Rhinitis in the geriatric population

The current geriatric population in the United States accounts for approximately 12% of the total population and is projected to reach nearly 20% (71.5 million people) by 2030[1]. With this expansion of the number of older adults, physicians will face the common complaint of rhinitis with increasing frequency. Nasal symptoms pose a significant burden on the health of older people and require attention to improve quality of life. Several mechanisms likely underlie the pathogenesis of rhinitis in these patients, including inflammatory conditions and the influence of aging on nasal physiology, with the potential for interaction between the two. Various treatments have been proposed to manage this condition; however, more work is needed to enhance our understanding of the pathophysiology of the various forms of geriatric rhinitis and to develop more effective therapies for this important patient population

Single-Molecule Analysis Reveals the Kinetics and Physiological Relevance of MutL-ssDNA Binding

DNA binding by MutL homologs (MLH/PMS) during mismatch repair (MMR) has been considered based on biochemical and genetic studies. Bulk studies with MutL and its yeast homologs Mlh1-Pms1 have suggested an integral role for a single-stranded DNA (ssDNA) binding activity during MMR. We have developed single-molecule Förster resonance energy transfer (smFRET) and a single-molecule DNA flow-extension assays to examine MutL interaction with ssDNA in real time. The smFRET assay allowed us to observe MutL-ssDNA association and dissociation. We determined that MutL-ssDNA binding required ATP and was the greatest at ionic strength below 25 mM (KD = 29 nM) while it dramatically decreases above 100 mM (KD>2 µM). Single-molecule DNA flow-extension analysis suggests that multiple MutL proteins may bind ssDNA at low ionic strength but this activity does not enhance stability at elevated ionic strengths. These studies are consistent with the conclusion that a stable MutL-ssDNA interaction is unlikely to occur at physiological salt eliminating a number of MMR models. However, the activity may infer some related dynamic DNA transaction process during MMR

Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression

Not all flavor expertise is equal : The language of wine and coffee experts

People in Western cultures are poor at naming smells and flavors. However, for wine and coffee experts, describing smells and flavors is part of their daily routine. So are experts better than lay people at conveying smells and flavors in language? If smells and flavors are more easily linguistically expressed by experts, or more "codable", then experts should be better than novices at describing smells and flavors. If experts are indeed better, we can also ask how general this advantage is: do experts show higher codability only for smells and flavors they are expert in (i.e., wine experts for wine and coffee experts for coffee) or is their linguistic dexterity more general? To address these questions, wine experts, coffee experts, and novices were asked to describe the smell and flavor of wines, coffees, everyday odors, and basic tastes. The resulting descriptions were compared on a number of measures. We found expertise endows a modest advantage in smell and flavor naming. Wine experts showed more consistency in how they described wine smells and flavors than coffee experts, and novices; but coffee experts were not more consistent for coffee descriptions. Neither expert group was any more accurate at identifying everyday smells or tastes. Interestingly, both wine and coffee experts tended to use more source-based terms (e.g., vanilla) in descriptions of their own area of expertise whereas novices tended to use more evaluative terms (e.g., nice). However, the overall linguistic strategies for both groups were en par. To conclude, experts only have a limited, domain-specific advantage when communicating about smells and flavors. The ability to communicate about smells and flavors is a matter not only of perceptual training, but specific linguistic training too

Molecular pathways in follicular lymphoma

Follicular lymphoma (FL) is one of the most common B-cell non-Hodgkin's lymphomas. The initiating genetic event found in approximately 90% of FL is the t(14;18), causing constitutive expression of the antiapoptotic BCL-2 protein. The exact secondary alterations leading to full FL development are still poorly defined. In this review, we address (i) the genetic pathways associated with tumorigenesis and progression of FL, (ii) the role of micro-environmental factors with emphasis on B-cell receptor ligands and (iii) lymphoma models in mice and what they teach us about lymphomagenesis in ma

Expression of the IL-6 gene induces differentiation of a human monoclonal EBV-transformed B cell line

To study the role of interleukin (IL)-6 as a growth and differentiation factor for Epstein-Barr virus (EBV)-transformed B lymphocytes, we transfected the cDNA coding for human IL-6 in a monoclonal IgG1-secreting EBV B cell line. Two independent clones were selected that constitutively secreted high amounts of IL-6. These clones showed enhanced levels of IL-6 and tumor necrosis factor alpha secretion when compared to non-IL-6 transfected controls. Moreover, they could efficiently be recovered from low cell density cultures in limiting dilutions when plated on a feeder layer of heterologous EBV B cells. IL-6-induced phenotypical changes comprised a significant rise in immunoglobulin secretion levels and enhanced membrane expression of CD25 (the beta chain of the IL-2 receptor) and of the B cell differentiation antigen CD40. IL-6-dependent down modulation of CD38 and of the adhesion structure VLA4 were also observed. Our data support the notion that IL-6 can serve as an growth and differentiation factor for EBV B cell

Expression of connective tissue growth factor in human renal fibrosis

Chronic renal failure may occur in etiologically diverse renal diseases and can be caused by hemodynamic, immunologic and metabolic factors. Initial damage may evoke irreversible scarring, which involves production of a number of proinflammatory and fibrogenic cytokines, including platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Connective tissue growth factor (CTGF), a cytokine of the family of growth regulators comprising sef10, cyr61, CTGF and nov, has recently been described in association with scleroderma and other scarring conditions. We investigated CTGF mRNA expression in 65 human renal biopsy specimens of various renal diseases by in situ hybridization. In control human kidney CTFG mRNA was mainly expressed in visceral epithelial cells, parietal epithelial cells, and some interstitial cells. Connective tissue growth factor was strongly up-regulated in the extracapillary and severe mesangial proliferative lesions of crescentic glomerulonephritis, IgA nephropathy, focal and segmental glomerulosclerosis and diabetic nephropathy. An increase in the number of cells expressing CTGF mRNA was observed at sites of chronic tubulointerstitial damage, which correlated with the degree of damage. in the tubulointerstitial area the majority of the CTGF mRNA positive cells coexpressed alpha-smooth muscle actin, and were negative for macrophage markers. Our results indicate that CTGF may be a common growth factor involved in renal fibrosi