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Biomedical subjects

D M MacDonald

Publications and source records attributed to D M MacDonald.

At least 91 records · Page 5Linked to original sources
PubMed1988

Products of class II major histocompatibility complex gene subregions are differentially expressed on keratinocytes in cutaneous diseases.

Aberrant expression of class II major histocompatibility complex (MHC) subregion antigens by keratinocytes was examined immunohistochemically in a range of cutaneous disorders. Although cell surface expression of human lymphocyte antigen (HLA)-DR was observed, HLA-DQ and HLA-DP were not expressed in any disorder investigated except for allergic contact dermatitis. Epidermal Langerhans cells expressed antigens of all three subregions on the cell surface. Differential expression of class II MHC subregion antigens may be related to tissue levels of gamma-interferon or to different functions of each subregion.

Adult↗
PubMed1988

Routine diagnostic immunohistochemical labeling of extracellular antigens in formol saline solution-fixed, paraffin-embedded cutaneous tissue.

A technique involving modification of the routine paraffin embedding procedure that allows immunohistochemical examination of extracellular antigens by light microscopy is described. The method is thus suitable for routine diagnostic immunofluorescence studies, permitting reliable, reproducible immunolabeling of immunoglobulins and complement components usually not preserved by routine processing procedures. Immunoreactivity as measured by direct immunofluorescence and immunoenzymatic (peroxidase-antiperoxidase) histochemistry is comparable to results with fresh-frozen cryostat sections. Morphologic preservation is superior, however, and the processed material is suitable for routine hematoxylin-eosin staining.

Antigens, Surface↗
PubMed1988

Surface-bound immunoglobulin E on antigen-presenting cells in cutaneous tissue of atopic dermatitis.

Both type I and type IV hypersensitivity reactions have been implicated in the pathogenesis of atopic dermatitis. Using monoclonal antibodies we have identified IgE on the surface of cutaneous dendritic cells in both lesional and nonlesional skin. Double immunofluorescence labeling demonstrates these cells to be antigen-presenting cells. Immunoglobulin E (IgE) was not identified on such cells either in atopic individuals with no history of dermatitis or in patients with a range of other dermatoses. Further studies are consistent with IgE being bound to the cell surface via an Fc-IgE receptor. We conclude that this finding is specific for atopic dermatitis and thus may provide a link between the two types of hypersensitivity reactions frequently observed.

Adolescent↗
PubMed1988

Localization of cutaneous antigens by the immunogold-silver staining technique.

Immunogold-silver staining (IGSS) was evaluated for the localization of cutaneous antigens in frozen and paraffin-embedded tissue, employing antibodies to a variety of intracellular, cell-surface and extracellular epitopes in an indirect immunogold reaction, followed by silver enhancement. The principal advantages of IGSS are the avoidance of toxic reagents and the production of a silver precipitate that is permanent, clearly visible and of sufficient contrast with the reaction products of alternative immunolocalizing techniques to be of value in double-labelling procedures. It seems to localize antigenic determinants well, but does not appear to be particularly sensitive, especially for the demonstration of antibodies to extracellular constituents. Limitations of IGSS include the propensity to non-specific staining, and the need to vary the duration of the development stage during silver enhancement.

Antigens↗
PubMed1988

Gamma-interferon induced human keratinocyte HLA-DR synthesis: the role of dermal activated T lymphocytes.

Experiments were performed to examine the hypothesis that the surface expression of HLA-DR by keratinocytes in certain disease states is conferred by the activity of gamma-interferon, derived from dermal activated T lymphocytes. In vivo studies revealed a spatial relationship between keratinocyte HLA-DR expression and activated T lymphocytes within the dermal inflammatory infiltrate. In vitro studies confirmed that gamma-interferon can induce keratinocyte synthesis of HLA-DR. These results suggest that, in vivo, gamma-interferon produced by activated T lymphocytes induces keratinocyte HLA-DR synthesis and expression.

Adult↗
PubMed1988

Distinctive epidermal atypia in immunosuppression-associated cutaneous malignancy.

The histopathological appearance of proliferative squamous lesions removed from the skin of iatrogenically immunosuppressed patients differs subtly from that of classical malignant and premalignant epidermal lesions. The majority of cases show 'Bowenoid' changes with a marked degree of cellular atypia including characteristic multinucleate cells.

Adult↗
PubMed1988

Keratin expression in epidermolysis bullosa simplex (Dowling-Meara).

The Dowling-Meara variant of epidermolysis bullosa simplex (EBS) is characterized microscopically by clumping of the keratin tonofilaments within areas of incipient blistering, thereby raising the possibility that an abnormality of the keratin cytoskeleton might underlie blister formation in this condition. In order to investigate keratin expression in Dowling-Meara EBS, the staining profile of a panel of antikeratin monoclonal antibodies was examined in perilesional skin from 5 affected subjects, using a standard immunoperoxidase technique. Normal labelling characteristics were demonstrated by antibodies identifying keratins of the basal and suprabasal compartments of normal interfollicular epidermis and of simple epithelia (keratin 19). In addition, a keratin expressed in hyperproliferative epidermal states was shown to be absent. The results suggest that the profile of keratin synthesis is normal in Dowling-Meara EBS and that the tonofilament clumping may be, therefore, the result of a post synthetic modification of keratin molecules.

Adult↗
PubMed1987

Delayed-onset synergism between leukotriene B4 and prostaglandin E2 in human skin.

The time-course of cutaneous inflammatory responses to LTB4 and PGE2 both alone and in combination has been studied in 10 healthy volunteers. LTB4 induced a transient wheal and flare response in some subjects, maximal at 15 minutes and succeeded by an erythematous, indurated lesion at 2-4 hours. PGE2 elicited a wheal and erythema response which resolved within 1-2 hours. Combination of LTB4 and PGE2 produced acute wheal and erythema responses which did not differ significantly from the summation of responses to the individual constituents of the mixture or from responses to a two-fold increase in the concentration of either component. Wheal and erythema responses persisted, however, with significant potentiation of responses 4 hours after injection. As both leukotrienes and prostaglandins are generated in acute allergic reactions, the effects of these mediators in combination could contribute to persisting and late-onset responses to allergen, in both the skin and lung. In particular, sustained responses to the combination of LTB4 and PGE2 might be important in the pathogenesis of inflammatory skin diseases such as psoriasis.

Adult↗
PubMed1987

Pachyonychia congenita with cutaneous amyloidosis and hyperpigmentation--a distinct variant.

Two kindreds manifesting an unusual form of pachyonychia congenita are described. Clinical involvement consists of nail dystrophy, which tends to improve with age, and moderate palmoplantar hyperkeratosis. In addition, all affected members show a characteristic pattern of cutaneous hyperpigmentation, which resembles macular amyloidosis around the neck and waist, but which confers a dappled appearance to the axillae, popliteal fossae, thighs, buttocks, and lower aspect of the abdomen. With advancing age the pigmentation fades. Histologic and ultrastructural examination of the hyperpigmented skin has revealed pigmentary incontinence and deposition of amyloid within the papillary dermis. These features appear to constitute a distinct variant of pachyonychia congenita.

Adolescent↗
PubMed1987

Epidermal class II human lymphocyte antigen expression in atopic dermatitis: a comparison with experimental allergic contact dermatitis.

Epidermal patterns of class II human lymphocyte antigen (HLA) expression in atopic and allergic contact dermatitis have been compared, using monoclonal antibodies recognizing each subregion. Expression of class II human lymphocyte antigens on keratinocytes has been confirmed in allergic contact dermatitis, while we have found them to be absent in atopic dermatitis. This finding argues that cell-mediated immune responses, possibly to epicutaneous contact with allergen, are not implicated in the pathogenesis of atopic dermatitis.

Adult↗
PubMed1987

A combination of phototherapy and cholestyramine for the relief of pruritus in primary biliary cirrhosis.

A patient with primary biliary cirrhosis is reported in whom UV phototherapy alone was repeatedly effective in controlling severe pruritus. Symptomatic relief was sustained by introducing cholestyramine at a low dosage, despite previous failure of the drug alone to produce any therapeutic benefit, even in large doses. Bile acid concentrations were measured in sera, urine and suction blister fluid from skin exposed to ultraviolet light before, during and following treatment. The findings suggest that phototherapy reduces cutaneous bile acid levels which can subsequently be maintained by low dose cholestyramine. Routine liver function tests remained unaltered. This combination of phototherapy and cholestyramine may be useful in controlling severe pruritus in primary biliary cirrhosis when the drug alone is not tolerated or is ineffective.

Adult↗
PubMed1987

The cellular inflammatory response in nicotinate skin reactions.

Sequential skin biopsies of nicotinate-treated skin from nine normal subjects, three aspirin-pretreated normal subjects and six atopic eczema patients were examined. An erythematous skin reaction was seen in the nine normal subjects and to a lesser degree in one atopic eczema patient, but not in the aspirin-pretreated subjects nor in five remaining atopics. Accumulation of a mononuclear cell perivascular infiltrate was seen from 15 min onwards in the normal subjects. Neutrophils became the predominant cell invading thickened vessel walls and in the perivascular space beginning at 2 h and persisting up to 48 h. Leucocytoclasis was observed at 24 h. Immunofluorescence studies showed only non-specific fibrinogen deposits in papillary capillaries in the three groups of subjects. The chloroacetate esterase reaction and immunohistochemical labelling with OKM I confirmed a marked neutrophilia at 2 h and 24 h. Neutrophils were seen in one atopic eczema patient, but were not observed in the remainder, nor in the skin of the aspirin-pretreated normal subjects. Topical application of nicotinate causes non-allergenic, leucocytoclastic vascular damage in normal skin which can be inhibited by aspirin and which is reduced or absent in atopic eczema.

Adult↗
PubMed1987

A clinicopathological study of Flegel's disease (hyperkeratosis lenticularis perstans).

The clinical and histopathological features of 12 female patients with Flegel's disease were studied. The onset of this dermatosis was delayed until adulthood. The eruption consisted of scaly papules 1-5 mm in diameter which developed principally on the lower legs, upper arms and pinnae. Histopathologically there were discrete foci of hyperkeratosis with some parakeratosis over an attenuated and partially spongiotic epidermis. A genetic influence in this disorder was suggested by its occurrence in sisters in two families and in a mother and daughter. Immunohistochemical and biochemical studies suggested that there is a disorder of keratinocyte proliferation in the disease.

Adolescent↗