端粒 端粒酶与特发性肺间质纤维化

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF) 是一种病因不明、发病机制不清、缺乏有效治疗手段的弥漫性肺间质疾病,其病理特征是肺泡上皮损伤、成纤维细胞灶(fibroblast foci) 的形成以及细胞外基质的过度积聚,最终导致了肺泡结构的异常重塑[1,2].     

Environmental causes of violence

Violent and anti-social behavior is usually attributed to social factors, including poverty, poor education, and family instability. There is also evidence that many forms of violent behavior are more frequent in individuals of lower IQ. The role of exposure to environmental contaminants has received little attention as a factor predisposing to violent behavior. However a number of environmental exposures are documented to result in a common pattern of neurobehavioral effects, including lowered IQ, shortened attention span, and increased frequency of antisocial behavior. This pattern is best described for children exposed to lead early in life, but a similar pattern is seen upon exposure to polychlorinated biphenyls and methyl mercury. Although not as extensively studied, similar decrements in IQ are seen upon exposure to arsenic and secondhand smoke (SHS) exposure. Prenatal and postnatal SHS exposure is also associated with increased rates of conduct disorder and attention deficit hyperactivity. Recent evidence suggests that temporal trends in rates of violent crime in many nations are consistent with earlier preschool blood lead trends, with a lag of about 20 years. These ecologic correlations are consistent with many controlled studies suggesting that lead-exposed children suffer irreversible brain alterations that make them more likely to commit violent crimes as young adults. If this pattern is true for lead and other contaminants, the most effective way to fight crime may be to prevent exposure to these contaminants.     

Smad与肺纤维化

转化生长因子β(TGF-β) 是与肺纤维化关系较为密切的细胞因子。Smad蛋白为TGF-β受体后下游的主要信号转导因子,其中Smad3是纤维化疾病的重要介导者,Smad7是TGF-β信号转导途径的主要抑制性蛋白,它们的异常表达可影响TGF-β活性,进而改变纤维化进程。调控Smad3,Smad7的表达可能为治疗纤维化疾病提供一种新手段。     

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a rapidly progressive illness of unknown cause characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. Treatment at present remains largely supportive, with evidence that patients' satisfaction and survival may be improved by referral to centers specializing in the evaluation of interstitial lung diseases. Although no drug therapy has clearly been demonstrated to benefit patients with idiopathic pulmonary fibrosis, a number of novel investigational agents hold promise for future study. Given the poor prognosis associated with idiopathic pulmonary fibrosis, patients should be referred to regional centers of expertise for enrollment in therapeutic clinical trials or for lung transplantation.     

Immunolocalization of SPARC, tenascin, and thrombospondin in pulmonary fibrosis.

Several biochemically unrelated multifunctional extracellular proteins, SPARC, thrombospondin 1, and tenascin-C (TN), have been grouped as antiadhesive glycoproteins because they inhibit the spreading of cells on extracellular matrix in vitro. Migration of fibroblasts and epithelial cells into the air spaces to organize inflammatory exudate is a feature common to several fibrosing lung diseases. We hypothesized that migration would be facilitated by loosening the adhesive interactions between cells and the pericellular matrix components of the alveolar wall and that one or more of the anti-adhesive glycoproteins could be involved. Immunohistochemistry was used to localize SPARC, TN, and thrombospondin 1 in biopsies of organizing pneumonia, idiopathic pulmonary fibrosis (nine cases of usual interstitial pneumonia, one of desquamative interstitial pneumonia), and control lungs. Each antigen had a distinctive distribution. Only TN was expressed in control lungs, where it strongly stained the basement membrane of large bronchi and weakly stained alveolar entrance rings and small veins. In organizing pneumonia, TN was heavily stained through the entire extracellular matrix of the Masson bodies. In idiopathic pulmonary fibrosis, TN was abundant in the fibroblast foci of active fibrosis but was also present in the basement membrane regions beneath the metaplastic epithelium lining honeycomb cysts. TN was abundant in the interstitium in desquamative interstitial pneumonia. SPARC was observed only intracellularly where it occurred in the fibroblasts of Masson bodies of organizing pneumonia and the fibroblast foci of usual interstitial pneumonia. In desquamative interstitial pneumonia, expression of SPARC was minimal, in rare interstitial fibroblasts. Thrombospondin 1 was found consistently in organizing pneumonia but only infrequently in idiopathic pulmonary fibrosis. In both, it was localized in the extracellular matrix immediately beneath reparative epithelium. These results are consistent with a role for SPARC in fibroblast migration. TN may function in both fibroblast migration and the adhesion of metaplastic bronchial-type epithelium. However, these proteins also have other activities that may be important in pulmonary fibrosis. The localization of thrombospondin 1 suggests that it may be synthesized by regenerating epithelium where it may aid in the adhesion or migration of the epithelial cells.