Current paradigms of chronic obstructive pulmonary disease (COPD) treatment suggest stratifying patients by their symptoms, utilising three main drug classes, but it is unclear if this approach will substantially alter the progression of the disease in the long term. More treatment options are needed which target the underlying pathology of the condition. Whilst many inflammatory cells are implicated in COPD, the neutrophil is by far the most abundant and has been extensively associated with disease pathogenesis. Neutrophil products are thought to be key mediators of inflammatory changes in the airways of COPD patients, causing pathological features such as emphysema and hypersecretion of mucus. High rates of bacterial colonisation and recurrent infective exacerbations of COPD, as well as evidence of neutrophil-associated host damage suggest that neutrophil functions may be impaired in COPD. This concept is supported by studies demonstrating impaired migratory accuracy and increased degranulation and reactive oxygen species release, with some evidence of altered cellular signalling pathways which might be exploitable as therapeutic targets. This review discusses our evolving understanding of neutrophil function in both health and COPD and highlights the role of this cell in disease pathogenesis, to determine whether this key inflammatory mediator represents a viable therapeutic target to prevent disease progression.

Summary.-Slices of human prostatic adenocarcinoma obtained by transurethral resection were maintained in organ culture for 4 days. Preservation of histological appearance was good with little evidence of necrosis within the viable tissue. Slices of tumour cultured in the presence of testosterone showed a morphological change to a more differentiated type of neoplasm whereas explants cultured in the absence of steroid hormone, or with stilboestrol diphosphate, showed no change. In the case of a relatively anaplastic tumour, testosterone produced a significant increase in the number of mitotic figures seen.

Slices of human benign prostatic hyperplasia were maintained in organ culture in the presence of [3H]-or [14C]testosterone. Explants concentrated radioactivity from the culture medium, although this effect was depressed by the inclusion of foetal calf serum in the medium.Testosterone was metabolised to products with chromatographic mobilities corresponding to androstanediols, androsterone, dehydroepiandrosterone, and androstanedione. The principal metabolite was identified as 5\ g=a\ \ x=r eq-\ dihydrotestosterone, and small amounts of testosterone and androstenedione were also found.As culture time increased from 1 to 6 days there was a diminution in the proportion of 5\g=a\-, and an increase in 17-ketometabolites, indicating a swing to a less physiological pattern of testosterone metabolism by the aging culture. Testosterone metabolism was thought to provide a sensitive index by which to evaluate changes in culture conditions. It has been found possible to maintain human prostatic slices in organ culture so that the morphology of the cultured expiants resembled that of the fresh tissue (McMahon et al. 1972; McMahon Se Thomas 1973). To achieve greater confidence in this experimental model it is desirable to demonstrate similarities ') Present address:

No abstract