Rationale: The airflow limitation that defines severity of chronic obstructive pulmonary disease (COPD) is caused by a combination of small airway obstruction and emphysematous lung destruction. Objectives: To examine the hypothesis that small airway obstructive and emphysematous destructive lesions are produced by differential expression of genes associated with tissue repair. Methods: The expression of 54 genes associated with repair of repetitively damaged tissue was measured in 136 paired samples of small bronchioles and surrounding lung tissue separated by laser capture microdissection. These samples were collected from 63 patients at different levels of disease severity who required surgery for either lung cancer or lung transplantation for very severe COPD. Gene expression was measured by quantitative polymerase chain reaction in these paired samples and compared with the FEV 1 by linear regression analysis. Measurements and Main Results: After corrections for false discovery rates, only 2 of 10 genes (serpin peptidase inhibitor/plasminogen activator inhibitor member 2 and matrix metalloproteinase [MMP] 10) increased, whereas 8 (MMP2, integrin-a1, vascular endothelial growth factor, a disintegrin and metallopeptidase domain 33, scatter factor/hepatocyte growth factor, tissue inhibitor of matrix metalloproteinase-2, fibronectin, and collagen 3a1) decreased in small airways in association with FEV 1 . In contrast, 8/12 genes (early growth response factor 1, MMP1, MMP9, MMP10, plasminogen activator urokinase, plasminogen activator urokinase receptor, tumor necrosis factor, and IL13) increased and 4/12 (MMP2, tissue inhibitor of matrix metalloproteinase-1, collagen 1a1, and transforming growth factor-b3) decreased in the surrounding lung tissue in association with progression of COPD. Conclusions: The progression of COPD is associated with the differential expression of a cluster of genes that favor the degradation of the tissue surrounding the small conducting airways.

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gastroenteritis and other toxic conditions in infants there was extreme hyperuricaemia-20 mg/100 ml was often recorded. With such levels precipitation of urate in the kidney had to be considered.To investigate this possibility experimental production of the syndrome was, effected in rats by blocking the uricase activity with oxonic acid.3 By application of sublethal tourniquet shock in these animals we regularly found hyperuricaemia and massive uric acid precipitation in the renal tubules.4It is possible that "shock" kidney is provoked by this mechanism, and the particular purine metabolism of man may also be the explanation of his special proneness to kidney damage in shock. Forty-eight patients were studied. In 18 patients 24-hour urine collections were made for seven days following an injection of sodium aurothiomalate (Myocrisin) 50 mg. In the other 30 patients a 24-hour urine collection was made during either the second, third, fourth, fifth, or sixth day after injection, selected at random. Aliquots of urine samples and of standard gold solution were irradiated for five minutes in a thermal neutron flux of 1.3 x 1013 neutrons/cm2/second in the DIDO reactor (UKAEA, Harwell). After allowing the 24Na to decay to an acceptable level, the '98Au radioactivity was measured by gamma ray spectrometry.The seven-day excretion studies (18 patients) showed a remarkably flat curve (Fig. 1). In only one patient was a high excretion rate observed (Fig. 2). In this patient most of the injected gold was excreted within the first week, and probably a therapeutic level could not be achieved on conventional dosage. Apart from this patient, the maximum daily excretion of gold during a seven-day period of observation (Fig. 3), the mean daily excretion rate during the second to sixth day following injection, and the daily excretion rate of random 24-hour sample. during the same period (Fig. 4) all showed variation within a relatively narrow range only.We conclude that following an injection of sodium aurothiomalate for rheumatoid arthritis in most patients the gold is excreted slowly and fairly uniformly. In our experience, the type of hyperexcretion envisaged by Smith et al.I is a rare occurrence.We thank the East Anglian Regional Hospital Board who sponsored this research, and Messrs.May and Baker who contributed to the cost of the activation analysis.-We are, etc., R.

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