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M J Cork

Publications and source records attributed to M J Cork.

At least 37 records · Page 2Linked to original sources
PubMed1996

Novel interleukin-1 receptor antagonist exon polymorphisms and their use in allele-specific mRNA assessment.

A variable number of tandem repeats (VNTR) polymorphism has been described in intron 2 of the interleukin-1 receptor antagonist gene. Allele 2 of this polymorphism is associated with many chronic inflammatory diseases. Using direct sequencing of polymerase chain reaction products from individuals of known genotype for the VNTR, we have identified four single base change polymorphisms in exons 1ic and 2 and one upstream of exon 1ic, all of which are probably in linkage disequilibrium with the intron 2 VNTR. The exonic polymorphisms do not alter the encoded amino acid sequence. Using the exon 2 polymorphism as a marker for the intron 2 disease-associated allele, we have been able to analyse allele-specific mRNA in heterozygotic keratinocyte cell lines. The disease-associated allele shows no difference from other alleles in this cell type with respect to mRNA accumulation.

Alleles↗
PubMed1996

Cyclosporine in severe childhood atopic dermatitis: a multicenter study.

BACKGROUND: Severe atopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD. OBJECTIVE: The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD. METHODS: Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales. RESULTS: Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects. CONCLUSION: Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.

Administration, Oral↗
PubMed1996

Genetic control of cytokines. Cytokine gene polymorphisms in alopecia areata.

It is likely that alopecia areata is a multifactorial disease determined by a combination of genetic and environmental factors. The interaction of susceptibility genes with environmental factors gives rise to the disease phenotype, and then genetic modifying factors determine the extent of the inflammatory response and thereby the clinical outcome. Cytokines regulate the inflammatory response. Polymorphisms in these genes may therefore determine the amount of a cytokine that is produced in response to an environmental trigger such as a bacterial or viral infection.

Alopecia↗
PubMed1996

Promoter region polymorphism in the human TNF-alpha gene is not associated with lichen sclerosus.

The pathogenesis of lichen sclerosus remains unknown. However, it has been frequently associated clinically with autoimmunity. The MHC haplotype A1, B8, DR3 is associated with many autoimmune conditions and has also been associated with the uncommon allele of the tumour necrosis factor (TNF-alpha) promoter polymorphism. This allele is also associated with higher production of TNF in vivo and in vitro, and thus it has been speculated that it is the TNF-alpha gene which underlies the genetic association of many diseases with the autoimmune haplotype. There have been many reports of HLA associations with lichen scleroses, but these have not been concordant. We therefore decided to analyse the TNF-alpha polymorphism in patients with lichen scleroses to determine if TNF-alpha was likely to play a role in susceptibility or severity of lichen scleroses. No association between alleles of the TNF-alpha polymorphism and lichen scleroses was found.

Alleles↗
PubMed1995

Comparative genetic association of human leukocyte antigen class II and tumor necrosis factor-alpha with dermatitis herpetiformis.

Dermatitis herpetiformis is a chronic subepidermal vesicular autoimmune skin disease characterized by a strong association with the human leukocyte antigen A1-B8-DR3-DQ2 haplotype. Although the strongest major histocompatibility complex association has been shown to be with the DQw2 (DQB1*0201/DQA1*0501) heterodimer, recent evidence has suggested that there may be up to three susceptibility loci within the major histocompatibility complex. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with a broad range of proinflammatory, immunomodulating, and catabolic activities. We have recently described the first known polymorphism in the human TNF-alpha gene, which is biallelic and lies in the promoter region. The rare allele, TNF2, is in strong linkage disequilibrium with the human leukocyte antigen A1-B8-DR3-DQ2 haplotype. We therefore examined TNF-alpha genotypes in patients with dermatitis herpetiformis and controls and compared the association with that of the class II alleles. Although TNF2 is strongly associated with dermatitis herpetiformis, this was weaker than the association with the class II loci, with DQw2 (DQB1*0201/DQA1*0501) showing the strongest disease association. Of the four patients negative for this marker, only one carried the TNF2 allele. These results indicate that TNF2 is not a major disease susceptibility marker, although our results do not exclude a minor role.

Alleles↗
PubMed1994

Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus.

OBJECTIVE: We have previously described associations between an allele of the interleukin-1 receptor antagonist gene (IL1RN) and several inflammatory diseases. In this study we tested the IL1RN gene as a possible marker in patients with systemic lupus erythematosus (SLE). METHODS: Eighty-one SLE patients and 261 ethnically matched control subjects were genotyped by polymerase chain reaction. RESULTS: We found an increase in both frequency and carriage rate of IL1RN*2 in the SLE group. This association strengthened with extensive disease and particularly with the presence of photosensitivity and discoid skin lesions. CONCLUSION: We describe a novel association between IL1RN*2 and SLE. Carriage of the allele seems to influence severity rather than susceptibility to SLE. We postulate that the association of this polymorphism with disease severity is a widespread feature of common inflammatory and autoimmune diseases.

Base Sequence↗
PubMed1994

Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus.

Cytokines play key roles in immune responses, inflammation and fibrosis. The balance between levels of cytokines, their receptors and specific inhibitors controls inflammatory reactions in tissues. The pathogenesis of lichen sclerosus is unknown but probably involves cytokine mediators such as interleukin 1 (IL-1) and interleukin 1 receptor antagonist (IL-1ra). The IL-1ra is a competitive inhibitor of IL-1 alpha and IL-1 beta, and therefore is a powerful endogenous anti-inflammatory molecule. The gene encoding IL-1ra (designated IL-1RN) has a variable number tandem repeat polymorphism in intron 2. There are five alleles of the gene corresponding to 2, 3, 4, 5 and 6 repeats of an 86-bp sequence. We have determined allele frequencies in a control population and a group of 78 patients with lichen sclerosus. The frequency of one of the alleles is related to increasing disease severity. Thus, IL-1RN may be a candidate gene or severity factor for lichen sclerosus or may possibly be a linked marker to another, as yet undefined, gene.

Alleles↗
PubMed1994

Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene.

One of the most potent pro-inflammatory mediators is the early-acting cytokine interleukin-1. Its actions are regulated by a structurally related anti-inflammatory cytokine known as the interleukin-1 receptor antagonist. We have previously characterized a DNA polymorphism in this gene (IL-1rn) and have found associations between allele 2 and several chronic inflammatory diseases. In the present study, we tested the frequency of allele 2 of the IL-1rn gene in 90 patients with alopecia areata compared with 261 healthy controls. There was a significant association between allele 2 of the polymorphism and the severity of alopecia areata. The frequency of allele 2 increased from 24.1% in the control population to 25.9% in patchy alopecia areata, 36.1% in alopecia totalis, and 47.2% in alopecia universalis (p = 0.005). This severity association is similar to that found in other epithelial-related diseases, including inflammatory bowel disease, lichen sclerosus, and systemic lupus erythematosus.

Alleles↗
PubMed1994

An audit of the value of patch testing: the patient's perspective.

Evaluation of the benefits of patch testing has been difficult. We have attempted to establish patients' views on patch testing and to assess the effectiveness of advice given in the clinic. Postal questionnaires were sent to 135 patients. A total of 105 replies were received (77.8% response rate). 42 patients (40.4%) reported improvement in their skin condition after testing. Of the 43 patients with a final diagnosis of allergic contact dermatitis (ACD), 31 (72%) believed that patch testing had helped. About 1/2 of these were able to avoid the allergens concerned and had made changes in their lifestyle. This contrasts with the group of patients with final diagnoses other than ACD, in whom only 20 of 62 (32%) recorded patch testing as helpful. Similar numbers in both groups had improved sufficiently to be discharged from the clinic. 91 of the patients were entirely correct in their knowledge of the patch test results. 39 felt that the results had not been explained in sufficient detail. This study shows that patch testing is beneficial, especially for those with ACD. Patients' knowledge of the results was good but education could be improved.

Adolescent↗
PubMed1993

Phytophotodermatitis mimicking child abuse.

A 13-month-old girl presented with red finger marks on both shoulders thought initially to be secondary to child abuse. The appearance of the marks was not typical of bruising of the stated age and there were no social concerns or other medical features of child abuse. Direct questioning revealed that the mother had been gardening on a sunny day and had picked the child up prior to the appearance of the marks. The marks are thought to represent a phytophotodermatitis. Many paediatric skin conditions can mimic child abuse. Recognition of this further possibility will prevent avoidable errors of diagnosis.

Child Abuse↗
PubMed1992

Nickel sensitivity: the influence of ear piercing and atopy.

In a group of 612 consecutive patients undergoing routine patch tests for suspected allergic contact dermatitis, more than four-fifths of the 364 women had had their ears pierced, over half gave a history of cutaneous reactions to metallic jewelery and almost one-third were sensitive to nickel. The increase in the frequency of nickel sensitivity in women with pierced ears compared to those with unpierced ears was highly significant (P less than 0.001). In men, nickel sensitivity was much less frequent; occupational factors were often implicated and few cases were related to ear piercing. Jewelery dermatitis was more frequent in atopic than non-atopic women but atopy did not appear to influence the propensity for developing nickel sensitivity in either sex. Ear piercing seems to induce nickel allergy which may result in lifelong morbidity and difficulty in employment. Jewelery suppliers should be encouraged to provide nickel-free earrings to reduce the frequency of this apparently avoidable problem.

Adult↗