The immunohistology of CD40 in human oral epithelium in health and disease

BACKGROUND: CD40 has a role in the regulation of immune responses, cell proliferation and migration, and apoptosis. Little is known of its distribution in oral mucosal pathology. METHODS: Oral keratinocyte lines were tested for CD40 protein by Western blotting. Immunohistochemistry was used to stain paraffin sections of oral mucosa in health and in inflammatory, reactive, dysplastic and malignant disease. RESULTS: Western blotting confirmed the presence of CD40 in oral keratinocytes. CD40 was generally expressed by keratinocytes in the basal layer, with variable parabasal expression. Langerhans cells also stained positively. Expression was lost in nine of 33 (27%) epithelial dysplasias, seven of which were severe. Eighty-one percent of well, 69% of moderately and 50% of poorly differentiated oral squamous cell carcinomas (OSCC) expressed CD40. Overall, 45 of 65 (69%) OSCC were positive. The pattern of expression was unrelated to tumour differentiation. CONCLUSION: CD40 expression by basal and parabasal oral keratinocytes is physiological. Expression is lost in approximately one-third of oral epithelial dysplasias and OSCC. The significance of such loss remains unknown, but may be related to immunological or other abnormalities of keratinocyte homeostasis.     

Amyloidaceous ulcerated gingival hyperplasia: a newly described entity related to ligneous conjunctivitis

Gingival hyperplasia may be genetic, may be acquired as a consequence of exposure to drugs and other agents or may appear as part of a more widespread disorder. Five patients who acquired gingival hyperplasia due to amyloidaceous deposits staining only for fibrin are presented. This appears to be a new entity related to ligneous conjunctivitis.     

Photodynamic therapy of normal rat arteries after photosensitisation using disulphonated aluminium phthalocyanine and 5-aminolaevulinic acid.

Photodynamic therapy of cancer exposes adjacent arteries to the risk of injury and the possibility of haemorrhage and thrombosis. The nature of photodynamic injury to normal arteries has not been satisfactorily defined, and the ability of arteries to recover with time is unclear. To clarify these issues, we have investigated the effects of PDT on rat femoral arteries, using a second-generation photosensitiser, disulphonated aluminium phthalocyanine, and a new method of photosensitisation, using endogenous synthesis of protoporphyrin IX following systemic administration of 5-aminolaevulinic acid (ALA). Pharmacokinetic studies of sensitiser fluorescence were carried out to determine peak levels of sensitiser. Subsequently photodynamic therapy at times corresponding to maximal fluorescence was performed using two light doses, 100 and 250 J cm-2. The nature of injury sustained and recovery over a 6 month period was investigated. Three days following PDT, all vessels treated showed complete loss of endothelium, with death of all medial smooth muscle cells, leaving an acellular flaccid artery wall. No vascular occlusion, haemorrhage or thrombosis was found. A striking feature was the lack of inflammatory response in the vessel wall at any time studied. Re-endothelialisation occurred in all vessels by 2 weeks. The phthalocyanine group showed repopulation of the media with smooth muscle cells to be almost complete by 3 months. However, the ALA group failed to redevelop a muscular wall and remained dilated at 6 months. Luminal cross-sectional area of the ALA-treated group was significantly greater than both control and phthalocyanine groups at 6 months. All vessels remained patent. This study indicates that arteries exposed to PDT are not at risk of catastrophic haemorrhage or occlusion, a finding that is of significance for both the local treatment of tumours and the use of PDT as an intraoperative adjunct to surgery for the ablation of microscopic residual malignant disease.     

How has psycho-behavioural research advanced our understanding of hypoglycaemia in type 1 diabetes?

Almost 100 years since the discovery of insulin, hypoglycaemia remains a barrier for people with type 1 diabetes to achieve and maintain blood glucose at levels which prevent long-term diabetes-related complications. Although hypoglycaemia is primarily attributable to the limitations of current treatment and defective hormonal counter-regulation in type 1 diabetes, the central role of psycho-behavioural factors in preventing, recognizing and treating hypoglycaemia has been acknowledged since the early 1980s. Over the past 25 years, as documented in the present review, there has been a substantial increase in psycho-behavioural research focused on understanding the experience and impact of hypoglycaemia. The significant contributions have been in understanding the impact of hypoglycaemia on a person's emotional well-being and aspects of life (e.g. sleep, driving, work/social life), identifying modifiable psychological and behavioural risk factors, as well as in developing psycho-behavioural interventions to prevent and better manage (severe) hypoglycaemia. The impact of hypoglycaemia on family members has also been confirmed. Structured diabetes education programmes and psycho-behavioural interventions with a focus on hypoglycaemia have both been shown to be effective in addressing problematic hypoglycaemia. However, the findings have also revealed the complexity of the problem and the need for a personalized approach, taking into account the individual's knowledge of, and emotional/behavioural reactions to hypoglycaemia. Evidence is emerging that people with persistent and recurrent severe hypoglycaemia, characterized by deeply entrenched cognitions and lack of concern around hypoglycaemia, can benefit from tailored cognitive behavioural therapy.