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Biomedical subjects

A P Black

Publications and source records attributed to A P Black.

15 recordsLinked to original sources
PubMed2006

The role of skin-homing T cells in extrinsic atopic dermatitis.

BACKGROUND: T cells that express Cutaneous Lymphocyte-Associated antigen (CLA) have the potential of migrating to the skin, and are hypothesized to play a role in cutaneous atopic disease. AIM: To investigate the immune phenotype and cytokine responses to Der p 1 stimulation of CLA+ T cells in extrinsic atopic dermatitis (EAD). DESIGN: In vitro testing, with controls. METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from EAD patients (n=27) and non-atopic healthy individuals (n=22). Phenotypic analysis of naive, CLA+ and non-CLA+ memory/effector CD4+ and CD8+ T cells used markers of cell activation, differentiation, adhesion, apoptosis and chemokine receptor expression. Cytokine responses in these cells were studied following Der p 1 stimulation. RESULTS: CLA+ T cells from EAD patients expressed significantly higher levels of CD25, HLA-DR, CD38, CD71, CXCR1, CXCR2 and lower levels of bcl2, CCR5, CCR7, CXCR3, and CD62L (p<0.05). DISCUSSION: In EAD patients, CLA+ T cells express increased levels of markers associated with activation, adhesion and apoptosis, show differences in the level of expression of differentiation markers and display a distinct chemokine receptor preference, compared with cells from healthy controls. These data suggest a significant role for CLA+ T cells in the pathogenesis of cutaneous atopic disease.

Adult↗
PubMed2006

Severe atopic dermatitis is associated with a reduced frequency of IL-10 producing allergen-specific CD4+ T cells.

BACKGROUND: Several studies have investigated levels of T-cell-derived interleukin (IL)-10 in individuals with atopic dermatitis, with conflicting results. AIMS/HYPOTHESIS: In order to address whether stratification of disease severity may help resolve the different findings, the hypothesis was tested that individuals with severe atopic dermatitis have a lower frequency of circulating IL-10-producing, allergen-specific CD4+ T cells than do individuals with mild disease. METHODS: Using peripheral blood mononuclear cells derived from individuals with severe (n=12) and mild atopic dermatitis (n=10) and from nonatopic controls (n=10), we investigated production by CD4+ T cells of tumour necrosis factor (TNF)-alpha, IL-4, IL-5, IL-13 and IL-10 in response to phorbol myristate acetate/ionomycin and Der p1 allergen. RESULTS: It was observed that there were significantly higher frequencies of allergen-specific circulating CD4+ T cells producing TNF-alpha- IL-4-, IL-5- and IL-13, and lower frequencies of these cells producing IL-10 in individuals with severe atopic dermatitis compared with mildly affected individuals and nonatopic controls (P<0.01 for all comparisons). Furthermore, the Der p1-specific CD4+ T cells were enriched within the subset of cells positive for cutaneous lymphocyte-associated antigen. CONCLUSIONS: Analysis of levels of allergen-specific CD4+ T-cell production of IL-10 in relation to disease severity argues in favour of a role for IL-10 in the control of atopic dermatitis.

CD4-Positive T-Lymphocytes↗
PubMed2005

p53-specific CD8+ T-cell responses in individuals with cutaneous squamous cell carcinoma.

BACKGROUND: Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence that the immune response is important in the control of cutaneous SCC, there are no studies documenting potential tumour-associated antigens. OBJECTIVES: We tested the hypothesis that individuals with cutaneous SCC have functional circulating CD8+ T cells specific for p53. METHODS: Interferon-gamma immunosorbent assays were used to screen peripheral blood mononuclear cells for reactivity to six p53-derived HLA-A*0201-restricted epitopes from HLA-A*0201-positive patients and controls. RESULTS: We observed significantly elevated frequencies of p53-specific CD8+ T cells in seven of 26 individuals with cutaneous SCC and in one of 10 controls. The degree of lymphocytic infiltrate significantly correlated with the frequency of CD8+ T cells specific for p53 epitopes, but not with control epitopes. CONCLUSIONS: Overall, these data suggest that p53 may represent a target for CD8+ T cells in a proportion of individuals with cutaneous SCC.

CD8-Positive T-Lymphocytes↗
PubMed2005

Interleukin-4 induced down-regulation of skin homing receptor expression by human viral-specific CD8 T cells may contribute to atopic risk of cutaneous infection.

Factors controlling the expression of cutaneous lymphocyte-associated antigen (CLA) by T cells are poorly understood, but data from murine and human CD4(+) T cell systems have suggested that cytokines play an important role. However, there are no data examining the influence of cytokines on the expression of CLA by human antigen-specific CD8(+) T cells. Peripheral blood mononuclear cells (PBMC) were isolated from 10 HLA-A*0201-positive healthy individuals. Using HLA-peptide tetrameric complexes refolded with immunodominant peptides from Epstein-Barr virus (EBV), cytomegalovirus (CMV) and influenza A virus, we investigated the temporal associations of CLA expression by viral-specific CD8(+) T cells following stimulation with antigen. Ex vivo influenza matrix-specific CD8(+) T cells expressed significantly (P < 0.05) greater levels of CLA than EBV BMLF1 and CMV pp65-specific CD8(+) T cells (mean 9.7% influenza matrix versus 1.4% BMLF1 versus 1.1% pp65) and these differences were sustained on culture. However, regardless of viral specificity, interleukin (IL)-12 and IL-4 induced significant (P < 0.05) dose-dependent up-regulation and down-regulation of CLA expression, respectively, with IL-4 showing a dominant negative effect. In many cases, IL-4 resulted in complete abrogation of detectable CLA expression by the viral-specific CD8(+) T cells. Overall these data demonstrate that CLA expression by human viral-specific CD8(+) T cells is highly dynamic and that IL-4 causes significant down-regulation. Disorders associated with a type 2 cytokine shift may reduce the efficiency of skin homing by viral-specific CD8(+) T cells. Furthermore, the ability to modify the local and systemic microenvironment may offer novel therapeutic strategies that influence tissue-specific T cell homing.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2002

An analysis of maternal and fetal hair lead levels.

Lead contamination of the environment is an important public health consideration. There is evidence of declining blood lead levels in Britain, however, there is still concern about chronic exposure of the fetus and young children to low levels of lead and the effect that this has on neurodevelopment. Hair lead levels have been found to correlate well with body lead contamination. This study is the first to document the level of hair lead in pregnant women and their babies from an urban British population. There was no evidence of toxic maternal lead levels and the fetus is protected by the placental barrier.

Adult↗
PubMed1996

Relationship between physical signs of elbow dysplasia and radiographic score in growing Rottweilers.

OBJECTIVE: To examine the relationship between physical signs of elbow dysplasia and radiographic appearance of the elbow joints in growing dogs. DESIGN: Prospective study. ANIMALS: 55 Rottweiler pups. PROCEDURE: Owners of clinically normal Rottweiler pups were contacted through breed clubs in 3 Australian states and asked to participate in the study. All those offering to participate were included. PROCEDURE: The first physical examination was performed when pups were 3 months old and included a lameness evaluation and palpation of the elbow joints. Physical examinations were repeated when pups were 5, 6, 9, and 12 months old. Radiographs of the elbows were obtained at 6 and 12 months. Relationships among lameness, decreased range of movement, signs of pain, and radiographic data related to elbow dysplasia were examined. RESULTS: Elbow dysplasia caused clinical lameness in only 3 dogs but 57% of dogs developed radiographic signs of elbow dysplasia by 12 months of age. A grade-2 radiographic score at 12 months of age was significantly associated with clinical elbow dysplasia. CLINICAL IMPLICATIONS: Elbow dysplasia has a prevalence of > 50% in certain breed populations. This study supports radiographic screening at 12 months of age, accompanied by physical examination to detect clinical elbow dysplasia.

Age Factors↗
PubMed1992

Incidence and clinical significance of sesamoid disease in rottweilers.

A group of 55 rottweiler pups was studied from three to 12 months old to assess the incidence and clinical significance of disease involving the palmar metacarpal sesamoid bones. The results of physical examination were correlated with clinical signs of lameness and the results of radiographic examination of the forefeet. Twenty-one dogs became lame during the study and in 12 of them the lameness was attributable to sesamoid disease. However by 12 months of age, the incidence of sesamoid disease as assessed by radiographic changes in the sesamoid bones was 73 per cent (30 of 41 dogs). Six of the 12 dogs which were lame owing to sesamoid disease got better without specific treatment. It was concluded that sesamoid disease can result in clinical lameness in young rottweilers, but that subclinical disease is common.

Age Factors↗
PubMed1982

Extracutaneous mast-cell tumor in the dog.

Three neoplasms of extracutaneous mast-cell origin, arising from the nasopharynx, oral cavity, and hepatopancreatic lymph nodes respectively, were diagnosed in three dogs. The neoplasms had histologic features similar to those of cutaneous mast-cell tumors, but had limited metastasis mostly involving the regional lymph nodes. One dog had a perforating duodenal ulcer, suggesting that duodenal ulcers can occur with extracutaneous tumors as they do with some cutaneous mast-cell tumors in the dog.

Animals↗