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Biomedical subjects

S Burge

Publications and source records attributed to S Burge.

At least 37 records · Page 2Linked to original sources
PubMed1999

Management of Darier's disease.

Darier's disease is an uncommon inherited cutaneous disease which is difficult to manage, especially in adolescence. The warty keratotic papules irritate, smell and look unsightly. Histologically, the condition is characterized by the presence of focal acantholytic dyskeratosis. Treatment is unsatisfactory, particularly in patients with erosive flexural disease, but retinoids reduce the hyperkeratosis. Now the mutation causing Darier's disease has been identified, there is a real possibility of more effective treatment in the future.

Administration, Oral↗
PubMed1999

Toxic epidermal necrolysis and graft vs. host disease: a clinical spectrum but a diagnostic dilemma.

We describe a 53-year-old man who developed partial and full thickness skin loss associated with pyrexia, diarrhoea, liver, renal and bone marrow failure, during treatment for an aggressive B cell lymphoblastic lymphoma. The clinical features and histology were compatible with both toxic epidermal necrolysis and graft vs. host disease, causing a diagnostic and therapeutic dilemma. We discuss the possibility that methotrexate was the causative drug, with review of its cutaneous side-effects. Histologically our patient demonstrated the sparse dermal infiltrate with full thickness epidermal necrosis typical of toxic epidermal necrolysis and graft vs. host disease. We discuss this finding with respect to the pathogenesis of toxic epidermal necrolysis.

Antimetabolites, Antineoplastic↗
PubMed1999

Spectrum of novel ATP2A2 mutations in patients with Darier's disease.

Darier's disease (DD) is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Recently, we identified ATP2A2 encoding the sarco/endoplasmic reticulum Ca(2+)ATPase isoform 2 as the defective gene in DD. Now we report a spectrum of ATP2A2 mutations in 19 families and six sporadic cases with DD and investigate genotype-phenotype correlations. All 21 exons and flanking intron boundaries were amplified and screened for mutations by conformation-sensitive gel electrophoresis and direct sequencing. We identified 24 novel mutations that are scattered throughout the ATP2A2 gene. Two families shared an identical mutation on a common disease-associated haplotype, suggesting inheritance from a common ancestor. The majority of the mutations (54%; 13/24) led to a premature termination codon which further supports the proposal that haploin-sufficiency is a common molecular mechanism for DD. Thirty-eight per cent of mutations (9/24) result in non-conservative amino acid substitutions at highly conserved positions. Two mutations predict mutated polypeptides lacking or carrying additional amino acids. Marked inter- and intrafamilial phenotypic variability of the disease was observed. These results illustrate the considerable diversity of ATP2A2 mutations causing DD and suggest that additional factors are important contributors to the clinical phenotype.

Calcium-Transporting ATPases↗
PubMed1999

ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes.

Darier's disease (DD) is a rare, dominantly inherited disorder that affects the skin producing a variety of types of lesion. Close examination of lesional DD skin shows the presence of abnormal keratinization (epidermal differentiation) and acantholysis (loss of cohesion) of keratinocytes. A number of clinical studies have described the co-occurrence of various neurological and psychiatric symptoms with DD, including mood disorders, epilepsy, mental retardation and a slowly progressive encephalopathy. A single locus for DD has been mapped to chromosome 12q23-q24.1, and a variety of missense, nonsense, frameshift and splicing mutations in the ATP2A2 gene have been described recently in families with DD. This gene encodes the sarcoplasmic/endoplasmic reticulum calcium-pumping ATPase SERCA2, which has a central role in intra-cellular calcium signalling. In this study, we performed mutation analysis on ATP2A2 in 19 unrelated DD patients, of whom 10 had neuropsychiatric phenotypes. We identified and verified 17 novel mutations predicting conservative and non-conservative amino acid changes, potential premature translation terminations and potential altered splicing. Our findings confirm that mutations in ATP2A2 are associated with DD. In neuropsychiatric cases, there was a non-random clustering of mutations in the 3' end of the gene ( P = 0.01), and a predominance of the missense type (70% versus 38% in DD patients). This supports the hypothesis that the DD gene has pleiotropic effects in brain and that mutations in SERCA2 are implicated in the pathogenesis of neuropsychiatric disorders.

Adult↗
PubMed1998

Refined genetic mapping of the darier locus to a <1-cM region of chromosome 12q24.1, and construction of a complete, high-resolution P1 artificial chromosome/bacterial artificial chromosome contig of the critical region.

Darier disease (DD) (MIM 124200) is an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and by abnormal keratinization. We present linkage analysis showing, in four families, key recombination events that refine the location of the DD locus on chromosome 12q23-24.1 to a region of <1 cM. We have constructed a YAC/P1 artificial chromosome (PAC)/bacterial artificial chromosome (BAC)-based physical map that encompasses this refined DD region. The map consists of 35 YAC, 69 PAC, 16 BAC, and 2 cosmid clones that were ordered by mapping 54 anonymous sequence-tagged sites. The critical region is estimated to be 2.4 Mb in size, with an average marker resolution of 37.5 kb. The refinement of the critical interval excludes the ALDH2, RPL6, PTPN11, and OAS genes, as well as seven expressed sequence tags (ESTs) previously mapped in the DD region. The three known genes (ATP2A2, PPP1CC, and SCA2) and the 10 ESTs mapped within the critical region are not obvious candidates for the DD gene. Therefore, this detailed integrated physical, genetic, and partial transcript map provides an important resource for the isolation of the DD gene and, possibly, other disease genes.

Chromosome Mapping↗
PubMed1997

Respiratory symptoms.

Workers with breathlessness or other respiratory symptoms warrant lung function testing with spirometry, which identifies the lung as the cause of the symptoms and separates obstructive lung diseases (mainly asthma and COPD) from restrictive disease (e.g., alveolitis). Occupational health departments should have quality control audits in place for lung function testing. A surveillance questionnaire suitable for use by a responsible person is described.

Adolescent↗
PubMed1997

Breast abscess due to Corynebacterium striatum.

Corynebacterium striatum, a normal constituent of the skin flora, is rarely pathogenic. Previous reports of infection are few, and are mainly confined to immunosuppressed patients or those with indwelling prosthetic devices. We report a case in which the organism caused a recurrent breast abscess in a woman with normal immune function. The only previous reports of Corynebacterium striatum mastitis have been in cows.

Abscess↗
PubMed1997

A novel human papillomavirus identified in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare inherited condition in which there is widespread infection with human papillomavirus (HPV). Patients have a high risk of developing squamous cell carcinoma and Bowen's disease on sun-exposed sites. We describe a Jamaican man with the typical clinical and histopathological features of EV.HPV 8, 24 and a subtype of HPV 38, along with a novel HPV sequence most closely related to HPV 9 have been detected in his skin lesions. Although skin tumours are rare in black patients with EV and he has lived in a temperate climate most of his life, several of the lesions showed bowenoid atypia and he is at risk of developing invasive cutaneous malignancies.

Epidermodysplasia Verruciformis↗
PubMed1997

Changes in CD44 isoform expression during inflammatory skin disease.

The CD44 family of cell surface glycoproteins is widely expressed in epithelial, mesothelial and haemopoietic tissues and is thought to function primarily as adhesion molecules. The molecule has an intracellular, a transmembrane and an extracellular domain. The membrane proximal region of the extracellular domain is of variable structure depending on which of 10 variable exons are involved in coding for this region. Both in vitro stimulated T cells and cytokine stimulated keratinocytes are known to express certain isoforms. In this study we have investigated whether specific isoforms of the CD44 molecule are expressed on epithelial cells and lymphocytes in the course of two inflammatory skin diseases, namely lupus erythematosus and lichen planus. Monoclonal antibodies, specific to the epitopes of the CD44 molecule encoded by v3, v4/5, v6 and v8/9 variable exons and a pan CD44 marker, were used on 10 lupus and 8 lichen planus frozen skin samples and compared with normal skin from 9 different body sites. Results failed to show detectable levels of variant isoforms of CD44 on lymphocytes in either inflammatory skin disease, despite evidence of T cell activation. All CD44 variant isoforms were reduced on the keratinocytes in some sections of lupus and lichen planus. The results are discussed in the context of the current models for the role of CD44 in the immune response.

Humans↗
PubMed1996

Cutaneous tuberculous abscess: a management problem.

A 66-year-old woman presented with a 6-week history of an indolent ulcerating lesion on the anterior chest wall. She had a past medical history of pulmonary tuberculosis which had been treated successfully in 1947. Biopsy of the ulcer showed granulomas and acid-fast bacilli. Cultures grew Mycobacterium tuberculosis, sensitive to all antituberculous drugs. After 7 months of treatment with isoniazid and rifampicin, there was little sign of healing. A sinogram showed a fistula leading into the plombage mass in the left upper lobe. Surgery to remove the plombage and excise the fistula was planned but was rejected by the patient as the risks of this operation are considerable. With continued antituberculous medication the discharge has reduced although the ulcer has not healed.

Abscess↗