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Biomedical subjects

F Wojnarowska

Publications and source records attributed to F Wojnarowska.

At least 199 records · Page 11Linked to original sources

An ultrastructural comparison of dermo-epidermal separation techniques.

Dermo-epidermal separation through the lamina lucida is an essential technique for immunoblotting studies and for the diagnostic immunofluorescence of autoimmune bullous diseases. The most widely used methods of producing skin separation in the laboratory are suction blister induction and incubation in 1 molar sodium chloride. More recently the use of a proteolytic enzyme, thermolysin, has been described for this purpose. We examined the electron microscopic appearance of five suction blisters, five skin specimens separated by 1 M NaCl, and five treated with thermolysin. Both suction blister formation and treatment with 1 M NaCl resulted in a clean separation through the lamina lucida in all specimens examined. However specimens treated with thermolysin developed intra-epidermal separation in four cases without any lamina lucida separation in three. Suction blister formation was associated with hemidesmosome disruption. Incubation in 1 M NaCl remains the most reproducible, convenient, and reliable method of producing dermo-epidermal separation in the laboratory.

Basement Membrane↗

Pemphigus and the terminal hair follicle.

The scalp is frequently involved in the autoimmune skin disease pemphigus. This study demonstrates the distribution of pemphigus antigen in the scalp terminal hair follicle; as well as being found in the epidermis, it is distributed throughout the whole hair follicle outer root sheath and in the dermal bulb matrix cells. The increase in volume of target antigen offered by the follicular epithelium could be a factor determining scalp involvement in pemphigus.

Adult↗

The association of bullous pemphigoid and malignant disease: a case control study.

In a case control study, the incidence of malignant disease in 84 patients with bullous pemphigoid (BP) was compared with 168 controls. The rate of malignant disease (past, concurrent or during follow-up) in BP patients was 17.9% compared to 5.3% in the controls. A number of the malignancies occurring in the BP group may be of doubtful significance, being either temporally very remote or partially attributable to treatment. The rate of concurrent BP and malignancy (within 8 weeks) was 6.0% suggesting that there is probably a slight excess of malignancy in BP, but insufficient to warrant extensive investigation in pursuit of cancer. Comparison of the BP patients with and without cancer identified no clinical or immunopathological subgroups in whom investigations would be indicated. Three patients with both BP and malignancy were HLA-DR 13 positive, which may point to an immunogenetic predisposition to both diseases.

Aged↗

Linear IgA disease of adults: association with lymphoproliferative malignancy and possible role of other triggering factors.

Seventy patients with linear IgA disease of adults were followed up for a mean of 8.5 years and all malignant diseases in this group were ascertained. There were three cases of lymphoproliferative malignancy, which constituted a significant excess over the 0.2 cases that would be expected by comparison with an age- and sex-matched population using National Cancer Registry statistics. In contrast, the non-lymphoid malignancy rate of 13% is almost identical to the expected 14%. A subgroup of 35 of the adult linear IgA disease patients were assessed with respect to the possible precipitating illnesses or drugs, as well as co-existing medical conditions. Almost one-third of patients described an event that was felt could possibly have triggered the linear IgA disease, the most frequent being non-steroidal anti-inflammatory or antibiotic drug therapy, trauma/burns and upper respiratory tract infections. However, it is difficult to determine how often the preceding event is coincidental, and how often, if at all, it is causal.

Adolescent↗

Western blot analysis of the antigen in pemphigoid gestationis.

Using an immunoblotting technique, sera from 25 patients with pemphigoid gestationis were examined and tested against epidermal and dermal extracts of normal skin. The major antigen recognized by seven patients' sera was a molecule of 180 kDa, pemphigoid gestationis antigen, extractable only from the epidermis. Sera from 18 patients with bullous pemphigoid were studied as positive controls and the major antigen recognized was a larger molecule of 220 kDa. There was some degree of shared recognition of antigens with three patients with pemphigoid gestationis recognizing the 220 kDa bullous pemphigoid antigen. In addition one bullous pemphigoid serum recognized the 180 kDa pemphigoid gestationis antigen. The dominant pemphigoid gestationis antigen, however, differs from bullous pemphigoid antigen.

Autoantigens↗

Angina bullosa haemorrhagica--a report of three cases and review of the literature.

Angina bullosa haemorrhagica (ABH) is a term that was first introduced by Badham in 1967 to describe a bullous disorder in which recurrent oral blood blisters appear in the absence of any identifiable systemic disorder. The aetiology of this condition remains obscure. Three cases are described, and their similarities and differences discussed. In one case the histopathology showed an intradermal blister; this feature has not previously been recorded for this condition.

Adult↗

Determination of the optimum site for diagnostic biopsy for direct immunofluorescence in bullous pemphigoid.

The distributions in deposition of immunoreactants in bullous pemphigoid before and after initiating treatment were investigated. Punch biopsies of skin were performed on each patient from up to five different sites and studied by direct immunofluorescence (DIF). Both groups showed the highest diagnostic yield for DIF from perilesional biopsies, with positivity of 78% from the pretreatment group and 83% from the post-treatment group. The percentage of positive DIF for remaining sites in the pre-treatment group were as follows: 50% lower back, 62% oral mucosa, 70% flexor aspect of forearm, 70% anterior aspect of thigh. The post-treatment group had positive DIF of other sites biopsied as follows: 59% anterior aspect of thigh, 64% flexor aspect of forearm, 68% back. We conclude that a single perilesional biopsy is usually sufficient to provide positive DIF and more than two biopsies is seldom justified as it is unlikely to increase the yield of positive DIF. If it is not possible to obtain a perilesional biopsy, then the anterior aspect of thigh or flexor aspect of forearm is a suitable alternative site. If a second biopsy is considered after initiating treatment, it should be taken from the oral mucosa as this has been shown in a separate study to have a higher rate of positive DIF than uninvolved skin.

Aged↗

Use of 1M NaCl split skin in the indirect immunofluorescence of the linear IgA bullous dermatoses.

We compared 1M NaCl split skin with intact skin as substrates for detection of circulating IgA anti-basement membrane (BMZ) antibodies in linear IgA dermatosis (LAD). The sera of 63 patients with LAD including 27 adults and 36 with chronic bullous dermatosis of childhood (CBDC) were examined. 62% of patients overall had circulating IgA anti-BMZ antibodies detectable on intact skin. 73% of patients had circulating antibodies detectable on 1M NaCl split skin as an additional 7 sera were positive. This was a statistically significant increase (p less than 0.01). The sera were mostly positive at a higher titre on the split skin when compared with intact skin. On routine indirect immunofluorescence (IIF) all positive sera produced linear fluorescence on the epidermal side of the split. Twenty serum samples were incubated with split skin overnight; 4 of these specimens exhibited linear fluorescence on the epidermal and dermal sides of the split after this prolonged incubation. These findings suggest that 1M NaCl split skin is a more sensitive substrate for detection of circulating IgA anti-BMZ antibodies in LAD, that these antibodies are heterogeneous and that the target antigen has an epidermal component.

Adult↗

Darier's disease: a focal abnormality of cell adhesion.

Cell adhesion in clinically normal and involved skin in Darier's disease has been investigated using a suction blister technique. We have been unable to detect a subclinical abnormality in cell adhesion which could predispose to the development of acantholytic papules. There may be synthesis of functionally deficient desmosomes, increased breakdown of desmosomes or abnormalities in other adhesion proteins on the surface of the keratinocyte in Darier's disease, but the abnormality in adhesion is focal and restricted to the clinically and histologically abnormal papules.

Acantholysis↗

External ocular findings in lupus erythematosus: a clinical and immunopathological study.

A selected group of 18 patients with systemic lupus erythematosus (SLE) and 30 patients with chronic cutaneous lupus erythematosus (CCLE) showed an unexpectedly high incidence of problems involving the globe or eyelids. Five SLE patients had recurrent episcleritis, two CCLE patients had lower tarsal plaques, and two further CCLE patients had erosion of the lower lid margins associated with conjunctival scarring and symblepharon. This association has not previously been reported. There was an unexpectedly high incidence of deposition of immunoreactants in a linear pattern at the basement membrane zone in normal bulbar conjunctiva, which occurred in both SLE (42%) and CCLE (50%). The significance of these findings is discussed. We believe surface ocular problems in lupus erythematosus to be under-reported and that direct immunofluorescence of bulbar conjunctival biopsy might be helpful in diagnosis.

Adult↗

Identification of the epidermolysis bullosa acquisita antigen by LH 7.2 monoclonal antibody: use in diagnosis.

The sera from two patients with epidermolysis bullosa acquisita were blotted against dermal extracts in comparison with the mouse monoclonal antibody LH 7.2. This antibody reacts with carboxy terminal region of type VII collagen. The epidermolysis bullosa acquisita antisera showed binding to the same molecular weight protein as LH 7.2 confirming that the target antigen for epidermolysis bullosa acquisita antibodies is the carboxy terminal region of type VII collagen. This newly described collagen forms the major component of anchoring fibrils. These findings are consistent with established ultrastructural data which have shown that the epidermolysis bullosa acquisita antigen is located within and below the lamina densa. The monoclonal antibody LH 7.2 provides an internal standard for epidermolysis bullosa acquisita autoantisera activity. The use of immunoblotting of epidermolysis bullosa autoantisera in comparison with the monoclonal antibody LH 7.2 provides definitive investigation for the diagnosis of this disorder.

Adult↗

Immunopathology of the placenta in pemphigoid gestationis and linear IgA disease.

We have investigated the immunopathology of the placenta in bullous diseases by studying the deposition of immune complexes and expression of MHC class II subregion products by immunohistological methods. Placentae from seven patients with pemphigoid gestationis (PG) and two patients with linear IgA disease were studied. In PG immune complexes containing IgGI and C3 were identified in six cases. In linear IgA disease IgAI containing immune complexes were found in both cases. Placentae from patients with PG showed aberrant expression of MHC Class II products. This was not seen in the placentae from patients with linear IgA disease. In PG there was incoordinate expression of the subregion products, DP and DR being more extensively and consistently expressed than DQ. These results and previous immunogenetic studies suggest that PG may be unique among organ specific autoimmune disease, the autoantibodies forming during an allogenic response rather than target cells behaving as antigen presenting cells.

Autoimmune Diseases↗

Skin disease in haemophiliacs with and without antibodies to the human immunodeficiency virus (HIV): further evidence of altered disease behaviour in different risk groups?

Forty-one patients routinely attending the Oxford Haemophilia Centre entered a controlled, blind investigation in order to determine whether HIV antibody status was related to the presence of skin disease. Twenty-four of the 41 patients (58.5%) were HIV antibody positive and none had any general symptoms. Comparison of the HIV antibody positive group with the HIV antibody negative group and with non-haemophiliac controls showed an increased prevalence of four HIV-associated dermatoses: 11 patients had seborrhoeic dermatitis (10 HIV antibody positive and one HIV antibody negative (P less than 0.05 chi 2 test], eight patients had folliculitis (six HIV antibody positive), four patients had mucocutaneous candidiasis, all were HIV antibody positive, and three patients had onychomycosis, all were HIV antibody positive. None of these conditions was seen in a group of 16 non-haemophiliac controls. These findings are different from those reported from a similar study of comparable groups of homosexual men and these results may be further evidence to support the belief that the behaviour of HIV infection differs between haemophiliacs and other risk groups.

Adolescent↗