Higher oesophageal temperature at rest and during exercise in humans with patent foramen ovale.

Respiratory system cooling occurs via convective and evaporative heat loss, so right-to-left shunted blood flow through a patent foramen ovale (PFO) would not be cooled. Accordingly, we hypothesized that PFO+ subjects would have a higher core temperature than PFO- subjects due, in part, to absence of respiratory system cooling of the shunted blood and that this effect would be dependent upon the estimated PFO size and inspired air temperature. Subjects were screened for the presence and size of a PFO using saline contrast echocardiography. Thirty well-matched males (15 PFO-, 8 large PFO+, 7 small PFO+) completed cycle ergometer exercise trials on three separate days. During Trial 1, subjects completed a V̇(O2max) test. For Trials 2 and 3, randomized, subjects completed four 2.5 min stages at 25, 50, 75 and 90% of the maximum workload achieved during Trial 1, breathing either ambient air (20.6 ± 1.0°C) or cold air (1.9 ± 3.5°C). PFO+ subjects had a higher oesophageal temperature (T(oesoph)) (P < 0.05) than PFO- subjects on Trial 1. During exercise breathing cold and dry air, PFO+ subjects achieved a higher T(oesoph) than PFO- subjects (P < 0.05). Subjects with a large PFO, but not those with a small PFO, had a higher T(oesoph) than PFO- subjects (P < 0.05) during Trial 1 and increased T(oesoph) breathing cold and dry air. These data suggest that the presence and size of a PFO are associated with T(oesoph) in healthy humans but this is explained only partially by absence of respiratory system cooling of shunted blood.

IFN-alpha2 induces leukocyte integrin redistribution, increased adhesion, and migration.

The human type I Interferon (IFN) family includes 14 closely related cytokines that are produced in response to viral and bacterial infections and mediate the progress of innate immune responses to adaptive immune protection, bind to a common receptor, and have qualitatively similar biologic activities. We have shown previously that IFN-alpha2 can induce human T cell chemotaxis, suggesting that type I IFNs may contribute to the development of an inflammatory environment. We here report that, in addition to promoting T cell chemotaxis, IFN-alpha2 enhances T cell adhesion to integrin ligands, which is associated with integrin clustering on the T cell surface and enhanced conjugate formation with dendritic cells. These effects were prevented by inhibition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K). As type I IFN receptor is ubiquitously expressed, this analysis was extended to other human leukocyte populations, including granulocytes and B cells. All leukocyte populations analyzed displayed increased chemotaxis, integrin clustering, and increased integrin-mediated adhesion following exposure to IFN-alpha2, revealing a broad-spectrum proinflammatory activity. These findings have obvious implications for the role of type I IFNs in the development of inflammatory responses leading to the initiation of adaptive immunity.

Modulation of dendritic cell phenotype and function in an in vitro model of the intestinal epithelium.

A network of dendritic cells (DC) can be detected in close proximity to the epithelial cells overlying Peyer's patches in the gut. Intestinal DC show distinct phenotypes as compared to DC from the systemic lymph nodes (relatively low MHC and costimulatory molecules and high IL-10 and TGFbeta) and may play a role in maintaining tolerance to enteric antigens. We show that a similar phenotype is induced in the presence of a polarised epithelial cell monolayer in vitro. Monocyte-derived DC were co-cultured with Caco-2 intestinal epithelial monolayers for 24 h. Co-culture resulted in DC with reduced expression of MHC class II, CD86, and CD80, and poor T cell stimulatory capacity. Cytokine profiles showed reduced levels of inflammatory cytokine production, and co-cultured DC were less sensitive to stimulation via Toll-like receptors (TLR2, 4, and 6) as a result of increased levels of autocrine TGFbeta production. However, phenotypic changes in co-cultured DC could not be blocked by removal of apoptotic cells or addition of anti-TGFbeta antibodies, suggesting that other soluble factors are involved in DC modulation. Thus, polarised epithelial cell monolayers create a 'tolerogenic' environment which modulates the activity of DC. These results highlight the regulatory importance of the epithelial microenvironment at mucosal surfaces.

Equal appearing interval and visual analogue scaling of perceptual roughness and breathiness.

One of the factors that affects the reliability of perceptual voice evaluation is the rating scale. Equal-appearing interval (EAI) and visual analogue (VA) scales are the two most common scales used and have attracted much attention in recent studies of perceptual voice evaluation. Available findings are contradictory, with one study finding the EAI scale to be more desirable while an earlier study showed equivocal results. The objective of the present study was to compare the reliability of using an 11-point EAI scale and a VA scale, each of 10cm long, for perceptual voice quality evaluation. Thirty listeners with no prior experience in perceptual voice evaluation were asked to rate the breathy and rough qualities of 28 voice samples. The results showed that the listeners demonstrated a significantly higher intra-rater agreement and lower inter-rater variability in rating the two perceptual voice qualities using the EAI scale, when compared to the VA scale. However, listeners tend to show more bias in using certain points on the EAI scale than on the VA scale. In addition, a linear relationship was found between the EAI and VA ratings, suggesting the psychoperceptual characteristics of breathy and rough qualities could be captured equally well by the EAI and VA scales. Since the ease of use of the rating scale is an important consideration in clinical situations, the 11-point, 10cm long EAI scale is therefore more preferable, although not necessarily more superior, than the VA scale for evaluating breathy and rough qualities.