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Biomedical subjects

M J Tidman

Publications and source records attributed to M J Tidman.

At least 55 records · Page 3Linked to original sources

Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function.

We have identified mutations in keratins K5 (Arg331Cys) and K14 (Val270Met) in two kinships affected by the dominantly-inherited skin blistering disease, Weber-Cockayne epidermolysis bullosa simplex (EBS-WC). Linkage analysis, DNA sequencing and clinical and ultrastructural analysis are combined to provide the first detailed description of classical EBS-WC. Both phenotypes show similar blistering on trauma, indicating that both mutations compromise the structural resilience of the basal keratinocytes by affecting the keratin cytoskeleton. The location of these mutations in the L12 linker, which bisects the alpha-helical rod region of intermediate filament proteins, identifies another keratin mutation cluster leading to hereditary skin fragility syndromes.

Age of Onset↗

Major histocompatibility class II antigen expression on the surface of epidermal cells from normal and ultraviolet B irradiated subjects.

The influence of ultraviolet B irradiation in therapeutic doses on MHC II-positive epidermal cell numbers and their surface MHC II antigen expression was studied quantitatively using light microscopic immunoperoxidase and immunogold electron microscopic techniques. In multiple ultrathin sections through many MHC II-positive epidermal cells from five healthy subjects, prior to ultraviolet exposure, Langerhans cells and indeterminate cells were found to express similar densities of surface MHC II antigens, which were uniformly distributed over the cell surface. The variation in surface MHC II antigen expression on 97 dendritic epidermal cells from one subject was normally distributed. Following a 6-week course of ultraviolet B irradiation, in the same doses as those normally used for the treatment of psoriasis, MHC II-positive epidermal cell numbers were significantly reduced (mean decrease to 51% of the pre-UVB sample; p < 0.001 analysis of variance), but their surface MHC class II antigen density was significantly increased (p < 0.05 analysis of variance). No MHC II-negative Langerhans cells were detected in either the pre- or post-UVB samples.

Adult↗

Cutaneous leishmaniasis in British troops from Belize.

The medical records of 306 British soldiers in whom a clinical diagnosis of cutaneous leishmaniasis had been made following a tour of duty in Belize were analysed. Parasitological confirmation of the diagnosis was established in 187 cases; leishmania were cultured in 117 cases and Leishman-Donovan bodies were identified histologically in a further 70 cases. Leishmania braziliensis braziliensis was identified in 78 cases and Leishmania mexicana mexicana in a further 29 cases. Seventy-one per cent of patients had a single lesion which, in most cases, occurred on the exposed extremities. The mean diameter of the ulcers was 14.4 mm. Treatment with sodium stibogluconate was effective. Two regimens were used, consisting of either 600-800 mg daily given initially for 10 days, or 600 mg b.d. given initially for 14 days. Of those allocated to the lower dose regimen 48.5% were cured after the initial 10-day course, and ultimately the ulcers of 93% of patients healed following more prolonged treatment at this dose. Of those allocated to the higher dose regimen 63.9% were cured after the initial 14-day course and ultimately the ulcers of all patients healed after more prolonged treatment at this dose. A transient leucopenia and a rise in liver enzymes were noted during treatment, and these changes were dose-dependent. No cases of mucocutaneous leishmaniasis were encountered.

Adult↗

A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.

An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.

Drug Administration Schedule↗

Epidermolysis bullosa acquisita occurring in association with systemic lupus erythematosus.

A 77-year-old retired male physician with a 6-year history of systemic lupus erythematosus (SLE) developed a mechanobullous eruption, the features of which were clinically and immunopathologically consistent with a diagnosis of 'classical' epidermolysis bullosa acquisita (EBA). As EBA shares immunopathological findings with a number of cases reported as the 'bullous eruption of SLE', the clinical findings commonly recognized as 'classical EBA' may, in patients with SLE, represent a specific subset of the bullous eruption of SLE rather than a separate diagnostic entity. There are few reports in the literature describing classical EBA in patients with SLE. Findings in this patient add further support to the suggestion that EBA occurring in association with SLE, represents a subset of the bullous eruption of SLE, the clinical features of which may be modified by genetic susceptibility or disease activity.

Aged↗

Epidermolysis bullosa simplex (Dowling-Meara). A clinicopathological review.

The clinicopathological features of 22 cases of the Dowling-Meara form of epidermolysis bullosa simplex (DM-EBS) (11 males, 11 females; aged 5 days-46 years) were reviewed using data collected over a 10-year period. All cases presented clinically within the first 5 days of life. Early blisters were often large (up to 5 cm in diameter), and were mostly acral and particularly periungual. Some cases presented with more widespread erosive skin changes, and two neonates with extensive skin involvement died as a result of overwhelming sepsis. After the neonatal period a different pattern of blistering occurred with more proximal haemorrhagic, herpetiform clusters of blisters. Central healing with recurrent blistering at the margins of these areas was frequently noted. Other physical signs included varying degrees of intra-oral blistering, nail shedding, nail dystrophy, minor scarring, palmo-plantar keratoderma, a lack of seasonal variation and improvement during later childhood. The underlying pathological mechanism in DM-EBS is basal cell cytolysis, or rarely acantholysis, in association with tonofilament (TF) clumping. TF clumping was found in lesional, perilesional and some non-lesional skin, suggesting that the tonofilament abnormality may be of primary aetiological significance in DM-EBS. TF clumping may be due to specific keratin abnormalities because the altered TF were found in a distribution similar to the known distribution of the basal cell keratins, K5 and K14. The level of blistering was invariably very low within the epidermal basal layer and often less than 0.5 microns above the basement membrane. We conclude that DM-EBS is a distinct, and probably under-recognized genodermatosis which tends to have a good prognosis. However, the disease can occasionally be severe, especially during the neonatal period, when it may be confused with junctional or severe recessive dystrophic EB. Electron microscopy is the best means for demonstrating the characteristics cytoskeletal disorder and confirming the diagnosis.

Adolescent↗

The epidermal basement membrane in basal cell carcinoma: an immunohistochemical study.

An immunohistochemical study of basal cell carcinomas of varying histological type, using a panel of antibodies to constituents of the epidermal basement membrane, showed marked deficiencies in the expression of the antigens identified by the antibodies LH7.2, GB3 and G71. There was no correlation between loss of immunoreactivity to these antibodies and the histological features of the tumour.

Antibodies, Monoclonal↗

The influence of the menstrual cycle and pregnancy on atopic dermatitis.

The prevalence of a premenstrual deterioration in the symptoms of atopic dermatitis, as determined by a postal questionnaire completed by 150 women, was 33%. There was a significant association between a premenstrual worsening of atopic dermatitis and the presence of the symptoms of the premenstrual syndrome (P less than 0.002). Pregnancy had an adverse effect on atopic dermatitis in the majority of cases (52%), usually starting in the first 20 weeks of gestation, although an appreciable proportion of women (24%) had improved during their pregnancy.

Adolescent↗

Malignant hidradenoma--a case report demonstrating insidious histological and clinical progression.

A histologically benign hidradenoma, occurring in a 15-year-old female inadequately excised at first procedure, recurred locally over the course of 11 years and exhibited first local and subsequently regional metastatic spread. The insidious progression was associated with increasing cytological atypia and alteration of epithelial antigenic expression. In view of the rarity of malignant sweat-gland tumours and consequent lack of a specific treatment protocol, this case serves to emphasize the importance of adequate primary local excision, with histological confirmation of clearance, in the management of sweat-gland tumours.

Adenoma, Sweat Gland↗

Scaly lesions.

Explore the source record for details and available documents.

Dermatitis↗

Abnormal expression of G71 antibody at the epidermal basement membrane in basal cell carcinoma.

The antibody G71 is a murine monoclonal antibody directed against an antigen in the basement membrane zone of many human epithelia. Ultrastructurally it is located in the lamina lucida. The epitope is carried on glycoprotein components with molecular weights of 160, 125 and 115 kilodaltons. The authors examined the immunohistochemical expression of G71 antigen, using a standard indirect immunoperoxidase technique, in benign and malignant tumors derived from the epidermis. G71 staining was consistently absent or reduced around basal cell carcinomas (n = 44). In contrast, G71 was present at the basement membrane zone of squamous cell carcinomas (n = 18) and was also frequently expressed within the cytoplasm and on the cell surface of the malignant keratinocytes. The staining pattern of G71 at the basement membrane zone was essentially normal in keratoacanthomas (n = 10), solar keratoses (n = apart from foci of attenuation. In both seborrheic keratoses and intraepidermal squamous 13), seborrheic keratoses (n = 6), and intraepidermal squamous cell carcinomas (n = 8), cell carcinomas cell-surface and cytoplasmic staining were inconstant features. In conclusion, there appears to be a specific defect of G71 antigen expression in basal cell carcinomas.

Antibodies, Monoclonal↗

Abnormal expression of hemidesmosome-like structures by junctional epidermolysis bullosa keratinocytes in vitro.

Hemidesmosomes are frequently rudimentary in junctional epidermolysis bullosa (JEB), and JEB keratinocytes display abnormal attachment to the substrate in culture. Our aim was to determine whether this abnormality reflects defective hemidesmosome synthesis in vitro. Keratinocytes from five JEB patients were cultured under standard conditions. Control cultures, from four healthy males, three patients with dystrophic EB (DEB), and one patient with the simplex variant (EBS), were also examined. Post-confluent cultures were processed for transmission electron microscopy. Hemidesmosome-like structures were counted in electron micrograph montages. The number of hemidesmosome-like structures in JEB cultures (0.97 +/- 0.57, per 10 microns of basal cell membrane) was approximately 17% of the value for normal controls (5.81 +/- 3.08, P less than 0.02). The values for EBS (3.72) and DEB (3.28 +/- 1.44) were not statistically different from normal controls. In addition hemidesmosome-like structures in JEB cultures were morphologically ill-defined, compared with those from controls. This correlated with the loose apposition between JEB keratinocytes and the substrate, which appeared tight in controls. JEB keratinocytes continue to express in vitro a major phenotypic abnormality which characterizes the disease in vivo. Therefore, this model should prove useful in studies determining the pathogenesis and possible new treatments of JEB.

Adolescent↗

Papuloerythroderma--clinical and ultrastructural features.

Papuloerythroderma is a newly described entity. The clinical features of a case and the therapeutic response to systemic corticosteroids are described, together with the immunohistochemical and ultrastructural characteristics of the associated inflammatory infiltrate.

Aged↗

Cutaneous endometriosis: a histopathologic study.

A detailed examination of material from 10 cases of cutaneous endometriosis revealed a range of histopathologic features similar to those found within the uterine endometrium at each of the main phases of the menstrual cycle. However, there appeared to be a poor correlation between histologic appearance and menstrual stage. Recognition of these cyclic variations is important for the accurate diagnosis of cutaneous endometriomas.

Endometriosis↗