Dsg1 plays an important role in maintaining adhesion in differentiating keratinocytes. As the programme of cell death provides for the disruption of intercellular contacts, we wondered whether apoptotic cells weaken Dsg1 function also by reducing its synthesis. To test this working hypothesis, we carried out reverse transcription-polymerase chain reaction analysis on RNA from keratinocytes exposed to 800 nmol L )1 STS at selected time points. Results showed that the programme of cell death triggered by STS targets Dsg1 not by acting at a transcriptional level (Fig. 3).Our data disagree with those reported by Dusek et al. 5 and discussed above. Indeed, apoptotic cleavage of Dsg1 resulted in the formation of two proteolytic products of about 60 and 100 kDa. An explanation could be that Dsg1 is processed by effector caspases other than caspase-3, such as caspase-6 or caspase-7. Dusek et al. have shown the latter to be inefficient in cleaving Dsg1, but it is known that discrepancies exist between cleavage preferences in vitro and substrate cleavage sites actually found. 8 Furthermore, under our experimental conditions we were not able to demonstrate the extracellular cleavage of Dsg1 by metalloproteinases and the subsequent shedding from the cell surface as a 75-kDa fragment.The present study is conceptually in line with a view of apoptosis as a complex and finely orchestrated process subjected to an exquisite regulation. Very similar stimuli can differentially activate both the intrinsic and extrinsic pathways. 9 Conversely, distinct stimuli can trigger the same apoptotic signalling. Our results, however, suggest that the mitochondria-dependent (i.e. intrinsic) cascade can lead to a differential processing of target proteins depending on the nature of the apoptotic stimulus. In this case, we have reported that cleavage of Dsg1 during STS-induced apoptosis differs from that described with other 'intrinsic' apoptotic inducers.A. LANZA

BACKGROUND The lung is not considered a target organ in diabetes mellitus. In English language literature there are many papers showing the opposite. DISCUSSION Many studies demonstrated a thickened alveolar epithelial and pulmonary capillary basal lamina and a reduced lung elasticity, others showed that these histopathological alterations develop into functional abnormalities such as reduced lung volumes, pulmonary diffusion capacity and elastic recoil. The diabetes related pulmonary disease has not an impact on normal life in otherwise “healthy” patients, but it is possible that in specific pathologic (such as heart, kidney and lung comorbidities) or paraphysiologic (such as physical exercise, smoking or exposure to high altitude) conditions, diabetes could contribute to the clinical manifestation of a restricitive lung disease. On the other hand, diabetic patients have an increased propensity to acquire infections. The prevalence of pulmonary tuberculosis is reported to be four times than in healthy subjects; there is a predilection for the lower lobes and the disease is more aggressive in poorly controlled diabetes mellitus.

No abstract

Inflammatory bowel disease is a systemic illness that may involve the lung. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage data show an increase percentage of neutrophils and steroids are very effective in the majority of cases. Some patients present severe tracheal inflammation and obstruction with an inflammatory mass bulging into the tracheal lumen. Others show a small airway involvement with or without bronchiolitis obliterans organizing pneumonia pattern and have an equivocal response to steroids. In recent years many investigators demonstrated latent pulmonary involvement with a reduction in lung transfer factor and a small airways disorders.

No abstract