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Biomedical subjects

L Bruckner-Tuderman

Publications and source records attributed to L Bruckner-Tuderman.

At least 109 records · Page 6Linked to original sources
PubMed1992

Anchoring fibrils, collagen VII, and neutral metalloproteases in recessive dystrophic epidermolysis bullosa inversa.

Structure of the anchoring fibrils, expression of collagen VII, and gelatinolytic activity in skin fibroblasts were assessed in six patients with epidermolysis bullosa dystrophica (EBD) inversa and in control groups consisting of probands with other EBD subtypes and healthy individuals. All six patients with EBD inversa, as well as the patients with generalized non-mutilating and localized EBD, showed positive staining with antibodies to collagen VII, the major anchoring fibril protein. Four patients with severe generalized mutilating EBD exhibited negative staining. Ultrastructurally, normal anchoring fibrils were demonstrable in uninvolved skin of patients with localized, inversa, and generalized non-mutilating subtypes. At the same time, a high degree of variability was observed in the amount and quality of anchoring fibrils in the various stages of lesional skin, including co-existence of normal and partially degraded anchoring fibrils. Of all 12 patients only one localized and two inversa cases showed an increased gelatinolytic activity in vitro. However, the high activity was associated with neither the severity of the disease nor the inversa subtype. In addition, intact collagen VII could be extracted from the dermis of one inversa patient. The present data show no correlation between increased in vitro gelatinolytic activity and abnormalities of the anchoring fibrils or collagen VII in skin of patients with recessive EBD, and therefore suggest molecular heterogeneity of the causative pathogenetic mechanisms.

Adolescent↗
PubMed1992

Pathogenesis of mechanobullous disorders.

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 alpha 6 beta 4 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.

Animals↗
PubMed1992

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.

Adolescent↗
PubMed1992

Sensitization to the isothiazolinone biocide. Report of the Swiss Contact Dermatitis Research Group 1988-1990.

The rate of sensitization to isothiazolinones (Kathon CG) detected in Switzerland rose from 3.5% (out of 2,491 patients) in 1987 to 6.3% (out of 982 patients) in 1988 and 5.6% (out of 2,295 patients) in 1989-90. This rate of sensitization appears to be related to the more and more widespread use of isothiazolinone biocide in cosmetics, domestic products and in industry.

Cosmetics↗
PubMed1992

Epidermolysis bullosa acquisita, a rare late complication of allogeneic bone marrow transplantation?

We report a rare disease of skin and oropharyngeal mucosa in a 28-year-old patient occurring 2 years after an allogeneic bone marrow transplantation. The dermatologic diagnosis was unambiguously epidermolysis bullosa acquisita according to the immunofluorescence and clinical presentation. Treatment with cyclosporin A and prednisone resulted in resolution. This autoimmune skin disease may be a manifestation of graft-versus-host disease, but the relationship must remain speculative.

Adult↗
PubMed1991

Increased gene expression of matrix metalloproteinase-3 (stromelysin) in skin fibroblasts from patients with severe recessive dystrophic epidermolysis bullosa.

Gene expression of matrix metalloproteinase 3 (MMP-3 = stromelysin) was examined in the skin fibroblasts obtained from patients with severe recessive dystrophic epidermolysis bullosa (RDEB). Steady-state mRNA level of MMP-3 was selectively increased in the unstimulated RDEB cells by a post-transcriptional mechanism. A parallel study on the susceptibility of type VII collagen to MMPs revealed that this type of collagen is degraded by MMP-3, but not by MMP-1 (collagenase). These data suggest that MMP-3 may play an important role in the blister formation fo the skin in RDEB patients by the degradation of anchoring fibrils consisting of type VII collagen.

Blotting, Northern↗
PubMed1991

Animal model for dermolytic mechanobullous disease: sheep with recessive dystrophic epidermolysis bullosa lack collagen VII.

A severe congenital mechanobullous disease with dermolytic blistering and recessive inheritance is described in sheep. The affected animals of wild and inbred flocks of the breed Weisses Alpenschaf (WAS) have blisters of skin, oral mucosa, tongue, and esophagus at birth or within the first week of life. Exungulation occurs early, and severe erosions in the mouth lead to difficulty in feeding. Electron microscopic examination revealed sub-lamina densa splitting in natural or fresh friction blisters and absence of identifiable anchoring fibrils in clinically uninvolved skin. Antigen mapping localized laminin and collagen IV to the blister roof. Indirect immunofluorescence staining with antibodies to collagen VII, the major structural component of the anchoring fibrils, demonstrated a complete absence of reaction in clinically uninvolved tissues of the affected sheep, whereas in normal sheep a strong linear fluorescence was seen at the epithelial-mesenchymal basement membrane zone. Dermal extracts of normal sheep contained intact collagen VII, but epidermal and dermal extracts from the affected sheep lacked this collagen or its fragments in immunoblotting experiments. Based on genetic, clinical, ultrastructural, and immunochemical findings, the sheep disorder corresponds to the severe mutilating subtype of recessive dystrophic epidermolysis bullosa in humans and can be used as an animal model to investigate the human disorder.

Animals↗
PubMed1991

Cylindroma overexpresses collagen VII, the major anchoring fibril protein.

The cell clusters of the human adnexal tumor, cylindroma, are surrounded by an unusual, thick, unorganized basement membrane-like zone in vivo. Ultrastructural analysis of this electron-dense zone revealed recesses that contained numerous anchoring fibrils. Indirect immunofluorescence staining with antibodies to collagen VII, the major structural component of the anchoring fibrils, showed strong fluorescence of this zone. Collagen VII could be isolated from tumor tissue by limited pepsin digestion or by extraction with chaotropic agents. Cylindroma cells were cultured from the tumor and passaged several times. The cells exhibited a strong expression of collagen VII in vitro, when assayed with immunofluorescence staining or immunoblotting of culture extracts. These results suggest that cylindroma can be used as an abundant source to produce collagen VII in vitro to study the biosynthesis and regulation of collagen VII and the formation of the anchoring fibrils, as other culture systems have failed to produce ample amounts of this anchoring fibril protein.

Aged↗
PubMed1991

Epithelial-mesenchymal interactions enhance expression of collagen VII in vitro.

Expression of collagen VII, the major structural protein of the anchoring fibrils, was assessed in vitro using indirect immunofluorescence staining and immunoblotting of collagen VII isolated from cultures. A very low level of expression was observed in monocultures of normal human fibroblasts or keratinocytes, but the expression was greatly stimulated when fibroblasts and keratinocytes were co-cultured. Primary skin explants under culture conditions supporting growth of both cell types, or mixed co-cultures of purified fibroblasts and keratinocytes, exhibited clearly enhanced synthesis of collagen VII, and the intact tissue form of this collagen could be extracted from small co-cultures. Three-dimensional skin equivalents were constructed with fibroblasts embedded in a contracted gel of collagen I and III, with an overlying stratified keratinocyte epithelium. In these equivalents, expression of collagen VII was observed primarily in the lowest epithelial cells, indicating that these cells are the main manufacturers of collagen VII. Laminin and collagen IV were deposited in a linear fashion onto the epithelial-mesenchymal interface. The results suggest that epithelial-mesenchymal interactions, either through physical interactions and/or through soluble mediators, are necessary for efficient synthesis of collagen VII and biogenesis of the anchoring fibrils.

Cell Communication↗
PubMed1990

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 dermoepidermal 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.

Adult↗
PubMed1990

Epidermolysis bullosa dystrophica inversa in a child.

A 4-year-old child with dystrophic epidermolysis bullosa inversa 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.

Autoantibodies↗
PubMed1990

[Generalized follicular mucinosis].

A patient with generalized follicular mucinosis is presented. On first attendance, the 63-year-old woman had been suffering from generalized pruritus for a year and from general loss of hair for 6 months. The pathognomonic histological features of follicular mucinosis in a histopathological examination of the skin allowed the diagnosis. The lack of a malignant dermal infiltrate and the rapid response to treatment with diamino-diphenylsulphone are, we feel, good prognostic indicators. The histology of alopecia mucinosa, its distinction from the other cutaneous forms of mucinosis by the limitation of mucinous change to the pilosebaceous follicles and the classification of follicular mucinosis into three clinical and prognostic patterns are discussed. The possibility that more widespread disease might be associated with an overt cutaneous lymphoma (mycosis fungoides) is emphasized.

Dapsone↗
PubMed1989

Epidermolysis bullosa simplex with mottled pigmentation.

A patient with epidermolysis bullosa simplex with mottled pigmentation is described. Clinical features include blistering of the skin, especially of the extremities; healing without scars; slight atrophy of the skin; and striking mottled pigmentation of the trunk. Histologic examination of a biopsy specimen from freshly frictioned, clinically uninvolved skin indicated a split inside the basal keratinocytes, focal hyperpigmentation of the basal cells, and pigment incontinence without an inflammatory infiltrate. Indirect immunofluorescence demonstrated focal discontinuity of the basement membrane zone. Electron microscopic examination revealed basal keratinocytes with few intact intracellular organelles, aggregated tonofilaments, and subnuclear splitting with the basal parts of the cells adhering to the basement membrane. Both normal basement membrane and zones of irregular and interrupted structures were seen. Hemidesmosomes and anchoring fibrils appeared to be normal.

Adolescent↗
PubMed1989

Anchoring fibrils and type VII collagen are absent from skin in severe recessive dystrophic epidermolysis bullosa.

Skin of patients with severe generalized recessive dystrophic epidermolysis bullosa (SGRDEB) was studied by immunoelectron microscopy and immunoblotting with antibodies to type VII collagen, a major structural component of anchoring fibrils. In normal skin, the protein was localized to the dermoepidermal junction zone below the basement membrane and was extractable from the papillary dermis after artificial epidermolysis. In SGRDEB skin, neither immunoreactive material below the basement membrane nor identifiable anchoring fibrils could be recognized and neither the tissue form nor the specific proteolytic fragments of type VII collagen were found in extracts of SGRDEB skin. Very low amounts of type VII collagen alpha-chains could be detected in cultures of SGRDEB-fibroblasts, whereas normal fibroblasts synthesized more of this collagen. These results suggest that a genetic defect in the correct synthesis, secretion, or in the molecular assembly of type VII collagen may underlie SGRDEB.

Adolescent↗
PubMed1989

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.

Adult↗
PubMed1988

Lack of type VII collagen in unaffected skin of patients with severe recessive dystrophic epidermolysis bullosa.

Type VII collagen, the major structural component of the anchoring fibrils, was assayed in normal unaffected skin of patients with different forms of hereditary epidermolysis bullosa. Immunofluorescence staining with affinity-purified polyclonal antibodies to type VII collagen revealed a complete absence of staining in the skin of patients with severe dystrophic recessive epidermolysis bullosa. In all other forms, localized recessive dystrophic, dominant dystrophic, junctional and simplex forms there was an intense continuous linear staining of type VII collagen at the dermoepidermal junction. Also, obligate heterozygote carriers of the gene for severe dystrophic recessive form showed a normal pattern of staining. As internal controls and to define the clinical diagnosis, staining with antibodies to type IV collagen, laminin and bullous pemphigoid antigen was also performed. All these antibodies showed a normal staining pattern indicating an intact general morphology of the dermoepidermal junction zone. These results suggest that there is a defect of type VII collagen in patients with severe recessive dystrophic epidermolysis bullosa. The data also suggest that the group of recessive dystrophic epidermolysis bullosa may be heterogeneous not only clinically, but also at the molecular level.

Adolescent↗