and collagen VII to the blister base, indicating junctional splitting. Electron microscopy revealed a normal dermo‐epidermal junction zone, including normal hemidesmosomes. There were no deposits of electron‐dense amorphous material.

Type VII collagen is a component of cylindroma basement membrane zone

Cylindroma basement membranes (BMs) were studied by electron microscopy and immunofluorescence with antibodies to Types IV and VII collagen in order to correlate the ultrastructure with the biochemical characteristics. Type IV collagen served as a marker for lamina densa structures and Type VII collagen for the anchoring fibrils. Ultrastructurally, the cylindroma BMs were composed of a wide band of BM‐like material in which numerous anchoring fibrils were embedded. The BMs surrounding the tumor cell clusters and nodules of BM‐like material entrapped within the tumor cell islands stained positively for both Types IV and VII collagen. We conclude, that anchoring fibrils are a major component of cylindroma BM zone. A trichoepithelioma investigated as control showed a BM similar to the one found at the dermoepidermal junction, i.e. a BM distinctly different from the one of cylindroma. The trichoepithelioma BMs and nodules of BM‐like material included within the tumor also stained positively for both Type IV and VII collagen.

Expression of type VII collagen, the major anchoring fibril component, in normal and neoplastic human nervous system.

The distribution of type VII collagen was examined in the normal human nervous system, in brain tumour biopsies and in glioma cell lines by immunohistochemistry and western blotting. In normal tissue, positivity was observed beneath choroid plexus epithelial cells and around pineal gland and pituitary gland cell nests, while other brain regions and peripheral nerves were negative. Expression was preserved in most related tumours (choroid plexus papilloma, pineoblastoma, pituitary adenoma). Scattered abnormal vessels showed neoexpression of type VII collagen in about half of the astrocytic and ependymal tumours. Glioma cells in situ were consistently negative for type VII collagen, where-as the glioblastoma cell lines were positive. Our results suggest that anchoring fibrils or at least epitopes of their major structural component are present in normal and pathological cerebral structures, indicating a unique distribution of type VII collagen in the nervous system.

Pathogenesis of mechanobullous disorders

Abstract Recent advances in the molecular biology of the dermo‐epidermal basement membrane zone have contributed greatly to our understanding of the etiopathogenetic pathways underlying mechanobullous disorders. Genetic linkage was established between the keratin gene clusters and epidermolysis bullosa simplex, and keratin mutations were identified in several patients. Anchoring filaments and the α6β4 integrin are likely to be affected in junctional EB. Genetic linkage was established between the collagen VII gene and both dominant and recessive subtypes of dystrophic epidermolysis bullosa. and different molecular abnormalities of collagen VII leading to formation of non‐functional, rudimentary anchoring fibrils were observed in several families. These discoveries that led to definition of mutations underlying EB also help us to understand the normal physiology and function of the affected structures. They may also point the way to new therapeutic strategies for common acquired blistering diseases and disturbances of epithelialization in general.

Patch Test Results of the Dermatology Clinic Zurich in 1989: Personal Computer-Aided Statistical Evaluation

The patch test results of 921 consecutively tested patients were registered on an IBM personal computer. A computer program based on the dBase III plus database software, especially designed for this purpose, was used. The statistical evaluation was performed with dBase III plus. 59% of the probands were females and 41% males. The average age was 42.8 years. 26% of the probands were inpatients and 74% outpatients. A majority of the patients presented with eczema of the hands, face or the lower legs. The largest occupational groups were houseworkers and cleaning personnel, office workers and pensioners. To 450 of the 921 patients, at least 4 test series were applied simultaneously. These included European standard, vehicles and emulgators, topical medications, and preservatives and biocides. The other 20 test series available were employed only by 2-81 patients each. The highest sensitization rates were found with: nickel, 18.7%; cobalt, 10.2%; balsam of Peru, 8.8%; framycetin, 8.0%; neomycin, 6.8%; potassium dichromate, 6.1%; p-phenylene diamine, 5.4%; paramix, 4.9%; formaldehyde, 4.8%, and (chlor)methylisothiazolinone, 4.7%. The critical evaluation of the data showed two kinds of problems: first, test-specific aspects led to optimization of the patch test procedures; second, the crucial importance of an adequate statistical analysis for epidemiological investigation was revealed.

Epidermolysis Bullosa Dystrophica Inversa in a Child

Abstract: A 4‐year‐old child with dystrophic epidermolysis bullosa inverse is described. Clinical features were blistering of the skin, erosions, scarring and milia formation. The areas involved included the trunk, with preference for the axillary and inguinal folds, the neck and sacral area, and proximal extremities. Notably, the hands and feet were completely spared, with only mild nail dystrophy. Ultrastructural analysis revealed dermolytic blistering and absent or rudimentary anchoring fibrils. Collagen VII, the main structural protein of these fibrils, was present in the skin, as shown by indirect immunofluorescence. These findings suggest that a mutation that prevents appropriate supramolecular aggregation of collagen VII into anchoring fibrils may underlie this subtype of dystrophic epidermolysis bullosa in some patients.

Erbkrankheiten: gestern, heute und morgen

Vor 90 Jahren hat Gregor Mendel in Brunn die sog. Mendel’schen Gesetze entdeckt. Seither hat im Bereich der Erbkrankheiten eine sturmische Entwicklung eingesetzt, die nicht zuletzt dank molekularbiologischen Methoden in den nachsten Jahren zu einem neuen Erkenntnisschub fuhren wird.