In mammals, the cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) are a supergene family comprised of four multigene families, named alpha, mu, pi and theta. In man, within the mu class gene family there is a gene (the GSTmu 1 locus) that is polymorphic and is only expressed in 50-55% of individuals. It has previously been reported, using trans-stilbene oxide (tSBO) as a specific substrate for the expressed phenotype, that smokers with the null phenotype had a greater susceptibility to lung cancer. In a subsequent study, it was shown that on Southern blot analyses of human DNAs using a GSTmu 1 cDNA probe a DNA fragment was absent in certain individuals. The absence of this band correlated with the tSBO null phenotype. In the present work, DNA clones derived from GST mu class genomic sequences were used as probes in Southern blot analyses and confirmed the correlation between the lack of a DNA fragment and the null phenotype; moreover in this case, using radioimmunoassay for the GST mu protein, these probes were then used in a genotyping assay to investigate further the association of GSTmu 1 polymorphism with susceptibility to lung cancer. It was found that in a control group of 225 individuals, of unknown smoking history, 42% lacked the restriction fragment and were homozygous null, and therefore 58% were either heterozygous or were homozygous normal. Among 228 lung cancer patients, which included all tumour types, a similar distribution occurred, namely 43% were homozygous and 57% were heterozygous or homozygous normal. If, however, the tumours were analysed by tumour type a small but significant positive correlation with the homozygous null genotype was seen in squamous carcinoma of the lung, and an apparently negative correlation with adenocarcinoma of the lung.

Background-Bronchiectasis is a chronic suppurative lung disease characterised by irreversible dilation of the bronchi and persistent purulent sputum. The immunopathology of the disease was studied using a quantitative immunostaining technique with particular reference to T lymphocytes, macrophages, and granulocytes. (Thorax 1998;53:685-691) Methods-Bronchial

C-reactive protein (CRP) has been shown to be a useful and sensitive indicator of pyogenic infections in many clinical situations, including acute pneumonia and infective pulmonary exacerbations in cystic fibrosis patients. Exacerbations of COPD are often, but not always, associated with demonstrable infection. The value of CRP measurement in this situation has not been assessed. We have evaluated CRP measurement in 50 patients [age 71 +/- 8 (SD) years] who were admitted to hospital with clinical evidence of exacerbation [PaO2 = 7.3 +/- 1.3 (SD) kPa, baseline FEV1 = 0.8 +/- 0.4 (SD) l]. These patients all had serial measurement of CRP [polarizing immunofluorescence (Abbot, TDx)], peripheral white cell count (WCC), body temperature, peak expiratory flow rate, Karnofsky performance status and chest X-ray, in addition to serial sputum bacteriological analysis carried out in a specialized laboratory. CRP was elevated (> 10 mg l-1) in all patients (n = 29) with proven infection [103 +/- 98 (SD) mg l-1]. Levels were markedly elevated in patients infected with Streptococcus pneumoniae (mean 156 mg l-1); there was also a rapid fall in the CRP with therapy. WCC fell with therapy, giving a correlation with CRP level (r = 0.44, P < 0.01). Since CRP elevation was observed in patients having exacerbation with proven infections and also in those where infection was not proven, it is possible that, while it is a marker for COPD exacerbation, it is not necessarily a marker of bacterial infection per se. However, it is evident from our study that it is of value in the assessment of exacerbations of COPD, where routine bacterial culture of sputum is often unreliable, and thus the measurement of serum CRP may provide an additional objective indicator of infection.

No abstract