T cell responses to repeat and non-repeat regions of the circumsporozoite protein detected in volunteers immunized with Plasmodium falciparum sporozoites

The design of malarial vaccine based on the circumsporozoite (CS) protein, a majuor surface antigen of the sporozoite stage of the malaria parasite, requires the identification of T and B cell epitopes for inclusion in recombinant or synthetic vaccine candidates. We have investigated the specificity and function of a series of T cell clones, derived from volunteers immunized with Plasmodium falciparum sporozoites in an effort to identify relevant epitopes in the immune response to the pre-erythrocytic stages of the parasite. CD4+ T cell clones were obtained wich specifically recognized a repetitive epitope located in the 5'repeat region of the CS protein. This epitope, when conjugated to the 3'repeat region in a synthetic MAPs construct, induced high titers of antisporozoite antibodies in C57B1 mice. A second T cell epitope, which mapped to aa 326-345 of the carboxy terminal, was recognized by lytic, as well as non-lytic, CD4+ T cells derived from the sporozoite-immunized volunteers. The demonstration of CD4+ CTL in the volunteers, and the recent studies inthe rodent model (Renia et al., 1991; Tsuji et al., 1990), suggested that CS-specific CD4+ T cells, in addition to their indirect role as helper cells in the induction of antibody and CD8 + effector cells, may also play a direct role in protection against sporozoite challenge by targeting EEF within the liver.

Intravoxel incoherent motion perfusion imaging in acute stroke: initial clinical experience.

INTRODUCTION: Intravoxel incoherent motion (IVIM) imaging is an MRI perfusion technique that uses a diffusion-weighted sequence with multiple b values and a bi-compartmental signal model to measure the so-called pseudo-diffusion of blood caused by its passage through the microvascular network. The goal of the current study was to assess the feasibility of IVIM perfusion fraction imaging in patients with acute stroke. METHODS: Images were collected in 17 patients with acute stroke. Exclusion criteria were onset of symptoms to imaging >5 days, hemorrhagic transformation, infratentorial lesions, small lesions <0.5 cm in minimal diameter and hemodynamic instability. IVIM imaging was performed at 3 T, using a standard spin-echo Stejskal-Tanner pulsed gradients diffusion-weighted sequence, using 16 b values from 0 to 900 s/mm(2). Image quality was assessed by two radiologists, and quantitative analysis was performed in regions of interest placed in the stroke area, defined by thresholding the apparent diffusion coefficient maps, as well as in the contralateral region. RESULTS: IVIM perfusion fraction maps showed an area of decreased perfusion fraction f in the region of decreased apparent diffusion coefficient. Quantitative analysis showed a statistically significant decrease in both IVIM perfusion fraction f (0.026 ± 0.019 vs. 0.056 ± 0.025, p = 2.2 · 10(-6)) and diffusion coefficient D compared with the contralateral side (3.9 ± 0.79 · 10(-4) vs. 7.5 ± 0.86 · 10(-4) mm(2)/s, p = 1.3 · 10(-20)). CONCLUSION: IVIM perfusion fraction imaging is feasible in acute stroke. IVIM perfusion fraction is significantly reduced in the visible infarct. Further studies should evaluate the potential for IVIM to predict clinical outcome and treatment response.

The serological differentiation of acute and chronic schistosomiasis japonica using IgA antibody to egg antigen

Two groups of Schistosoma japonicum infected patients (acute and chronic ) and non-infected individuals were studied using IgA antibody to egg antigen (SEA) and IgG and IgM antibodies to keyhole limpet haemocyanin (KLH). The means and standard deviation of the optical density in ELISA of acute, chronic and negative groups for IgA anti-SEA were 583±124.7, 98.2±78.8 and 82.2±39. 3, respectively. There was a statistically significance between acute patients and chronic patients (P<0.01). The means and standard deviation of IgG and IgM antibodies to KLH were 501.5±150.6, 113.0±79.1, 28.8±56.3 and 413.6±148.5, 70.2±14.8, 65.3±45.3, respectively. The detection results of IgA to SEA compared with the IgG and IgM to KLH did not demonstrate a significant difference (P>0.01). The sensitivities of IgA to SEA and IgG and IgM antibodies to KLH for the detection of acute infection were 95.24%, 90.48% and 85.71%, respectively. Therefore, this study showed that the detection of IgA to SEA is also a useful new method for the serological differentiation of acute and chronic schistosomiasis japonica in humans.

Lu pour vous: Augmenter l'activité physique chez l'enfant: rien ne sert de faire courir ?

Résumé de: Metcalf B, et al. Effectiveness of intervention on physical activity of children: systematic review and meta-analysis of controlled trials with objectively measured outcomes (EarlyBird 54). BMJ. 2012 Sep 27;345:e5888. doi: 10.1136/bmj.e5888. PMID: 23044984.

Visceral leishmaniasis in the Metropolitan Region of Belo Horizonte, State of Minas Gerais, Brazil

In the last few years the number of human cases of American visceral leishmaniasis in the Metropolitan Region of Belo Horizonte (MRBH), Minas Gerais, Brazil has increased, indicating an elevation in the transmission rate of the disease. The total number of notified human cases in the MRBH since 1994, when the first case was identified, up to 1999 was 345 of which 223 (65%) were from the city itself, indicating an urbanization of the disease in this region of Minas Gerais. The age distribution of visceral leishmaniasis cases in the MRBH shows a higher prevalence in children from 0-4 years old, responsible for 28.9% of the notifications. Clinical and immunological findings from dogs infected with Leishmania chagasi are described. The majority of these animals showed no sign of the disease. Sera from all infected dogs showed detectable Leishmania-induced high titles of antibodies based on the results of an indirect fluorescent antibody test. Samples of isolated Leishmania from human and dogs were characterized as L. (L.) chagasi by biochemical and molecular techniques.

How Low Can We Go in Contrast-Enhanced CT Imaging of the Chest?: A Dose-Finding Cadaver Study Using the Model-based Iterative Image Reconstruction Approach.

RATIONALE AND OBJECTIVES: Dose reduction may compromise patients because of a decrease of image quality. Therefore, the amount of dose savings in new dose-reduction techniques needs to be thoroughly assessed. To avoid repeated studies in one patient, chest computed tomography (CT) scans with different dose levels were performed in corpses comparing model-based iterative reconstruction (MBIR) as a tool to enhance image quality with current standard full-dose imaging. MATERIALS AND METHODS: Twenty-five human cadavers were scanned (CT HD750) after contrast medium injection at different, decreasing dose levels D0-D5 and respectively reconstructed with MBIR. The data at full-dose level, D0, have been additionally reconstructed with standard adaptive statistical iterative reconstruction (ASIR), which represented the full-dose baseline reference (FDBR). Two radiologists independently compared image quality (IQ) in 3-mm multiplanar reformations for soft-tissue evaluation of D0-D5 to FDBR (-2, diagnostically inferior; -1, inferior; 0, equal; +1, superior; and +2, diagnostically superior). For statistical analysis, the intraclass correlation coefficient (ICC) and the Wilcoxon test were used. RESULTS: Mean CT dose index values (mGy) were as follows: D0/FDBR = 10.1 ± 1.7, D1 = 6.2 ± 2.8, D2 = 5.7 ± 2.7, D3 = 3.5 ± 1.9, D4 = 1.8 ± 1.0, and D5 = 0.9 ± 0.5. Mean IQ ratings were as follows: D0 = +1.8 ± 0.2, D1 = +1.5 ± 0.3, D2 = +1.1 ± 0.3, D3 = +0.7 ± 0.5, D4 = +0.1 ± 0.5, and D5 = -1.2 ± 0.5. All values demonstrated a significant difference to baseline (P < .05), except mean IQ for D4 (P = .61). ICC was 0.91. CONCLUSIONS: Compared to ASIR, MBIR allowed for a significant dose reduction of 82% without impairment of IQ. This resulted in a calculated mean effective dose below 1 mSv.

Production of recombinant TRAIL and TRAIL receptor: Fc chimeric proteins.

The tumor necrosis factor (TNF)/TNF receptor (TNFR) families of ligands and receptors are implicated in a variety of physiological and pathological processes and regulate cellular functions as diverse as proliferation, differentiation, and death. Recombinant forms of these ligands and receptors can act to agonize or antagonize these functions and are therefore useful for laboratory studies and may have clinical applications. A protocol is presented for the expression and purification of dimeric soluble receptors fused to the Fc portion of human IgG1 and of soluble, N-terminally Flag-tagged ligands. Soluble recombinant proteins are easier to handle than membrane-bound proteins and the use of tags greatly facilitates their detection and purification. In addition, some tags may provide enhanced biological activity to the recombinant proteins (mainly by oligomerization and stabilization effects) and facilitate their functional characterization. Expression in bacterial (for selected ligands) and eukaryotic expression systems (for ligands and receptors) was performed using M15 pREP4 bacteria and human embryonic kidney 293 cells, respectively. The yield of purified protein is about 1 mg/liter for the mammalian expression system and several milligrams per liter for the bacterial expression system. Protocols are given for a specific ligand-receptor pair, namely TRAIL (Apo-2L) and TRAIL receptor 2 (DR5), but can be applied to other ligands and receptors of the TNF family.

Characterisation of the prodrome to a first episode of psychotic mania: results of a retrospective study.

BACKGROUND: Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative "high-risk" studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a sub-group of at-risk subjects. METHODS: Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses. RESULTS: Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are however likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample, may be an indicator of impending first episode mania. LIMITATIONS: This is a retrospective study, in a small sample of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies. CONCLUSIONS: Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD could be a sign of impending first episode mania.

The feasibility of 350 μm spatial resolution coronary magnetic resonance angiography at 3 T in humans.

PURPOSE: The purposes of this study were to (1) develop a high-resolution 3-T magnetic resonance angiography (MRA) technique with an in-plane resolution approximate to that of multidetector coronary computed tomography (MDCT) and a voxel size of 0.35 × 0.35 × 1.5 mm³ and to (2) investigate the image quality of this technique in healthy participants and preliminarily in patients with known coronary artery disease (CAD). MATERIALS AND METHODS: A 3-T coronary MRA technique optimized for an image acquisition voxel as small as 0.35 × 0.35 × 1.5 mm³ (high-resolution coronary MRA [HRC]) was implemented and the coronary arteries of 22 participants were imaged. These included 11 healthy participants (average age, 28.5 years; 5 men) and 11 participants with CAD (average age, 52.9 years; 5 women) as identified on MDCT. In addition, the 11 healthy participants were imaged using a method with a more common spatial resolution of 0.7 × 1 × 3 mm³ (regular-resolution coronary MRA [RRC]). Qualitative and quantitative comparisons were made between the 2 MRA techniques. RESULTS: Normal vessels and CAD lesions were successfully depicted at 350 × 350 μm² in-plane resolution with adequate signal-to-noise ratio (SNR) and contrast-to-noise ratio. The CAD findings were consistent among MDCT and HRC. The HRC showed a 47% improvement in sharpness despite a reduction in SNR (by 72%) and in contrast-to-noise ratio (by 86%) compared with the regular-resolution coronary MRA. CONCLUSION: This study, as a first step toward substantial improvement in the resolution of coronary MRA, demonstrates the feasibility of obtaining at 3 T a spatial resolution that approximates that of MDCT. The acquisition in-plane pixel dimensions are as small as 350 × 350 μm² with a 1.5-mm slice thickness. Although SNR is lower, the images have improved sharpness, resulting in image quality that allows qualitative identification of disease sites on MRA consistent with MDCT.