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Biomedical subjects

G E Orchard

Publications and source records attributed to G E Orchard.

14 recordsLinked to original sources
PubMed2001

Effects of solar-simulated radiation dose fractionation on CD1a+ Langerhans cells and CD11b+ macrophages in human skin.

BACKGROUND: There are few human studies investigating the immunosuppressive effects of exposure to solar-simulated radiation (SSR) and its relationship with sunburn/erythema, and few comparative data on the importance of SSR exposure regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end-point for assessing damage to antigen-presenting cells (APCs) in human skin. METHODS: We compared the relationship between SSR-induced erythema and alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema doses (MED). We also investigated whether SSR exposure leads to an accumulation or accommodation of the same end-points by comparing the effects of a relatively low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75 MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose-dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis showed a dose-dependent increase in cell size and altered morphology. Significant depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers. In contrast, dose fractionation protected against alterations in CD1a+ LC morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator of alterations in epidermal APCs and that dose fractionation is an important parameter in the immunological effects of ultraviolet radiation.

Adult↗
PubMed2000

Comparison of immunohistochemical labelling of melanocyte differentiation antibodies melan-A, tyrosinase and HMB 45 with NKIC3 and S100 protein in the evaluation of benign naevi and malignant melanoma.

A panel of three melanocyte differentiation antibodies has been compared with anti-S100 protein and NKIC3 in an assessment of benign and malignant melanocytic lesions. Anti-polyclonal S100 protein labelled all cases of primary cutaneous malignant melanoma, metastatic melanoma, desmoplastic melanoma and myxoid melanomas. In addition all benign and dysplastic naevi were positive. Conversely, HMB 45 was the least sensitive marker, labelling 24/31 primary cutaneous melanomas, 14/24 metastatic melanomas and only 1/6 desmoplastic melanomas. In the case of naevi, only junctional forms labelled consistently. Results for anti-melan-A and anti-tyrosinase were similar, although anti-tyrosinase proved slightly more sensitive in cases of malignant melanoma. NKIC3 revealed similar results to anti-tyrosinase, but had the disadvantage of reduced selectivity. It is concluded that anti-tyrosinase and anti-melan-A are useful additions to the panel of melanocytic monoclonal antibodies. In addition, both antibodies appear to have greater sensitivity for malignant melanoma than the conventionally used HMB 45 and could be considered as supportive markers to polyclonal anti-S100 protein in the diagnosis of malignant melanoma.

Antibodies, Monoclonal↗
PubMed1999

Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: comparison of patients with and without anti-FcepsilonRI or anti-IgE autoantibodies.

BACKGROUND: Previous studies defining the histopathologic features of patients with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain duration and before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: We sought to determine the timing of the inflammatory infiltrate in the wheals of patients with CIU and to detect differences between patients with and without autoantibodies. METHODS: Immunohistochemistry was used to identify neutrophils (neutrophil elastase), T lymphocytes (CD3), and activated eosinophils (EG2) in biopsy specimens from uninvolved skin and wheals present for less than 4 hours and greater than 12 hours in 22 patients with CIU, as well as in biopsy specimens from the skin of 12 healthy control subjects. Patients were identified as having functional autoantibodies on the basis of their serum-evoked histamine release in vitro from the basophils of 2 healthy donors. RESULTS: EG2(+), neutrophil elastase+, and, to a lesser extent, CD3(+) cells were found in greater numbers in wheals undergoing biopsy at less than 4 and greater than 12 hours than in uninvolved skin (P <.05). Patients without autoantibodies (n = 12) had significantly more EG2(+) cells in wheals of greater than 12 hours' duration than patients with autoantibodies (n = 10; P =.02). There was no other difference between patients with and without autoantibodies in the cutaneous cellular infiltrate. CONCLUSION: Neutrophil and eosinophil accumulation occurs early in the evolution of a wheal in patients with CIU, but eosinophil activation may occur later or be more persistent in patients without autoantibodies.

Adult↗
PubMed1999

Malignant melanoma: death by image and ignorance, diagnosis by surgical excision and laboratory investigation.

Malignant melanoma is now one of the most common cancers in the western world. Across Europe, the rise in annual incidence is 4-7%. The criteria for clinical and histological diagnosis are well established; however, an elaborate range of laboratory investigations can provide valuable supplementary information in difficult cases. In this essay, we highlight the incidence and impact of malignant melanoma worldwide, and outline the range of laboratory investigations that can be performed and are so vital in the diagnosis of problematic cases.

Biomarkers, Tumor↗
PubMed1999

Heavily pigmented melanocytic neoplasms: comparison of two melanin-bleaching techniques and subsequent immunohistochemical staining.

The effect of melanin bleaching using permanganate/oxalate and dilute hydrogen peroxide on subsequent immunohistochemical staining of heavily pigmented melanocytic neoplasms is investigated. Permanganate/oxalate precluded the use of some antibodies but allowed much faster bleaching times, whereas dilute hydrogen peroxide enabled a full range of antibodies to be used, yet bleaching times were far longer. Each technique has advantages; however, the choice of method should be determined by the nature of the information needed to make a diagnosis and the speed at which a report is required.

Histocytological Preparation Techniques↗
PubMed1998

The effect of melanin bleaching on immunohistochemical staining in heavily pigmented melanocytic neoplasms.

The accumulation of excessive amounts of melanin in melanocytic lesions can obscure cellular morphology and can further hinder immunocytochemical procedures. We have used a modification of the potassium permanganate/oxalic acid melanin-bleaching technique, involving much reduced bleaching times, in order to remove melanin granules prior to incubation with primary antibody. We have assessed a panel of antibodies applicable to the evaluation of melanocytic lesions and in addition have also assessed antibodies that may be more useful in research. The study attempts to determine which antigens may be affected by bleaching and which are not. Antigens S100, HMB 45, NKIC3, CD34, and L26 are relatively unaffected by this procedure. Factor-VIII-related antigen and vimentin and CD68 antigens produced enhanced staining. In contrast, antigens CD3, CD31, and CD45RO were abolished. In addition, smooth muscle actin and desmin antigens demonstrated considerable nonspecific background staining and were not reliable in this study. This technique demonstrates that a fairly wide range of antigens are preserved after bleaching and that distinction between melanocytes and melanophages can reliably be performed using the conventional immunocytochemical chromogen 3,3-diaminobenzidine and without the need for elaborate counterstaining.

Actins↗
PubMed1997

Cutaneous histopathology of Sézary syndrome: a study of 41 cases with a proven circulating T-cell clone.

Sezary syndrome is an uncommon variant of cutaneous T-cell lymphoma (CTCL) characterized by erythroderma, pruritus, adenopathy, and circulating atypical T-lymphocytes with cerebriform nuclei. The definition of Sezary syndrome can be further refined by including only patients with a circulating peripheral blood population of clonal T-cells. We have evaluated 79 skin biopsies from such a group of 41 erythrodermic patients with circulating Sezary cells and a clonal population of T-cells detected by T-cell receptor-beta gene rearrangement on Southern analysis of peripheral blood mononuclear cells. Histopathologic features consistent with chronic dermatitis were observed in 26/79 (33%) skin biopsy specimens, emphasizing that a non-specific histologic appearance is common. Evidence of CTCL was lacking in 11/41 patients on biopsy of their erythrodermic skin. The survival of these patients was not significantly different from 30/41 patients in whom skin biopsies revealed changes diagnostic of CTCL, such as a dermal lymphocytic band with atypical lymphocytes (18/79, 23%) or a mycosis fungoides-like infiltrate (30/79, 38%). This study confirms that non-specific cutaneous histopathologic findings are common in Sezary syndrome, even when a circulating T-cell clone is present. This stresses the need for peripheral blood genetic analysis and for multiple or repeat skin biopsies in erythrodermic patients when there is high clinical suspicion of CTCL.

Aged↗
PubMed1996

An immunocytochemical assessment of 19 cases of cutaneous angiosarcoma.

Four endothelial cell markers, two selective cytokeratin markers and a monoclonal smooth muscle antibody (SMA) were employed in the assessment of 19 cases of cutaneous angiosarcoma classified according to their degree of tumour differentiation. No labelling was seen for SMA or with cytokeratin markers MNF116 and CBL170. Expression of factor VIII-related antigen was seen in two tumours and positivity for CD34 (QBend 10 antibody) was found in four tumours. By contrast the pan-endothelial cell marker Ulex europeaus agglutinin 1 (UEA-1) and the CD31 marker JC70A labelled all cases of cutaneous angiosarcoma with the exception of one poorly differentiated tumour. These data confirm the endothelial cell origin of angiosarcoma, they demonstrate that CD31 and UEA1 are reliable markers in routinely processed tissue, and they suggest a lymphatic derivation for the tumour. This finding is in marked contrast to Kaposi's sarcoma where CD34 is the most reliable marker.

Antibodies, Monoclonal↗
PubMed1996

Lymphomatoid papulosis: a low-grade T-cell lymphoma?

Lymphomatoid papulosis is a chronic cutaneous lymphoid disease characterised clinically by the presence of recurrent papulonodular or plaque like lesions, which appear benign. Paradoxically, histological and cytopathological features demonstrate features of malignancy. This annotation highlight the current theories and technical advances into the assessment of this condition, with emphasis on possible pathogenic disease mechanisms.

Biomarkers, Tumor↗
PubMed1994

Verruciform xanthoma: an immunocytochemical study.

Verruciform xanthoma is a rare lesion that occurs predominantly on the oral mucosae, but also on other mucosal sites and on the skin. We report an immunocytochemical analysis of the xanthoma cells in three cases of verruciform xanthoma (two vulval and one scrotal), and also attempt to identify human papilloma virus (HPV) as a possible trigger for the production of these lesions. We employed a panel of seven histiocytic markers (CD68 [KP1], KiM1P, HAM 56, lysozyme, vimentin, peanut agglutinin and factor X111a) and two others to identify HPV involvement (CAMVIR-1 and bovine papilloma virus-1 [BPV-1]). Results showed the xanthoma cells to be positive for CD68, KiM1P, HAM 56 and vimentin, with less consistent labelling for peanut agglutinin and lysozyme. CAMVIR-1 and BPV-1 were negative in all three cases. These findings support the view that the xanthoma cells are derived from a monocyte macrophage lineage and fail to demonstrate HPV as the cause.

Adolescent↗
PubMedDate not supplied

Irritant threshold and histological response of epidermis to irritant application.

Individuals vary in their ability to react to irritants, which can be demonstrated for sodium lauryl sulfate (SLS) using the irritant threshold (IT) test. We aimed to study whether the histological and immunohistochemical features of the skin following SLS exposure varied with subject's IT. 8 subjects were recruited. Their IT was measured. Biopsies were taken after 2 hr and 4 hr of occlusion with 20% SLS and control. The specimens were stained with haematoxylin and eosin and for Langerhans cells. At 4-hr, low-threshold subjects developed changes to a greater extent than high-threshold subjects. The relationship of histological reaction to IT could be related to a differential pro-inflammatory cytokine response in subjects. Low IT has been previously associated with a tumour necrosis factor alpha promoter region polymorphism.

Antigens, CD1↗