Devil Facial Tumor Disease.

Devil facial tumor disease (DFTD) is an emergent transmissible cancer exclusive to Tasmanian devils (Sarcophilus harrisii) and threatening the species with extinction in the wild. Research on DFTD began 10 years ago, when nothing was known about the tumor and little about the devils. The depth of knowledge gained since then is impressive, with research having addressed significant aspects of the disease and the devils' responses to it. These include the cause and pathogenesis of DFTD, the immune response of the devils and the immune evasion mechanisms of the tumor, the transmission patterns of DFTD, and the impacts of DFTD on the ecosystem. This review aims to collate this information and put it into the context of conservation strategies designed to mitigate the impacts of DFTD on the devil and the Tasmanian ecosystem.

Humanized anti-CD4 monoclonal antibody therapy of autoimmune and inflammatory disease.

We have investigated the biological and therapeutic properties of a humanized anti-CD4 MoAb, hIgG1-CD4, in patients with refractory psoriasis and rheumatoid arthritis (RA). hIgG1-CD4 is a modulating, non-depleting MoAb, which induced a first-dose reaction in most patients treated. It provided brief symptomatic relief in both conditions, and psoriasis appeared easier to control with conventional agents after MoAb therapy. At the doses used, hIgG1-CD4 did not synergize therapeutically with the panlymphocyte MoAb CAMPATH-1H (C1H) in patients with RA treated sequentially with both agents. There were no serious adverse effects definitely attributable to therapy. Our results are compared with those of other CD4 MoAb studies, and factors influencing the outcome of therapy are discussed.

Treatment of extramammary Paget's disease by radiotherapy.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, which usually occurs in the elderly. Wide local excision is the recommended treatment, although this may not always be feasible. We report our experience of EMPD treated by radiotherapy in five patients. The radiotherapy was well tolerated in each case, and there were no signs of recurrence during follow-up (6 months-8 years). This study shows that radiotherapy is a useful alternative therapy for EMPD, and should be considered particularly in elderly patients who may not tolerate surgery.

Mid-dermal elastolysis.

We report a case of mid-dermal elastolysis in which dermal inflammation was a mild but definite feature. The aetiology of this condition remains unknown, although inflammatory destruction of elastic fibres appears to be the final result. In this study, areas of inflammation exhibited features of a specific immune response, with induction of a number of immune accessory molecules.

Auricular embryonal rhabdomyosarcoma.

Rhabdomyosarcoma is an uncommon tumour that may present at a wide variety of different sites. We report a 4-year-old girl who developed an embryonal rhabdomyosarcoma arising in the left pinna which was clinically indistinguishable from a lymphangioma. The case illustrates that this neoplasm can be easily misdiagnosed because of its variable morphology. Early recognition is important as successful treatment is now possible with a combination of chemotherapy, surgery and/or radiotherapy.

Scleroderma and the carcinoid syndrome.

The follow up of a case of the carcinoid syndrome complicated by scleroderma is reported, in which progress of the disease may have been halted by treatment with a combination of cyproheptadine, parachlorophenylalanine and prednisolone. Impairment of tryptophan and 5-hydroxytryptamine (serotonin) metabolism appears central to the development of skin fibrosis in the carcinoid syndrome and may be indicative of important mechanisms in the pathogenesis of idiopathic scleroderma.

Recognition of two distinct major antigens by bullous pemphigoid sera.

Sera from 17 patients with bullous pemphigoid identified a range of polypeptides of relative molecular mass (Mr) 240,000, 230,000, 190,000, 180,000, 120,000 and 100,000 from extracts of SCaBER cells, cultured human keratinocytes or human epidermis, using an immunoblotting technique. The pattern of polypeptides was characteristic for the patient serum and individual sera identified similar polypeptides from all three substrates. All 17 sera recognized major polypeptides of either Mr 230,000 (11 sera) or Mr 180,000 (seven sera) under the denaturing conditions used for immunoblotting studies. Sera from 12 patients were also examined using an immunoprecipitation technique. Polypeptide(s) of Mr 230,000 were immunoprecipitated from extracts of SCaBER cells by 11 of these sera, despite immunoblotting patterns of Mr 180,000 (or less) for three of the 11 sera. None of the minor polypeptides recognized in immunoblotting studies were immunoprecipitated by these sera. Localization of antigens was determined by binding of sera to intact or permeabilized SCaBER cells in an ELISA. Sera which recognized the Mr 230,000 polypeptide under denaturing conditions also identified an intracellular epitope in SCaBER cells, while sera which identified the denatured Mr 180,000 polypeptide bound to a cell surface epitope. Two distinct major antigens are recognized by bullous pemphigoid sera. These both appear as molecules of Mr 230,000 under non-denaturing conditions, but only one of the molecules is dissociated to produce a Mr 180,000 polypeptide under denaturing conditions. Epitopes on these two major antigens are localized on either side of the cell membrane.

Keratinocyte culture.

The in vitro growth of keratinocytes has proved to be an important tool in the study of the normal biology and disease processes involving the skin, e.g., the influence of extrinsic regulators of growth and differentiation, effects of pharmacological agents, dermo-epidermal interactions, tissue antigenicity, and models of carcinogenesis.

Binding of bullous pemphigoid and pemphigus vulgaris sera to SCaBER cell line in an ELISA.

Specific antibodies present in the sera of patients with bullous pemphigoid or pemphigus vulgaris were detected in an enzyme-linked immunosorbent assay (ELISA) employing a squamous carcinoma cell line, SCaBER, as substrate. Bullous pemphigoid sera bound preferentially to permeabilized cells, suggesting that the antigens are largely intracellular. The assay may prove to be a useful addition to current methods of detecting circulating antibodies in these patients.

Cultured keratinocytes as biological wound dressings.

Human epidermal keratinocytes now can be grown reliably and reproducibly in vitro to form multilayered epithelium. These sheets of cultured keratinocytes have been used successfully to autograft patients with severe burns, leg ulcers and following excision of extensive congenital naevi. Whilst the technique carries the obvious advantage of huge expansion of the initial skin biopsy, thus removing the need for painful and slow healing donor sites, problems have been encountered. The take rate has been lower than with conventional split skin grafts. The take rate can be increased by the provision of a dermis. This may be achieved by providing an allodermis or by the use of a highly meshed autologous split skin graft. The wound is then covered with autologous cultured keratinocyte grafts. Manufactured dermis has been under investigation for some years and animal work suggests this may be an alternative approach. There is a delay of 2 to 3 weeks for culture of the autologous sheets of keratinocytes. This has led to the use of allogeneic grafts in a number of patients. The long term survival of these grafts has been attributed to the loss of antigen presenting cells during tissue culture. However some grafts have been rejected. Studies currently in progress may help resolve these anomalies. Whilst a number of problems remain to be solved the technique of cultured keratinocyte grafting takes wound care into an exciting new era. Skin banks may now become more than a surgeon's dream.

Micaceous and keratotic pseudoepitheliomatous balanitis and rapidly fatal fibrosarcoma of the penis occurring in the same patient.

A 55-year-old man had a rare, benign condition of the penis, micaceous and keratotic pseudoepitheliomatous balanitis, for 9 years before developing an aggressive soft tissue sarcoma of the glans. Five months after the appearance of this tumour, the patient died with widespread metastases. The sarcoma was small and superficial and the limited recorded experience suggested that local excision should offer a good prognosis. However, the histology showed poor differentiation and it would seem that this may be the important factor in the management and prognosis of penile sarcoma, as it is in sarcoma at other sites.