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Biomedical subjects

J A Hunter

Publications and source records attributed to J A Hunter.

At least 19 recordsLinked to original sources
PubMed1999

Psoriatic keratinocytes show reduced IRF-1 and STAT-1alpha activation in response to gamma-IFN.

Psoriasis is a chronic inflammatory dermatosis characterized by hyperproliferative keratinocytes (KC). The skin lesions are infiltrated by T cells, which secrete gamma interferon (gamma-IFN) and are believed to be necessary to maintain the psoriatic phenotype. In normal KC, gamma-IFN is a potent inhibitor of proliferation, but proliferation of KC persists in psoriatic plaques despite the presence of gamma-IFN. Immunostaining of interferon regulatory factor-1 (IRF-1) revealed that IRF-1 was localized to the basal cells of the epidermis in normal and in nonlesional psoriatic skin, but was suprabasal or completely absent in lesional psoriatic skin. This finding led to the hypothesis that abnormal signaling in the gamma-IFN pathway may occur in psoriatic KC. To test this hypothesis, we measured activation of IRF-1 and signal transducer and activator of transcription (STAT)-1alpha transcription factors in KC after stimulation with gamma-IFN. Primary cultures of KC from normal and nonlesional psoriatic skin were stimulated with gamma-IFN and subsequent transcription factor activation was measured by electrophoretic mobility shift assay. Psoriatic KC showed a reduced induction of IRF-1 and STAT-1alpha activation after stimulation with gamma-IFN, compared with normal KC. Reduced activation of IRF-1 and STAT-1alpha in response to gamma-IFN indicates a fundamental defect in the growth and differentiation control of psoriatic KC in the absence of the influence of other cell types.

Adult↗
PubMed1998

Differential expression of selenoproteins by human skin cells and protection by selenium from UVB-radiation-induced cell death.

The generation of reactive oxygen species has been implicated as part of the mechanism responsible for UVB-radiation-induced skin damage. In mice, evidence suggests that increased dietary selenium intake may protect skin from many of the harmful effects of UVB radiation. We sought to determine the selenoprotein profile of cultured human skin cells and whether selenium supplementation could protect keratinocytes and melanocytes from the lethal effects of UVB radiation. Labelling experiments using [75Se]selenite showed qualitative and quantitative differences in selenoprotein expression by human fibroblasts, keratinocytes and melanocytes. This was most noticeable for thioredoxin reductase (60 kDa) and phospholipid glutathione peroxidase (21 kDa); these proteins were identified by Western blotting. Despite these differences, we found that a 24 h preincubation with sodium selenite or selenomethionine protected both cultured human keratinocytes and melanocytes from UVB-induced cell death. With primary keratinocytes, the greatest reduction in cell death was found with 10 nM sodium selenite (79% cell death reduced to 21.7%; P<0.01) and with 50 nM selenomethionine (79% cell death reduced to 13.2%; P<0.01). Protection could be obtained with concentrations as low as 1 nM with sodium selenite and 10 nM with selenomethionine. When selenium was added after UVB radiation, little protection could be achieved, with cell death only being reduced from 88.5% to about 50% with both compounds. In all of the experiments sodium selenite was more potent than selenomethionine at providing protection from UVB radiation.

Cell Division↗
PubMed1998

Desmoglein in multiple self-healing squamous epithelioma of Ferguson-Smith--comparison of staining patterns with actinic keratoacanthoma and squamous cell carcinoma of the skin.

BACKGROUND: Multiple self-healing squamous cell epithelioma of the skin (MSSE) is the most common variant of multiple keratoacanthoma. Although the morphology of the lesions in MSSE is similar to classical actinic keratoacanthoma (KA), several distinctive features in clinical presentation and histology have been emphasized. Desmosomes have been shown to be downregulated in certain types of carcinoma. Desmogleins (Dsg) are transmembrane desmosomal glycoproteins that exist as three isoforms. Dsg markers have been found to be reduced or absent in squamous cell carcinoma (SCC) but preserved in KA. OBJECTIVE: This study was designed to determine the pattern of Dsg staining in MSSE. METHODS: Eight tumors from two female patients with MSSE were stained with the antidesmoglein monoclonal antibody 32-2B, which recognizes Dsgl and Dsg3. RESULTS: All eight tumors showed uniform pericellular Dsg staining throughout the nonkeratinized layers of the neoplastic epithelium. This pattern is entirely similar to that observed in actinic KA, normal epidermis or follicular epithelium. CONCLUSION: Despite the differences, uniform preservation of Dsg seems to be the invariable feature of both MSSE and KA. Further studies are necessary to evaluate this antibody in routine dermatopathology of MSSE and SCC.

Aged↗
PubMed1998

Ichthyosiform erythroderma associated with generalized pustulosis.

Two unrelated boys are described who were born as collodion babies and subsequently developed non-bullous ichthyosiform erythroderma and flares of generalized sterile pustulosis, similar to generalized pustular psoriasis. Both patients had a good response to treatment with oral retinoids.

Acute Disease↗
PubMed1998

The characteristics of urticaria in 390 patients.

Data were collected on 390 patients who attended a dermatology out-patient department in whom a clinical diagnosis of urticaria was made. Two hundred and thirty-seven (61%) were women. The median age at onset of symptoms was 40 years. Sixty-one (16%) had acute urticaria with symptoms of less than 6 weeks duration at presentation. The disorder was deemed idiopathic in 217 (56%) patients, 59 (15%) had physical urticaria and 57 (15%) had both idiopathic and physical urticaria. Thirty-eight (10%) patients reported intolerance to salicylate or similar drugs, and 31 of these 38 patients also had idiopathic symptoms. One hundred and seventy-two (44%) patients reported a good response to treatment with H1 receptor antagonists. Those who gained little or no benefit from these drugs were more likely to have a physical urticaria (P < 0.05) or to report intolerance reactions (P < 0.05). Only 113 (29%) patients were asymptomatic when discharged. One in five of a small sample contacted still had symptoms 10 years after presentation. Patients seen in an urticaria clinic were less likely to have routine investigations performed and more likely to be discharged at first attendance. When compared with previous published surveys, these figures show a lower proportion of intolerance reactions and a greater proportion of patients responding well to treatment with antihistamines.

Acute Disease↗
PubMed1998

Epidermal Langerhans cell apoptosis is induced in vivo by nonanoic acid but not by sodium lauryl sulphate.

Exposure to irritants may cause chronic irritant contact dermatitis (ICD), characterized by irregular epidermal thickening and a predominantly dermal mononuclear cell infiltrate. The mechanisms involved, and why only certain individuals are affected, are not clearly understood. Different irritants may trigger different cellular and molecular interactions between resident skin cells and recruited inflammatory cells. In some individuals these interactions may become self-perpetuating resulting in persistent inflammation in the absence of continued exposure. This study examined Langerhans cell (LC) density in clinically normal skin of 46 patients with chronic ICD and 10 healthy individuals, and compared the action of the two irritants nonanoic acid (NA) and sodium lauryl sulphate (SLS) on the LCs and keratinocytes of clinically normal skin in patients with chronic ICD. There was a higher number of LCs/mm basement membrane in patients compared with controls, although there was no difference in the number of dendrites/LC nor in dendrite length. SLS induced keratinocyte proliferation after 48 h exposure, had no effect on LC number or distribution, and induced keratinocyte apoptosis after 24 and 48 h exposure. In contrast, NA decreased keratinocyte proliferation after 24 h exposure but this returned to basal levels after 48 h, and induced epidermal cell apoptosis after only 6 h exposure. NA dramatically decreased LC number after 24 and 48 h exposure, which was accompanied by basal redistribution and decreased dendrite length. Most significantly, NA induced apoptosis in over half of the LCs present after 24 and 48 h exposure.

Adolescent↗
PubMed1998

Familial halo naevi.

The incidence of halo naevi in the population has been estimated to be 1%. We now report the simultaneous occurrence of such naevi in four members of a family previously resident in New Zealand.

Adolescent↗
PubMed1998

Injection of the rheumatoid knee: does intra-articular methotrexate or rifampicin add to the benefits of triamcinolone hexacetonide?

OBJECTIVE: Does the addition of 600 mg rifampicin or 50 mg methotrexate improve pain relief after injection of the rheumatoid knee with 20 mg triamcinolone hexacetonide (TH)? METHODS: Eighty-two patients on stable therapy were allocated at random to receive intra-articular TH alone, TH and methotrexate (TH+M) or TH and rifampicin (TH+R). Pain was recorded by a weekly chart and analysed using the area under the curve (AUC), periods of total pain relief and duration of effect. Examinations and microwave thermography were performed by an independent meteorologist at baseline, 3 and 6 months. RESULTS: Using the AUC, pain was significantly better in the TH+R group compared with TH alone (P=0.039, Mann Whitney U). The median duration of improved pain scores was 13.5 weeks with TH alone, 10 with TH+M and 19 with TH+R. Examination and microwave thermography revealed improvements compared with baseline, but there were no significant differences between the groups. Eleven of 28 patients treated with TH + R developed a flare of post-injection pain. CONCLUSIONS: Whilst the addition of rifampicin improved pain relief, the occurrence of pain after injection remains a problem. Measures to minimize this are needed when TH+R is used.

Aged↗
PubMed1997

Cutaneous malignant melanoma in Scotland: incidence, survival, and mortality, 1979-94. The Scottish Melanoma Group.

OBJECTIVE: To determine the changing incidence of and mortality from cutaneous malignant melanoma in Scotland from 1979 to 1994. DESIGN: Detailed registration of clinical and pathological features, surgical and other treatment, and follow up of all cases of cutaneous malignant melanoma diagnosed from 1979 to 1994 and registered with specialist database for Scotland. SETTING: Scotland. SUBJECTS: 6288 patients with invasive primary cutaneous malignant melanoma diagnosed between 1 January 1979 and 31 December 1994. RESULTS: The annual age standardised incidence of cutaneous malignant melanoma rose significantly from 3.5 to 7.8 per 100,000 per year in men and from 6.8 to 12.3 per 100,000 per year in women (P < 0.001 for both). World standardised rates increased from 2.7 to 6.0 per 100,000 per year in men and 4.6 to 8.50 per 100,000 in women. The incidence of melanoma continued to increase significantly in men of all ages during the study, but the rate stabilised in women after 1986. Mortality from cutaneous malignant melanoma was 1.3 per million per annum in men in 1979, rising to 2.3 per million per annum in 1994 (P < 0.01); it was 2.4 per million per annum in women in 1979, falling to 1.9 per million per annum in 1994 (P = 0.09). The underlying mortality trends showed a continuing rise for men but a downward trend for women that was not significant (P = 0.09). In men, melanoma free survival was 69% at 5 years and 61% at 10 years; in women the corresponding rates were 82% and 75%. Younger patients had higher survival rates, which were not entirely explained by thinner tumours. Over the 15 year period, survival rates improved by 12% overall, only partly owing to thinner tumours. CONCLUSIONS: In Scotland the incidence of melanoma in women has stabilised, while mortality associated with melanoma in women shows a downward trend.

Adolescent↗
PubMed1997

Renal allograft recipients with high susceptibility to cutaneous malignancy have an increased prevalence of human papillomavirus DNA in skin tumours and a greater risk of anogenital malignancy.

Renal allograft recipients (RARs) have a well-documented increased incidence of viral warts and cutaneous neoplasia, particularly those with long graft life and high sun exposure. A clinicopathological survey of 69 RARs in south-east Scotland, with follow-up periods of up to 28 years after transplantation, revealed marked variation in patient susceptibility to cutaneous malignancy with concomitant variation in HPV prevalence. Skin cancers were found in 34 patients. Eight patients showed high susceptibility [defined as more than four intraepidermal carcinomas (IECs) or invasive squamous cell carcinomas (SCCs)] 42 had intermediate susceptibility (1-3 IECs or SCCs, or >3 keratoses) and 18 had low susceptibility (< or = 3 keratoses and no cancers). SCCs, IECs and keratoses from the high-susceptibility group were found to have greater prevalences of human papillomavirus (HPV) DNA (56%, 45% and 50% respectively), than SCCs (0%) and IECs (33%) from intermediate-susceptibility RARs and keratoses (36%) from the combined intermediate- and low-susceptibility groups and compared with a group of immunocompetent controls (27%, 20% and 15% respectively). No differences in p53 protein accumulation, determined immunohistochemically, were observed in tumours from the three groups. Categorization of RARs by susceptibility to cutaneous malignancy provides clinically useful information, as significantly more high-susceptibility patients (38%) developed aggressive, potentially lethal anogenital or cutaneous squamous cell cancers than did patients in the intermediate group (5%, P=0.005) or the low-susceptibility group (0%).

Adult↗
PubMed1997

Atopic and non-atopic individuals react to nickel challenge in a similar way. A study of the cytokine profile in nickel-induced contact dermatitis.

The influence of atopy on delayed-type hypersensitivity remains unclear. The expression of cytokine mRNA was assessed by reverse transcription-polymerase chain reaction (RT-PCR) in biopsy skin taken 24 h after the application of a 5% NiSO4 patch to five patients with atopic dermatitis and seven non-atopic subjects with previously proven contact allergy to nickel. Control specimens were obtained from untested and vehicle-tested skin from the same individuals. There was a significant increase in the mRNA expression for interferon-gamma (IFN-gamma), interleukin (IL)-2 and IL-4 together after nickel challenge in both patients (analysis of variance P = 0.007) and non-atopic-individuals (P = 0.005). In contrast, IL-10 mRNA increased in the non-atopic group only. These results show that atopic patients and normal subjects have a similar immunological reaction to nickel challenge. Moreover, it is suggested that both Th1- and Th2-type cytokines are involved in the immunopathogenesis of contact dermatitis.

Adult↗
PubMed1997

Leukaemia inhibitory factor: induction in the early phase of allergic contact dermatitis.

It has been suggested that leukaemia inhibitory factor (LIF), may be involved in the pathogenesis of cutaneous inflammation. In 5 patients with previously proven contact allergy to nickel, LIF mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction and immunohistochemistry in 5% nickel sulfate patch test biopsies 24 h after application of the patch. Control specimens were obtained from non-tested and vehicle-tested skin from the same individuals. LIF mRNA expression was significantly increased in nickel-tested skin compared with both vehicle-tested (p = 0.045) and non-tested skin (p = 0.041). All biopsies showed similar patterns of LIF immunoreactivity, with no significant differences between nickel-tested, vehicle-tested and non-tested skin. Immunostaining was cytoplasmic and was present in the epidermis and hair follicles. No dermal staining was observed. This study suggests that LIF may play a role in the early phase of allergic contact dermatitis.

Adult↗
PubMed1997

Intergroup bias and self-evaluation: domain-specific self-esteem, threats to identity and dimensional importance.

Recent theoretical statements argue that two predictions about self-esteem and intergroup bias may be derived from social identity theory. The first suggests that in-group bias enhances self-esteem. The second suggests that threats to self-esteem enhance in-group bias. Previous research has provided little firm evidence for either prediction. Much of this work has, however, tended to ignore realistic groups, domain-specific self-esteem, the assessment of self-esteem prior to and following the display of in-group bias and the importance attached to evaluative dimensions. The current investigation sought to redress these issues. In separate experiments, men and women presented with positive and negative feedback, evaluated in-group and out-group success and failure on dimensions important and unimportant to the in-group. Women displayed out-group bias on dimensions unimportant to their in-group (i.e. physical ability) with respect to evaluations of failure. Women subsequently manifested a decrease in physical self-esteem. Men displayed in-group bias on dimensions unimportant to their in-group (i.e. verbal ability) and, following positive feedback, on dimensions important to the in-group (i.e. physical ability). Men subsequently manifested an increase in verbal and physical self-esteem. Global self-esteem was unaffected in each study. These findings suggest that the relative display of bias can affect domain-specific self-esteem. No support was found for the postulate that low or threatened self-esteem can enhance bias on evaluative dimensions important to the in-group.

Ego↗
PubMed1997

Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis.

OBJECTIVE: To determine the effect of intramuscular gold and oral hydroxychloroquine (HCQ) on the lipid profile of patients with rheumatoid arthritis (RA). METHOD: A prospective randomised clinical trial of 12 months' duration was performed in 100 RA patients. Data on clinical and laboratory parameters of disease activity, and fasting serum lipid samples was collected at baseline and at three monthly intervals over one year. RESULTS: The expected second line response was seen with no significant difference in efficacy between the groups at 12 months. The HCQ group had a significant overall improvement in their lipid profile while there was a trend for lipid profiles in the gold group to worsen. CONCLUSIONS: HCQ is an effective second line agent that has beneficial effects on serum lipids. This should be taken into account when choosing a disease modifying anti-rheumatic drug in patients who suffer from RA and who have significant cardiovascular risk factors.

Adult↗
PubMed1997

Measurement of quality of life in atopic dermatitis: correlation and validation of two different methods.

Atopic dermatitis is a chronic relapsing condition that can have considerable effects on the lives of sufferers. It is apparent that good, valid measures of life quality are necessary for quantifying the patients' perspective of the severity of their disease and the Dermatology Life Quality Index is often employed in clinical research. In a community study of atopic dermatitis we have assessed disability using the Dermatology Life Quality Index and the Patient Generated Index and compared the results from both indices. The results were significantly correlated and reflected the range of disability in patients in the community. Some items of the Dermatology Life Quality Index were not relevant for atopic dermatitis patients in the community and others, including swimming and sleep loss, were often cited in the Patient Generated Index but are not included in the Dermatology Life Quality Index. The Patient Generated Index is a novel, flexible approach to quality of life measurement that may be suitable for reflecting the wide variety of disability that is experienced by dermatological patients.

Activities of Daily Living↗