5%); p = 0.0004), the plaque substrate for thrombosis was erosion. Healed infarcts were found in 37.5% of men v 22% of women (p = 0.01). Heart rupture was more common in women than in men (22% v 10.5%, p = 0.01). The distribution of infarcts, thrombus location, heart rupture, and healed infarcts was similar in cases of plaque rupture and plaque erosion. Conclusions-Plaque erosion is an important substrate for coronary thrombosis in patients dying of acute myocardial infarction. Its prevalence is significantly higher in women than in men. (Heart 1999;82:269-272)

Mitochondrial (mt)DNA defects , both deletions and tRNA point mutations , have been associated with cardiomyopathies. The aim of the study was to determine the prevalence of pathological mtDNA mutations and to assess associated defects of mitochondrial enzyme activity in dilated cardiomyopathy (DCM) patients with ultrastructural abnormalities of cardiac mitochondria. In a large cohort of 601 DCM patients we performed conventional light and electron microscopy on endomyocardial biopsy samples. Cases with giant organelles , angulated , tubular , and concentric cristae , and crystalloid or osmiophilic inclusion bodies were selected for mtDNA analysis. Mutation screening techniques , automated DNA sequencing, restriction enzyme digestion , and densitometric assays were performed to identify mtDNA mutations, assess heteroplasmy , and quantify the amount of mutant in myocardial and blood DNA. Of 601 patients (16 to 63 years; mean , 43.5 ؎ 12.7 years) , 85 had ultrastructural evidence of giant organelles , with abnormal cristae and inclusion bodies; 19 of 85 (22.35%) had heteroplasmic mtDNA mutations (9 tRNA, 5 rRNA , and 4 missense , one in two patients) that were not found in 111 normal controls and in 32 DCM patients without the above ultrastructural mitochondrial abnormalities. In all cases , the amount of mutant was higher in heart than in blood. In hearts of patients that later underwent transplantation , cytochrome c oxidase (Cox) activity was significantly lower in cases with mutations than in those without or controls (P ‫؍‬ 0.0008). NADH dehydrogenase activity was only slightly reduced in cases with mutations (P ‫؍‬ 0.0388) , whereas succinic dehydrogenase activity did not significantly differ between DCM patients with mtDNA mutations and those without or controls. The present study represents the first attempt to detect a morphological, easily identifiable marker to guide mtDNA mutation screening. Pathological mtDNA mutations are associated with ultrastructurally abnormal mitochondria, and reduced Cox activity in a small subgroup of non-otherwise-defined, idiopathic DCMs, in which mtDNA defects may constitute the basis for, or contribute to, the development of congestive heart failure. (Am J Pathol 1998, 153:1501-1510)

The binding of the receptor for advanced glycation end products (RAGE) with its ligands begins a sustained period of cellular activation and inflammatory signal amplification in different tissues and diseases. This binding could represent an as yet uninvestigated pathway of inflammatory reaction in the lung, where the presence of the receptor has been largely documented and advanced glycation end products (AGEs) are produced by nonenzymatic glycation and oxidation of proteins and lipids, driven by smoke and pollutants exposure or inflammatory stress. We immunohistochemically assessed the expression of RAGE and of its major proinflammatory ligands, N-e-carboxy-methyl-lysine, S100B and S-100A12 in normal lung and in nonneoplastic lung disorders including smoke-related airway disease, granulomatous inflammation, postobstructive damage and usual interstitial pneumonia. In normal lung low expression of the receptor was observed in bronchiolar epithelia, type II pneumocytes, macrophages and some endothelia. S100A12 and S100B were expressed, respectively, in granulocytes and in dendritic cells. Carboxy-methyl-lysine was present in bronchiolar epithelia and macrophages. In all pathological conditions associated with inflammation and lung damage overexpression of both the receptor and of AGEs was observed in bronchiolar epithelia, type II alveolar pneumocytes, alveolar macrophages and endothelia. RAGE overexpression was more evident in epithelia associated with inflammatory cell aggregates. Fibroblasts in usual interstitial pneumonia expressed both the receptor and AGEs. The number of S100A12 and S100B immunoreactive inflammatory cells was variable. S100A12 was also expressed in mononuclear inflammatory cells and in activated epithelia. The activation of the inflammatory pathway controlled by the RAGE is not specific of a single lung disease, however, it may be relevant as a nonspecific pathway of sustained inflammation in lung tissue, and on this basis therapeutic approaches based on receptor blockage can be envisaged.