Search

Introduction: A major focus of interstitial lung disease (ILD) has centered on disorders termed idiopathic interstitial pneumonias (IIPs) which include, among others, idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, and respiratory bronchiolitis-interstitial lung disease., Areas Covered: We review the radiologic and histologic patterns for the nine disorders classified by multidisciplinary approach as IIP, and describe the remarkable amount of published epidemiologic, translational, and molecular studies demonstrating their associations with numerous yet definitive environmental exposures, occupational exposures, pulmonary diseases, systemic diseases, medication toxicities, and genetic variants., Expert Opinion: In the 21st century, these disorders termed IIPs are rarely idiopathic, but rather are well-described radiologic and histologic patterns of lung injury that are associated with a wide array of diverse etiologies. Accordingly, the idiopathic nomenclature is misleading and confusing, and may also promote a lack of inquisitiveness, suggesting the end rather than the beginning of a thorough diagnostic process to identify ILD etiology and initiate patient-centered management. A shift toward more etiology-focused nomenclature will be beneficial to all, including patients hoping for better life quality and disease outcome, general medicine and pulmonary physicians furthering their ILD knowledge, and expert ILD clinicians and researchers who are advancing the ILD field.

Alveolar epithelial cell loss and impaired epithelial cell regeneration are currently accepted as central initiating events in idiopathic pulmonary fibrosis (IPF), but subsequent downstream effects remain uncertain. The most accepted downstream effect is aberrant and dysregulated mesenchymal cell proliferation and excess extracellular matrix (ECM) accumulation. However, biochemical and imaging studies have perhaps somewhat surprisingly indicated little increase in total lung collagen and lung tissue, and have rather shown a substantial decrease in lung aeration and lung air volume. Loss of tissue aeration is a consequence of alveolar collapse, which occurs in IPF as a result of apposition and septal incorporation of denuded basal lamina. Permanent alveolar collapse is well-documented following epithelial injury, has the ability to mimic interstitial fibrosis radiologically and histologically, and is a better supported explanation than dysregulated fibroblast proliferation and excess ECM accumulation for the constellation of findings in patients with IPF.

Unlabelled: Cytokines modulate the course of autoimmunity, but their role in the evolution of spontaneous disease is unclear. This study compared the cytokine kinetics of T cell cultures from thyroiditis (LT)-prone NB line BB/Wor rats with those of Wistar (Wis) rat controls following activation with the thyroid-specific antigen thyroglobulin (Tg) or Concanavalin A (Con A)., Design: T cell enhanced splenocytes from 60 day old Wis and NB rats were activated with 0.5 microg/ml rat thyroglobulin (Tg) or Con A in the presence of homologous irradiated splenocytes as antigen presenting cells (APC's). In addition, the effect of APC's was determined in a crisscross experiment which examined NB T cell responses to Con A in the presence of Wis APC's. ELISA and RT-PCR were used to examine IL-2, IL-4, IL-10, TNFalpha, IFNgamma, IL-I0 concentrations and mRNA expression in the supernatant and cells from parallel cultures harvested at specific intervals. Frozen thyroids from 60 day old NB, Wis and Fisher rats were examined for the presence of IL-10 by immunohistochemistry. T cell proliferation was measured by 3H thymidine uptake., Results: Following activation with either Tg or Con A, IL-10 concentrations exceeded IFNgamma in NB rat cultures, but IFNgamma exceeded IL-10 in Wis cultures. Wis splenocytes significantly enhanced NB T cell proliferation and cytokine responses to Con A. Thyroids from 60 day NB rats contained IL-10, but no IFNgamma. There was no IL-10 in thyroids from Wistar or Fisher rats., Conclusion: Splenocyte responses in LT-prone BB/Wor rats favor IL-10 production. Future investigations will examine the source of intrathyroidal IL-10 and its role in LT.

Amplification of a product in PCR with specific primers may be viewed as an artificial Darwinian-type "selection of the fittest". In other selective systems, such as general evolution, immune system and probably brain cortex, the stringency of selection is not absolute but rather degenerate, with selection of many highly fit units, not limited, however, to only the fittest. In PCR also, annealing of the primers is not absolutely specific. The subsequent amplification frequently leads to amplification of not only the desired product but also to less-specific sequences. Using theoretical analysis of the degenerate mode of selection, we predict theoretically and prove experimentally that 5'-degenerate, 3'-dideoxy-terminated competitors of PCR primers can be used to dramatically improve the specificity of PCR amplification without affecting the quantitation of the final specific product.