45 research outputs found

    Year in review in Intensive Care Medicine, 2008: II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation

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    On the arc transition mechanism in nanosecond air discharges

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    International audienceNanosecond repetitively pulsed discharges can be classified into three types: the corona, the glow and the spark. The experimental parameters triggering the transition between these regimes are well understood. Corona and glow are non-equilibrium plasmas. The spark plasma can be in non-equilibrium or in equilibrium, the equilibrium regime being called hereafter the arc regime. The transition from the non-equilibrium spark to the arc regime for nanosecond discharges is not entirely understood. This is accompanied by a sharp rise of the gas temperature and electron number density that cannot be explained by conventional mechanisms. In this paper, spatially and temporally resolved emission was performed before, during and after the arc transition, which was found on a time scale below 1 ns. We compare the measurements of the electron number density and the electronic temperature before and after the transition. According to the present results, the electron number density rises from typical values of 10 15 to 10 19 cm-3 and the gas temperature increases from 1,000 K to 40,000 K. The presented measurements are intended to help explain the transition mechanism

    Presence of Rheumatoid Factor during Chronic HCV Infection Is Associated with Expansion of Mature Activated Memory B-Cells that Are Hypo-Responsive to B-Cell Receptor Stimulation and Persist during the Early Stage of IFN Free Therapy

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    <div><p>Approximately half of those with chronic hepatitis C virus (HCV) infection have circulating rheumatoid factor (RF), and a portion of these individuals develop cryoglobulinemic vasculitis. B cell phenotype/function in relation to RF in serum has been unclear. We examined B cell subset distribution, activation state (CD86), cell cycle state (Ki67), and ex-vivo response to BCR, TLR9 and TLR7/8 stimulation, in chronic HCV-infected donors with or without RF, and uninfected donors. Mature-activated B-cells of HCV-infected donors had lower CD86 expression compared to uninfected donors, and in the presence of RF they also showed reduced CD86 expression in response to BCR and TLR9 stimulation. Additionally, mature activated memory B cells of HCV RF+ donors less commonly expressed Ki67<sup>+</sup> than HCV RF- donors, and did not proliferate as well in response to BCR stimulation. Proportions of mature-activated B cells were enhanced, while naïve B-cells were lower in the peripheral blood of HCV-RF+ compared to RF- and uninfected donors. None of these parameters normalize by week 8 of IFN free direct acting antiviral (DAA) therapy in HCV RF+ donors, while in RF- donors, mature activated B cell proportions did normalize. These data indicate that while chronic HCV infection alone results in a lower state of activation in mature activated memory B cells, the presence of RF in serum is associated with a more pronounced state of unresponsiveness and an overrepresentation of these B cells in the blood. This phenotype persists at least during the early time window after removal of HCV from the host.</p></div

    Untreated study donor characteristics.

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    <p>Values are expressed as median (range) for age, HCV RNA level, albumin, platelet, AST level, ALT level, APRI score, calculated as described previously [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144629#pone.0144629.ref047" target="_blank">47</a>], and absolute CD19+ count. Numbers and proportions of subjects within each category are given for HCV genotype, duration of HCV infection, sex, ethnicity and RF. Abbreviations: ALT, alanine aminotransferase; APRI, AST-to-Platelet ratio index; AST, aspartate aminotransferase; HCV, hepatitis C virus, and RF, rheumatoid factor. <sup>a</sup> p< .05 compared with uninfected donors; <sup>b</sup> p< .05 compared between HCV RF- and HCV RF+</p><p>Untreated study donor characteristics.</p

    HCV RF+ (donors have greater proportions of mature activated memory B cells and reduced proportions of naïve B cells in comparison to uninfected donors and HCV RF- donors.

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    <p><b>(</b>A) Absolute count of CD19+ B cell per uL of whole blood. (B) Representative flow plot of altered B cell subset distribution in whole blood from Uninfected donor, HCV RF-, and HCV RF+ donors. (C) Summary data of Proportion of mature activated memory B cells (%) in whole blood (CD19+CD20+CD10-CD21-/loCD27+) for Uninfected donors (<b>▄ n = 23)</b>, HCV RF- <b>(● n = 23)</b>, and HCV RF+ donors (<b>▼, n = 20).</b> (D). Summary data of Proportion of naïve B cells (CD19+CD20+CD10-CD21+CD27-) in whole blood for Uninfected donors (<b>▄ n = 23)</b>, HCV RF- <b>(● n = 23)</b>, and HCV RF+ donors (<b>▼, n = 20)</b>. Kruskal- Wallis was used to analyzed differences among the three groups of donors and Mann-Whitney U test was used between two groups of donors (p≤0.05)</p

    Increased viral load in HCV RF+ donors and gating strategy to enumerate B cell subset frequencies from whole blood.

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    <p><b>(</b>A), HCV RNA copies IU/mL HCV RF- (●, n = 23) and HCV RF+ (▼, n = 23). <b>(</b>B) Shown an uninfected donor sample for total immature transitional B cells (CD19+CD20+CD10+) and its differentiation stages: T1 stage (CD19<sup>+</sup>CD20<sup>+</sup>CD10<sup>+</sup>CD21-) and T2 stage (CD19<sup>+</sup>CD20<sup>+</sup>CD10<sup>+</sup>CD21<sup>+</sup>). Mature activated B cells(CD19<sup>+</sup>CD20<sup>+</sup>CD10<sup>-</sup>CD21<sup>-</sup>CD27<sup>+</sup>), resting memory B cells (CD19<sup>+</sup>CD20<sup>+</sup>CD21<sup>+</sup>CD27<sup>+</sup>), naïve (CD19<sup>+</sup>CD20<sup>+</sup>CD21<sup>+</sup>CD27<sup>-</sup>),Tissue like memory B cells (CD19<sup>+</sup>CD20<sup>+</sup>CD10<sup>-</sup>CD21<sup>-</sup>CD27<sup>-</sup>) and Plasmablast cells (CD19<sup>+</sup>CD20<sup>-</sup>CD38<sup>+</sup>)</p

    Mature activated memory B cells of HCV donors show low CD86 expression and have limited response to BCR stimulation in HCV RF+ donors.

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    <p><b>(</b>A-B) Representative and summary for CD86 expression in whole blood of uninfected donors (UD <b>▄</b> n = 23), HCV Rheumatoid Factor negative (HCV RF-, <b>●</b> n = 23) and HCV Rheumatoid Factor positive (HCV RF+, <b>▼</b> n = 20). (C-D) Representative and summary data of CD86 ex vivo experiments, where peripheral blood mononuclear cells were cultured for 3 days in medium alone, anti IgG F(ab’)<sup>2</sup> fragment (4ug/mL), CpG (1ug/mL), R848 (Iug/mL) and cells were stained for B cell subset markers and CD86. UD(▄, n = 15), HCV RF- (●, n = 14), HCV RF+ (▼, n = 15). Kruskal- Wallis was used to analyzed differences among the three groups (*) of donors and Mann-Whitney U test (p≤0.05) was used between two groups of donors.</p

    Mature activated memory B cells of HCV RF+ donors have decreased ki-67 and are less likely to proliferate in response to BCR stimulation.

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    <p><b>(</b>A-B) Representative and summary for Ki-67expression in whole blood of uninfected donors (UD <b>▄</b> n = 23), HCV RF- (<b>●</b> n = 20) and HCV RF+ (<b>▼</b> n = 20). (C-D) Representative and summary data of CFSE dye dilution of ex vivo experiments, where peripheral blood mononuclear cells were cultured for 6 days in medium alone, anti BCR (anti IgG F(ab’)<sup>2</sup> fragment, 4ug/mL), CpG 2006 (1ug/mL), R848 (Iug/mL) and cells were stained for B cell subset markers. UD(▄, n = 11), HCV RF- (●, n = 11), HCV RF+ (▼, n = 10). Kruskal- Wallis was used to analyzed differences among the three groups (*) of donors and Mann-Whitney U test (p≤0.05) was used between two groups of donors.</p
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