Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection.

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9-90 kDa autologous proteins.

[Illustrations de La tragique expédition de Lapérouse et Langle] / [Non identifié] ; Vicomte Paul Fleuriot de Langle, aut. du texte

Comprend : [Couverture : le char de Neptune. Bateaux de Lapérouse et de Langle. Carte des terres de Polynésie et d'Australie.] [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [Carte double avant la p.10 de l'Avant-propos :] Voyages de Lapérouse 1785-1788 (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.80 :] J.F. Galaup de Lapérouse (...). P.A. Fleuriot de Langle (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.81 :] Manoir de Rosvilio, près Callac (Côtes-du-Nord) demeure du Chevalier de Langle (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.96 :] Louis XVI donne ses instructions aux chefs de l'expédition (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.97 :] Insulaires et cyclopes de l'île de Paques (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.160 :] Mouillage des frégates françaises devant l'île de Mowee (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.161 :] Costume des habitants de la baie de Langle, manche de Tartarie (.. .). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.192 :] Massacre de MM. De Langle, de Lamanon et de dix autres membres des deux équipages, à Tutuila, Océanie (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.193 :] Mémorial élevé à Tutuila, en 1887, par les soisn de la Marine française, en souvenir du 11 décembre 1787 (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008]

The emerging importance of the SPX domain-containing proteins in phosphate homeostasis

Plant growth and development are strongly influenced by the availability of nutrients in the soil solution. Among them, phosphorus (P) is one of the most essential and most limiting macro-elements for plants. In the environment, plants are often confronted with P starvation as a result of extremely low concentrations of soluble inorganic phosphate (Pi) in the soil. To cope with these conditions, plants have developed a wide spectrum of mechanisms aimed at increasing P use efficiency. At the molecular level, recent studies have shown that several proteins carrying the SPX domain are essential for maintaining Pi homeostasis in plants. The SPX domain is found in numerous eukaryotic proteins, including several proteins from the yeast PHO regulon, involved in maintaining Pi homeostasis. In plants, proteins harboring the SPX domain are classified into four families based on the presence of additional domains in their structure, namely the SPX, SPX-EXS, SPX-MFS and SPX-RING families. In this review, we highlight the recent findings regarding the key roles of the proteins containing the SPX domain in phosphate signaling, as well as providing further research directions in order to improve our knowledge on P nutrition in plants, thus enabling the generation of plants with better P use efficiency.

Promoter recognition and activation by the global response regulator CbrB in Pseudomonas aeruginosa.

In Pseudomonas aeruginosa, the CbrA/CbrB two-component system is instrumental in the maintenance of the carbon-nitrogen balance and for growth on carbon sources that are energetically less favorable than the preferred dicarboxylate substrates. The CbrA/CbrB system drives the expression of the small RNA CrcZ, which antagonizes the repressing effects of the catabolite repression control protein Crc, an RNA-binding protein. Dicarboxylates appear to cause carbon catabolite repression by inhibiting the activity of the CbrA/CbrB system, resulting in reduced crcZ expression. Here we have identified a conserved palindromic nucleotide sequence that is present in upstream activating sequences (UASs) of promoters under positive control by CbrB and σ(54) RNA polymerase, especially in the UAS of the crcZ promoter. Evidence for recognition of this palindromic sequence by CbrB was obtained in vivo from mutational analysis of the crcZ promoter and in vitro from electrophoretic mobility shift assays using crcZ promoter fragments and purified CbrB protein truncated at the N terminus. Integration host factor (IHF) was required for crcZ expression. CbrB also activated the lipA (lipase) promoter, albeit less effectively, apparently by interacting with a similar but less conserved palindromic sequence in the UAS of lipA. As expected, succinate caused CbrB-dependent catabolite repression of the lipA promoter. Based on these results and previously published data, a consensus CbrB recognition sequence is proposed. This sequence has similarity to the consensus NtrC recognition sequence, which is relevant for nitrogen control.

Etude épidémiologique inter-régionale suisse du risque de tumeur controlatérale du sein [Swiss interregional epidemiologic study of the risk of cancer in the contralateral breast].

This epidemiologic investigation in three Swiss regions (Geneva, St. Gall-Appenzell, Vaud) included 5,193 women diagnosed as having a first primary breast cancer. The patients were followed up for ten years (the observation totalled 24,994 women-years). Overall, these results confirmed that the relative risk of a second breast cancer was greatly increased during the first year following the primary diagnosis, but this was largely due to simultaneously discovered contralateral tumours. Beyond the first year of follow-up, the relative risk of a second tumour was lower but still significantly greater than unity. No significant diminution of the excess risk was observed in the first 10 years of follow-up. Relative risk of a second breast cancer was generally higher before age 50, independently of the latency. The relative risk of a second breast cancer differed significantly from one region to another, possibly due to specific techniques of registration.

Queen recruitment in a highly polygynous supercolony of formica-lugubris (Hymenoptera, Formicidae)

This work examines behavioural relationships between young females (potential queens) and workers, in a multi-nest population (supercolony), of Formica lugubris. Each nest contains hundreds of functional queens but the colony is initiated by a single foundress (secondary polygyny). Thus, recruitment of new queens into the nests is part of the population dynamics. Substantial variation in worker response towards introduced female sexuals, ranging from execution to complete acceptance, is demonstrated. The mating status of the introduced females has a clear effect on the worker response: virgin females are accepted with about twice the probability of inseminated females. When native alates are present in a nest, all introduced females are accepted with higher probability than when the native alates are absent, later in the season. No effect of distance (between donor and recipient nests) on the worker reaction was found, within the supercolony borders. Proximate mechanisms and selective forces regulating the recruitment process are discussed in light of these findings.

Estimating dormant and active hematopoietic stem cell kinetics through extensive modeling of bromodeoxyuridine label-retaining cell dynamics.

Bone marrow hematopoietic stem cells (HSCs) are responsible for both lifelong daily maintenance of all blood cells and for repair after cell loss. Until recently the cellular mechanisms by which HSCs accomplish these two very different tasks remained an open question. Biological evidence has now been found for the existence of two related mouse HSC populations. First, a dormant HSC (d-HSC) population which harbors the highest self-renewal potential of all blood cells but is only induced into active self-renewal in response to hematopoietic stress. And second, an active HSC (a-HSC) subset that by and large produces the progenitors and mature cells required for maintenance of day-to-day hematopoiesis. Here we present computational analyses further supporting the d-HSC concept through extensive modeling of experimental DNA label-retaining cell (LRC) data. Our conclusion that the presence of a slowly dividing subpopulation of HSCs is the most likely explanation (amongst the various possible causes including stochastic cellular variation) of the observed long term Bromodeoxyuridine (BrdU) retention, is confirmed by the deterministic and stochastic models presented here. Moreover, modeling both HSC BrdU uptake and dilution in three stages and careful treatment of the BrdU detection sensitivity permitted improved estimates of HSC turnover rates. This analysis predicts that d-HSCs cycle about once every 149-193 days and a-HSCs about once every 28-36 days. We further predict that, using LRC assays, a 75%-92.5% purification of d-HSCs can be achieved after 59-130 days of chase. Interestingly, the d-HSC proportion is now estimated to be around 30-45% of total HSCs - more than twice that of our previous estimate.

Characterization of hydroxyapatite laser ablation plumes by fast intensified CCD-imaging

ArF excimer laser pulses (193 nm, 20 ns, 150 mJ) have been focused on a hydroxyapatite (HA) target in similar conditions to those normally used for thin film deposition. Fast intensified CCD images of HA laser ablation plumes have been taken in vacuum and under different water vapor pressures ranging from 0.01 mbar to 1 mbar. Images of HA ablation in vacuum have shown a plume freely expanding at a constant velocity of 2.3 106 cm/s. HA ablation under a water vapor pressure of 0.01 mbar has revealed an expansion behavior very similar to that of ablation in vacuum. Images taken under a water vapor pressure of 0.1 mbar have shown the formation of a shock structure in the plume. Finally, HA ablation under a water vapor pressure of 1 mbar has revealed the development of some irregularities in the shape of the plume.

Ultraviolet optical and microstructural properties of MgF2 and LaF3 coatings deposited by ion-beam sputtering and boat and electron-beam evaporation

Single layers of MgF2 and LaF3 were deposited upon superpolished fused-silica and CaF2 substrates by ion-beam sputtering (IBS) as well as by boat and electron beam (e-beam) evaporation and were characterized by a variety of complementary analytical techniques. Besides undergoing photometric and ellipsometric inspection, the samples were investigated at 193 and 633 nm by an optical scatter measurement facility. The structural properties were assessed with atomic-force microscopy, x-ray diffraction, TEM techniques that involved conventional thinning methods for the layers. For measurement of mechanical stress in the coatings, special silicon substrates were coated and analyzed. The dispersion behavior of both deposition materials, which was determined on the basis of various independent photometric measurements and data reduction techniques, is in good agreement with that published in the literature and with the bulk properties of the materials. The refractive indices of the MgF2 coatings ranged from 1.415 to 1.440 for the wavelength of the ArF excimer laser (193 nm) and from 1.435 to 1.465 for the wavelength of the F2 excimer laser (157 nm). For single layers of LaF3 the refractive indices extended from 1.67 to 1.70 at 193 nm to ~1.80 at 157 nm. The IBS process achieves the best homogeneity and the lowest surface roughness values (close to 1 nmrms) of the processes compared in the joint experiment. In contrast to MgF2 boat and e-beam evaporated coatings, which exhibit tensile mechanical stress ranging from 300 to 400 MPa, IBS coatings exhibit high compressive stress of as much as 910 MPa. A similar tendency was found for coating stress in LaF3 single layers. Experimental results are discussed with respect to the microstructural and compositional properties as well as to the surface topography of the coatings.

Usefulness of heart rate to predict cardiac events in treated patients with high-risk systemic hypertension.

A high heart rate (HR) predicts future cardiovascular events. We explored the predictive value of HR in patients with high-risk hypertension and examined whether blood pressure reduction modifies this association. The participants were 15,193 patients with hypertension enrolled in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and followed up for 5 years. The HR was assessed from electrocardiographic recordings obtained annually throughout the study period. The primary end point was the interval to cardiac events. After adjustment for confounders, the hazard ratio of the composite cardiac primary end point for a 10-beats/min of the baseline HR increment was 1.16 (95% confidence interval 1.12 to 1.20). Compared to the lowest HR quintile, the adjusted hazard ratio in the highest quintile was 1.73 (95% confidence interval 1.46 to 2.04). Compared to the pooled lower quintiles of baseline HR, the annual incidence of primary end point in the top baseline quintile was greater in each of the 5 study years (all p <0.05). The adjusted hazard ratio for the primary end point in the highest in-trial HR heart rate quintile versus the lowest quintile was 1.53 (95% confidence interval 1.26 to 1.85). The incidence of primary end points in the highest in-trial HR group compared to the pooled 4 lower quintiles was 53% greater in patients with well-controlled blood pressure (p <0.001) and 34% greater in those with uncontrolled blood pressure (p = 0.002). In conclusion, an increased HR is a long-term predictor of cardiovascular events in patients with high-risk hypertension. This effect was not modified by good blood pressure control. It is not yet known whether a therapeutic reduction of HR would improve cardiovascular prognosis.