Phospholipase C-coupled receptors and activation of TRPC channels.

The canonical transient receptor potential (TRPC) cation channels are mammalian homologs of the photoreceptor channel TRP in Drosophila melanogaster. All seven TRPCs (TRPC1 through TRPC7) can be activated through Gq/11 receptors or receptor tyrosine kinase (RTK) by mechanisms downstream of phospholipase C. The last decade saw a rapidly growing interest in understanding the role of TRPC channels in calcium entry pathways as well as in understanding the signal(s) responsible for TRPC activation. TRPC channels have been proposed to be activated by a variety of signals including store depletion, membrane lipids, and vesicular insertion into the plasma membrane. Here we discuss recent developments in the mode of activation as well as the pharmacological and electrophysiological properties of this important and ubiquitous family of cation channels.

Raised enzyme markers of chronic inflammation in asymptomatic farmers' lung.

Subclinical inflammatory activity may be one of the factors which influences the variable natural history of farmers' lung. Serum lysozyme (LYS) and angiotensin converting enzyme (ACE) have been measured in 52 farmers with a previous history of farmers' lung and in 51 healthy control farmers. The group with farmers' lung assessed during the winter, although having had no recent acute symptoms, had significantly higher levels of LYS and ACE compared to both healthy control farmers seen in winter and farmers' lung subjects seen in summer. There was a mild but significant negative correlation between LYS and farm size in the farmers' lung subjects assessed in winter. The results suggest that active inflammation may be present in subjects with farmers' lung in the absence of acute symptoms during the season when dust exposure occurs as the result of feeding cattle.

Chest symptoms in farming communities with special reference to farmer's lung.

Surveys were carried out on random samples of the farming population in Devon and Wales in order to estimate the prevalence of respiratory symptoms and of positive precipitin reactions to thermophilic fungi. Bronchitis, as defined, was common among the Welsh hill farmers, and the proportion of positive serological tests was higher in both the areas surveyed in Wales as compared with Devon. All three surveys confirmed a previous finding that the proportion of positive precipitin tests was higher among non-smokers than smokers. Although the numbers were small there was some indication that measurement of peak expiratory flow showed different relationships with age in non-smokers according to the presence or absence of positive precipitin tests. The difficulty of determining prevalence rates for farmer's lung is discussed, but the results suggest a rate not dissimilar to those found in two areas of Scotland which were more than 20 times higher than any figure previously reported in Britain.

Farmer's lung in Devon.

Farmer's lung is a cause of disability to agricultural workers in Devon and there is no evidence that the incidence is falling. A survey of known cases was made to assess the degree of disability in relation to the clinical history, the presence of farmer's lung precipitins, tests of lung function, and radiographic changes. Information was obtained about 200 patients diagnosed between 1939 and 1971. A survey of 148 of these patients showed that the disease was most commonly diagnosed in men aged 40 to 50 years and the most important symptom at diagnosis was dyspnoea related to occupational exposure to hay or grain. The onset was often insidious and only 67 patients (45%) were diagnosed during the first year of the disorder. Disability was severe in about one-third of the cases. The degree of disability did not seem to be related to the serological changes recorded either at diagnosis or at the time of our survey. Disability was commonly associated with restriction and reduced gas transfer factor and with airways obstruction in more severe cases. Many individuals reporting significant disability had only slightly abnormal ventilatory function tests at rest. Radiographic changes were found at survey in about one-third of the subjects reporting disability. Many farmers had not used an efficient mask. Treatment is unsatisfactory but steroid therapy is effective in acute episodes.