Search PubMed⌕ Search

Biomedical subjects

S E Kelly

Publications and source records attributed to S E Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1994

Linear IgA disease and pregnancy.

BACKGROUND: Although many patients with linear IgA dermatosis (LAD) are young and have persistent disease, little is known about the interactions between LAD and pregnancy. OBJECTIVE: Our purpose was to study the effects of LAD on pregnancy, and vice versa. METHODS: Our study included 12 patients with LAD who underwent a total of 19 pregnancies. RESULTS: In all patients the disease improved during pregnancy, enabling therapy to be reduced or stopped. Dapsone was taken by patients during 11 pregnancies, and no adverse effects were seen. No patients had problems in labor. Most patients had a relapse approximately 3 months post partum, even if they had previously been in remission. In two patients, disease started within 3 months of delivery. Fetal outcome was unaffected in all but one fetus, who had a single transient blister. CONCLUSION: We found no contraindication to pregnancy in patients with LAD. We recommend that therapy be reduced or stopped whenever possible during pregnancy and that patients be counseled about the possibility of a relapse post partum.

Adult↗
PubMed1993

Complement polymorphism in herpes gestationis: association with C4 null allele.

BACKGROUND: Herpes gestationis (HG) is a rare, pregnancy-related skin disease characterized by the production of an autoantibody to a component of the hemidesmosome. It is associated with the class II antigens HLA-DR3 and HLA-DR4, but its potential association with the "class III antigens" C2, C4, and factor B has not previously been studied. OBJECTIVE: Our purpose was to study complement polymorphism in HG. METHODS: Using electrophoresis and immunofixation techniques, we determined the allele frequencies of C4A, C4B, C3, and factor B in 42 patients with a history of HG. RESULTS: Ninety percent of patients carried a C4 null allele (C4*QO). No statistically significant association with C3 or factor B alleles was seen. CONCLUSION: HG is associated with the presence of a C4*QO. Whether the C4*QO is the primary genetic association, or whether the C4*QO is related to its linkage disequilibrium with DR3 and DR4 has yet to be determined.

Adult↗
PubMed1993

Anti-HLA antibodies in pemphigoid gestationis (herpes gestationis).

Pemphigoid gestationis (PG; herpes gestationis) is a rare autoimmune disease associated with pregnancy, currently defined by the presence of complement deposition along the cutaneous basement membrane zone. It is known to be associated with HLA-DR3 and DR4, and an increase in anti-HLA antibodies in those with a history of PG has been reported. We have studied 39 patients with an immunofluorescence-confirmed diagnosis of PG for the presence and specificity of anti-HLA antibodies. Anti-HLA antibodies were found in all 39 patients. Specificity was against class I antigens in 98% (controls 10%; P < 0.001) and class II antigens in 25% (controls 8.5%; P < 0.001). Almost all anti-HLA antibodies were cytotoxic. The universal presence of anti-HLA antibodies in PG suggests that they may develop coincidently with antibasement membrane antibodies, and may reflect a common immunological event.

Adult↗
PubMed1992

Isolated basal keratinocytes express pemphigoid gestationis antigen.

Basal keratinocytes were isolated from epidermal cell suspensions prepared by trypsinization of normal human skin. Cells were identified as basal cells by their adherence to collagen and confirmed as basal cells by the presence of pemphigoid antigen. Using an indirect immunofluorescence assay, cells were found to express pemphigoid gestationis-related antigen. Sera from patients with pemphigoid gestationis reacted in one of two immunofluorescence patterns: either polar, in a pattern similar to that observed with bullous pemphigoid serum, or with uniform staining around the cell periphery. Pemphigoid gestationis-related antigen is expressed by isolated basal keratinocytes and is resistant to trypsinization. The heterogeneity of immunofluorescence patterns may correspond to the heterogeneity of antigen recognition by different patients with pemphigoid gestationis.

Antigens↗
PubMed1991

Morphological evidence for calcium-dependent association of calgranulin with the epidermal cytoskeleton in inflammatory dermatoses.

The association of calgranulins, intracellular calcium-binding proteins, with the keratinocyte cytoskeleton has been studied. These molecules are expressed in various inflammatory dermatoses and in organ-culture explants. Triton X-100 extraction in the presence of calcium or EDTA suggested that calgranulins are detergent insoluble in the presence of calcium. The molecules were localized in a plaque-like structure at the cell periphery in lesional skin and in organ-culture explants. Following induction of calgranulins in vitro there was a redistribution of the intermediate filament cytoskeleton into a perinuclear halo, although desmosomes remained intact. These various features suggest that these members of the S-100 protein family have a role in cytoskeletal changes seen in various skin diseases.

Blotting, Western↗
PubMed1991

Probing the nature of chromosomal DNA-protein contacts by in vivo footprinting.

Of the various approaches employed to unravel the mechanisms of gene regulation, the method of in vivo footprinting seems likely to be increasingly perceived as indispensable. A clear knowledge of the actual pattern of DNA-protein interactions occurring at a given gene within a cell, gained from data obtained with a minimum of external perturbation, can provide a benchmark against which attempts at in vitro reconstruction of the relevant interactions can be judged. This appears particularly important given our current awareness of the degeneracy displayed by certain DNA sequences in terms of their in vitro ability to separately bind to more than one (sometimes several) species of protein factor present in a nuclear extract. The mutual pursuit of both in vivo and in vitro approaches will likely provide the best route to a detailed molecular description of regulatory interactions. Following the introduction of both improved and novel technical approaches, the possibility of probing chromosomal DNA-protein associations at nucleotide resolution is now well within the capacity of most laboratories. In this article the techniques of, probing reagents used for, and some important results obtained by in vivo footprinting are critically discussed.

Animals↗
PubMed1990

Calgranulin expression and association with the keratinocyte cytoskeleton.

The molecules calgranulin A and B are two intracellular calcium-binding proteins which are expressed by the lesional keratinocytes of inflammatory dermatoses. We have investigated the induction of the calgranulin proteins in an in vitro system and characterized the epidermal form of calgranulin. Using calgranulin-specific monoclonal antibodies, we have shown that these proteins are expressed within the epidermis of skin explants after 12-24 h culture in vitro. The induction of calgranulin-specific staining on culture was prevented, however, by the inclusion of cycloheximide in the culture medium, in sufficient quantities to prevent de novo protein synthesis. Indirect immunofluorescence staining was used to analyse the subcellular localization of the calgranulin proteins. The specific staining pattern with antibodies which recognize the individual calgranulin proteins was retained in detergent insoluble cytoskeletal preparations of epidermis. In Western blotting experiments epidermal calgranulins could be solubilized only by using a urea-based protein extraction buffer. After sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the epidermal extracts a single antigen, with a molecular weight of 13.0 kD was detected with the calgranulin-specific antibody MAC 387. The expression of calgranulins, similar to other members of the same protein family, may regulate cytoskeletal changes in skin disease.

Blotting, Western↗
PubMed1990

Antigen-presenting cells in the skin and placenta in pemphigoid gestationis.

In pemphigoid gestationis (PG), one of the major initiating events is the aberrant expression of the class II molecules of the major histocompatibility complex in the placenta. We used a panel of 13 monoclonal antibodies to investigate the phenotype of the MHC class II positive antigen-presenting cells (APC) in the skin and placenta in PG. In the skin, the APC show reactivity with a variety of macrophage markers and the CDI marker of Langerhans cells. By contrast, the MHC class II positive cells in the placenta showed no reactivity with macrophage or Langerhans cell markers, but were the cytokeratin-positive trophoblast or vimentin-positive stromal cells.

Antigen-Presenting Cells↗
PubMed1990

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↗
PubMed1989

Calgranulin expression in inflammatory dermatoses.

We have used monoclonal antibodies to study the expression of calgranulins by keratinocytes in inflammatory dermatoses. Calgranulins are intracellular calcium binding proteins which have inflammatory cytokine activity and are composed of at least two different chains, calgranulin A and B. Antibody CF 145 and CF 557 identify calgranulin A and B, respectively. MAC 387 recognizes a molecule probably containing both calgranulins. Keratinocytes in normal skin did not contain these molecules. The keratinocytes in 52 cases of different inflammatory dermatoses showed expression of both calgranulin chains in lesional but not in non-lesional skin. Keratinocytes in inflammatory dermatoses therefore express an intracellular calcium binding protein which has cytokine activity.

Antibodies, Monoclonal↗
PubMed1989

The distribution of IgG subclasses in pemphigoid gestationis: PG factor is an IgG1 autoantibody.

Using monoclonal antibodies in immunofluorescence techniques, the subclass distribution of anti-basement membrane zone IgG antibodies was studied in the skin, placenta, and serum of patients with pemphigoid (herpes) gestationis. IgG1 was found to be the major IgG subclass in both serum and tissue, being detected in the sera of all pemphigoid gestationis patients studied. In pemphigoid and pemphigus, however, the distribution of IgG subclasses was heterogeneous, with IgG4 being the dominant autoantibody. Pemphigoid (herpes) gestationis factor, the circulating anti-basement membrane zone autoantibody thought to be pathogenic in pemphigoid gestationis, is therefore, an IgG1 antibody, with inferred complement binding capacity. Tissue damage in pemphigoid gestationis is apparently mediated by complement fixation which is detected via the classical complement cascade.

Autoantibodies↗
PubMed1989

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↗
PubMed1989

Perturbation of chromatin architecture on ecdysterone induction of Drosophila melanogaster small heat shock protein genes.

Alterations in the pattern of DNase I hypersensitivity were observed on ecdysterone-stimulated transcription of Drosophila melanogaster small heat shock protein genes. Perturbations were induced near hsp27 and hsp22, coupled with an extensive domain of chromatin unfolding in the intergenic region between hsp23 and the developmentally regulated gene 1. These regions represent candidates for ecdysterone regulatory interactions.

Animals↗