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Biomedical subjects

M J Tidman

Publications and source records attributed to M J Tidman.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

Lamellar bodies in hyperkeratosis lenticularis perstans.

An ultrastructural study of lesional skin from 4 subjects with hyperkeratosis lenticularis perstans (Flegel's disease) demonstrated variable numbers of lamellar bodies of normal size and architecture within cells of the stratum granulosum and the upper stratum spinosum. Their characteristic lamellate inclusions were frequently observed within the intercellular spaces. These observations suggest that the lamellar bodies are qualitatively normal in Flegel's disease.

Adult↗

Hemidesmosome heterogeneity in junctional epidermolysis bullosa revealed by morphometric analysis.

In order to examine the claim for a numerical and structural abnormality of the hemidesmosomes in junctional epidermolysis bullosa (JEB), a morphometric analysis of unseparated dermal-epidermal junction was undertaken in 11 subjects with JEB. Of these, 5 died in infancy with "lethal" disease, 3 were children still alive at 1-6 years with "indeterminate" disease, and 3 were females aged 20-60 years with variable phenotypic expression of "nonlethal" JEB. All the lethal cases had reduced numbers of hemidesmosomes which were small and lacked normal subbasal dense plates, with the exception of 1 patient whose hemidesmosomes were structurally and numerically normal. The principal hemidesmosome abnormality in the 3 cases with indeterminate JEB was the absence of normal subbasal dense plates. In 2 of the 3 cases of nonlethal JEB, the hemidesmosomes appeared normal, whereas in the third patient they showed a similar abnormality to that present in the majority of the lethal group. These results demonstrate that JEB is an ultrastructurally heterogeneous condition, and suggest that, even though the hemidesmosome abnormalities may be of diagnostic value, they do not correlate sufficiently well with the clinical outcome to be useful as a prognostic indicator.

Adult↗

Structural and functional properties of the dermoepidermal junction in obligate heterozygotes for recessive forms of epidermolysis bullosa.

To determine whether heterozygotes for the severe recessive forms of epidermolysis bullosa (EB) partially express characteristic structural or functional abnormalities of the dermoepidermal junction, and thereby allow detection of the carrier state, a controlled morphometric analysis of the junction and the measurement of suction blister times were undertaken in obligate heterozygotes for junctional EB and generalized-recessive dystrophic EB. Skin from generalized recessive dystrophic EB carriers had significantly reduced numbers of anchoring fibrils, and suction blisters showed a tendency to form more rapidly in junctional EB carriers. However, neither of these abnormalities is sufficiently large or consistent to enable the reliable identification of the respective heterozygote state.

Adolescent↗

Evaluation of anchoring fibrils and other components of the dermal-epidermal junction in dystrophic epidermolysis bullosa by a quantitative ultrastructural technique.

To examine the possibility that differences in the structure and population density of anchoring fibrils (AF) and other components of the dermal-epidermal junction might distinguish between genetically and clinically distinct varieties of dystrophic epidermolysis bullosa (DEB), a controlled ultrastructural morphometric study of nonseparated keratinocyte-associated dermal-epidermal junction was undertaken in a total of 17 patients with DEB. Seven patients had dominant DEB, 3 had localized recessive DEB, and 7 had severe, generalized recessive DEB. Nonlesional, unscarred skin was obtained from standard body regions. Criteria for the identification of AF were a mandatory union with the lamina densa and the presence of central banding and/or fanning of the extremities. No AF were detected in 9 technically suitable samples from patients with severe recessive DEB. Structurally normal AF were present, but significantly reduced in number, in both dominant and localized recessive DEB, compared with site-matched samples from 12 healthy adults. There was no difference in AF characteristics between dominant and localized recessive DEB, or between sites of predilection and nonpredilection for blisters. The presence or absence of albopapuloid lesions in dominant DEB did not influence AF counts. There was no difference in numbers of hemidesmosomes, basal cell plasmalemmal vesicles, or dermal microfibril bundles in any group of DEB patients compared with controls. Thus, although severe mutilating DEB can be distinguished by routine transmission electron microscopy, the dominant and localized recessive forms cannot be differentiated on the basis of AF structure or numbers.

Adult↗

A study of the dermo-epidermal junction in dystrophic epidermolysis bullosa using the periodic acid-thiosemicarbazide-silver proteinate technique.

Dermo-epidermal separation in dystrophic epidermolysis bullosa (DEB) is thought to results from an abnormality of anchoring fibrils which, in normal skin, are stained selectively by the periodic acid-thiosemicarbazide-silver proteinate technique. This method was applied to non-lesional skin from four patients with generalized recessive DEB, five with localized recessive DEB and one with dominant DEB. No anchoring fibrils were present in the subjects with generalized recessive DEB, but they were morphologically normal in the case of dominant DEB and in three patients with mild localized recessive DEB. Two patients with a more severe form of localized recessive DEB possessed attenuated anchoring fibrils which lacked the normal banding of the mid-portion. The lamina densa, normally unlabelled, was consistently stained in patients with generalized recessive DEB, suggesting a biochemical abnormality of this structure.

Adolescent↗

Ultrastructural morphometry of normal human dermal-epidermal junction. The influence of age, sex, and body region on laminar and nonlaminar components.

To obtain baseline data for future studies on such processes as wound healing, carcinogenesis, and blistering, a morphometric analysis of the dermal-epidermal junction was undertaken on normal skin from 3 or 4 standard sites on the arm and leg of 12 subjects aged 20-60 years. Lamina densa was thinner in females than in males (p less than 0.01) but no sex difference was apparent for lamina lucida. Both laminar elements were thinner beneath melanocytes than beneath keratinocytes. Sex, age, and body region had no apparent influence on numbers of hemidesmosomes or basal cell plasmalemmal vesicles, nor was there a significant variation of these structures among individuals. Numbers of dermal microfibril bundles diminished with age (p less than 0.01). Anchoring fibril counts varied widely both among individuals (p less than 0.025) and within the same subject; there were fewer in the upper arm compared with different parts of the leg (p less than 0.005). These results emphasize the importance of appropriate controls in studies of physiologic and pathologic conditions involving the dermal-epidermal junction.

Adult↗