William Dwight Whitney and the Science of Language

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Altered distribution of mucosal NK cells during HIV infection.

The human gut mucosa is a major site of human immunodeficiency virus (HIV) infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells have an important role in control of HIV infection, but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here, we show that two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (intraepithelial lymphocytes, IELs) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective killer immunoglobulin-like receptor/human leukocyte antigen genotypes. Both IEL and LP NK cells were significantly expanded in immunological non-responsive patients, who incompletely recovered CD4+ T cells on highly active antiretroviral therapy (HAART). These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T-cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut

Changes in Natural Killer Cell Activation and Function during Primary HIV-1 Infection

Background: Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection. Methodology/Principal Findings: Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, α$_4$β$_7$). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p = 0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r = 0.68;p<0.0001; post-infection, during primary infection r = 0.074;p = 0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r = 0.32'p = 0.04 and r = 0.35;p = 0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIR$_{pos}$) NK cells increased following HIV acquisition (p = 0.006), and KIR$_{pos}$ NK cells were less activated than KIR$_{neg}$ NK cells amongst individuals sampled while seronegative or serodiscordant (p = 0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p = 0.006 and p = 0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001). Conclusions/Significance: Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue

Comment on ``Protective measurements of the wave function of a single squeezed harmonic-oscillator state''

Alter and Yamamoto [Phys. Rev. A 53, R2911 (1996)] claimed to consider ``protective measurements'' [Phys. Lett. A 178, 38 (1993)] which we have recently introduced. We show that the measurements discussed by Alter and Yamamoto ``are not'' the protective measurements we proposed. Therefore, their results are irrelevant to the nature of protective measurements.Comment: 2 pages LaTe

Emerging infectious disease issues in blood safety.

Improvements in donor screening and testing and viral inactivation of plasma derivatives together have resulted in substantial declines in transfusion-transmitted infections over the last two decades. Most recently, nucleic acid testing techniques have been developed to screen blood and plasma donations for evidence of very recent viral infections that could be missed by conventional serologic tests. Nonetheless, the blood supply remains vulnerable to new and reemerging infections. In recent years, numerous infectious agents found worldwide have been identified as potential threats to the blood supply. Several newly discovered hepatitis viruses and agents of transmissible spongiform encephalopathies present unique challenges in assessing possible risks they may pose to the safety of blood and plasma products

Triage for coronary artery bypass graft surgery in Canada: Do patients agree on who should come first?

<p>Abstract</p> <p>Background</p> <p>The extent to which clinical and non-clinical factors impact on the waiting-list prioritization preferences of patients in the queue is unknown. Using a series of hypothetical scenarios, the objective of this study was to examine the extent to which clinical and non-clinical factors impacted on how patients would prioritize others relative to themselves in the coronary artery bypass surgical queue.</p> <p>Methods</p> <p>Ninety-one consecutive eligible patients awaiting coronary artery bypass grafting surgery at Sunnybrook Health Sciences Centre (median waiting-time duration prior to survey of 8 weeks) were given a self-administered survey consisting of nine scenarios in which clinical and non-clinical characteristic profiles of hypothetical patients (also awaiting coronary artery bypass surgery) were varied. For each scenario, patients were asked where in the queue such hypothetical patients should be placed relative to themselves.</p> <p>Results</p> <p>The eligible response rate was 65% (59/91). Most respondents put themselves marginally ahead of a hypothetical patient with identical clinical and non-clinical characteristics as themselves. There was a strong tendency for respondents to place patients of higher clinical acuity ahead of themselves in the queue (P < 0.0001). Social independence among young individuals was a positively valued attribute (P < 0.0001), but neither age per se nor financial status, directly impacted on patients waiting-list priority preferences.</p> <p>Conclusion</p> <p>While patient perceptions generally reaffirmed a bypass surgical triage process based on principals of equity and clinical acuity, the valuation of social independence may justify further debate with regard to the inclusion of non-clinical factors in waiting-list prioritization management systems in Canada, as elsewhere.</p

Antibody glycosylation in inflammation, disease and vaccination

Immunogenetics and cellular immunology of bacterial infectious disease