Many of the cellular responses that occur in activated platelets resemble events that take place following activation of cell-death pathways in nucleated cells. We tested the hypothesis that formation of the mitochondrial permeability transition pore (MPTP), a key signaling event during cell death, also plays a critical role in platelet activation. Stimulation of murine platelets with thrombin plus the glycopro-tein VI agonist convulxin resulted in a rapid loss of mitochondrial transmem-brane potential (m) in a subpopulation of activated platelets. In the absence of cyclophilin D (CypD), an essential regulator of MPTP formation, murine platelet activation responses were altered. CypD-deficient platelets exhibited defects in phosphatidylserine externalization, high-level surface fibrinogen retention, membrane vesiculation, and procoagulant activity. Also, in CypD-deficient platelet-rich plasma, clot retraction was altered. Stimulation with thrombin plus H 2 O 2 , a known activator of MPTP formation, also increased high-level surface fibrinogen retention , phosphatidylserine externaliza-tion, and platelet procoagulant activity in a CypD-dependent manner. In a model of carotid artery photochemical injury, thrombosis was markedly accelerated in CypD-deficient mice. These results implicate CypD and the MPTP as critical regulators of platelet activation and suggest a novel CypD-dependent negative-feedback mechanism regulating arterial thrombosis. (Blood. 2008;111:1257-1265)

Chest radiographs of 101 patients with chronic airflow obstruction were assessed for evidence of over-inflation (increased retrosternal space, low diaphragm, and increased total lung capacity), pulmonary hypertension (increase in size of heart and major pulmonary vessels) and attenuation of medium-sized pulmonary vessels. The radiological abnormalities were related to the alterations in pulmonary function.When the position of the diaphragm was low or the retrosternal space was 4*5 cm or more the average FEV1 was below 1-0 litre, but severe impairment of the FEV1 could be present when the position and contour of the diaphragm were normal and the retrosternal space was 2 5 cm or less. The radiological method for estimating total lung capacity agreed well with the results obtained with body plethysmography, but there was not a close correlation between the standard radiological signs of over-inflation and a large total lung capacity.When the radiograph showed widespread vascular attenuation as well as over-inflation the impairment in FEV1 and other tests of pulmonary function was considerably more severe than when the radiograph showed over-inflation alone. Severe reduction in transfer factor was usually associated with changes in the pulmonary vessels.It is concluded that the radiological diagnosis of widespread emphysema can be made with confidence only when there is attenuation of pulmonary vessels as well as evidence of overinflation. In attempting to diagnose emphysema in life all available clinical and functional data should be considered in conjunction with the radiographic appearances.Potentially radiology offers the simplest and most widely applicable method for diagnosing emphysema in life, but there is controversy about its accuracy and sensitivity. Burrows et al. (1966) found they could predict reliably the presence of emphysema in patients with severe airflow obstruction by using a combination of abnormalities in the chest radiograph (areas of attenuation of medium-sized pulmonary arteries) and in pulmonary function (a low transfer factor per litre lung volume and a low Pco2 in relation to the severity of airways obstruction). In contrast, Sutinen, Christoforidis, Klugh, and Pratt (1965) have claimed that radiological evidence of 'overinflation' (a low diaphragm and an enlarged retrosternal space) alone is sufficient to diagnose emphysema. In this paper we attempt to assess the functional significance of the radiological signs of over-inflation and vascular attenuation by comparing these signs with the abnormalities in pul- (b) Size of the retrosternal space: On the lateral radiograph the distance from the posterior aspect of the sternum 3 cm below the sterno-manubrial junction horizontally to the anterior margin of the aorta was measured.

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