Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis.

The etiology of Riedel's invasive fibrous thyroiditis (IFT) has remained obscure. This rare disorder has been confused in the past with the more common fibrous variant of Hashimoto's disease. The typical histological features of IFT, in particular the presence of an invasive fibrosclerotic process in conjunction with a prominent chronic inflammatory infiltrate, suggest that the release of fibrogenic cytokines and other factors from these cellular infiltrates may play an important role in the pathogenesis of this condition. Our observations in routinely processed tissue sections obtained from patients with documented IFT of striking tissue eosinophilia led us to hypothesize that eosinophils and their products may play a role in the evolution of this disease. Immunofluorescence staining with affinity-purified polyclonal rabbit antibody directed against human eosinophil granule major basic protein revealed marked tissue eosinophilia and abundant extracellular deposition of major basic protein in all specimens from 16 patients with IFT. By contrast, only occasional eosinophils and no extracellular major basic protein were detected in control thyroid tissues obtained from patients with multinodular goiter, Graves' disease, Hashimoto's disease, and normal thyroid tissue. The presence of marked eosinophil infiltration and extracellular major basic protein deposition in IFT and other associated fibrosclerotic conditions suggests a role for eosinophils and their products in propagating the fibrogenesis seen in IFT

Tissue eosinophilia induced by recombinant human interleukin-5 in the hamster cheek pouch membrane

Interleukin-5 (IL-5) is a cytokine that preferentially effects the development and function of eosinophils, and is considered important in the pathophysiology of allergic inflammation. In this study, we evaluated the ability of recombinant human IL-5 (rHu IL-5) to promote tissue eosinophilia and the importance of this eosinophilia to pathological alterations in vascular function. Repetitive subcutaneous administration for 18 days of rHu IL-5 resulted in a 7-fold increase in the number of eosinophils found in the ipsilateral hamster cheek pouch membrane. The contralateral cheek pouch membrane and peritoneum of these animals showed lesser but significant elevations in the number of eosinophils. In contrast, denatured rHu IL-5 did not elevate eosinophils in these tissues. Through the use of intravital microscopy and fluorometric analysis, rHu IL-5 treated hamster cheek pouch membranes were evaluated for alterations in microvascular permeability, using plasma clearance of FITC-dextran 150 as an index. Despite promoting a prominent tissue eosinophilia, the repetitive subcutaneous injections of rHu IL-5 did not alter the clearance of FITC-dextran 150. Topical application of rHu IL-5 to the cheek pouch, also, had no effect on the clearance of FITC-dextran 150. Immunofluorescence observations using an antibody to the granule protein, eosinophil peroxidase, indicated that the recruited cells had not degranulated. Our results support the importance of IL-5 in the recruitment of tissue eosinophils, but further stimulation is probably required to cause degranulation of these cells and the ensuing tissue damage

The physics of spreading processes in multilayer networks

The study of networks plays a crucial role in investigating the structure, dynamics, and function of a wide variety of complex systems in myriad disciplines. Despite the success of traditional network analysis, standard networks provide a limited representation of complex systems, which often include different types of relationships (i.e., "multiplexity") among their constituent components and/or multiple interacting subsystems. Such structural complexity has a significant effect on both dynamics and function. Throwing away or aggregating available structural information can generate misleading results and be a major obstacle towards attempts to understand complex systems. The recent "multilayer" approach for modeling networked systems explicitly allows the incorporation of multiplexity and other features of realistic systems. On one hand, it allows one to couple different structural relationships by encoding them in a convenient mathematical object. On the other hand, it also allows one to couple different dynamical processes on top of such interconnected structures. The resulting framework plays a crucial role in helping achieve a thorough, accurate understanding of complex systems. The study of multilayer networks has also revealed new physical phenomena that remain hidden when using ordinary graphs, the traditional network representation. Here we survey progress towards attaining a deeper understanding of spreading processes on multilayer networks, and we highlight some of the physical phenomena related to spreading processes that emerge from multilayer structure.Comment: 25 pages, 4 figure

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease