Specific isotype immune response in the diagnosis of human schistosomiasis pathology?

Since the few indirect markers available for assessing the development and the stage of intestinal schistosomiasis morbidity are weakly specific, endoscopy is still the only method able to detect severe forms of pathology. Therefore, we evaluated the isotype antibody response to the current schistosome antigen preparation (soluble egg antigens [SEA]) in 142 Senegalese patients infected with Schistosoma mansoni. They were stratified into three different stages of pathology according to ultrasonographic, endoscopic, and clinical parameters (stage 1 = no detectable pathology; stage 2 = moderate morbidity; stage 3 = severe forms of pathology). Only median specific IgG4, IgE, and IgA responses changed according to the stage of pathology. The IgA level was significantly higher in stages 2 and 3 compared with stage 1, and the IgE level was higher in stage 3 compared with stage 1. A high specific IgG4 level was observed only in stage 3 and was significantly different compared with stage 2. We show an association between the variability of the specific response to SEA and the degree of morbidity, and demonstrate that IgA and IgG4 responses could be combined markers to easily discriminate the different stages of pathology due to infection with S. mansoni.     

Bichat guidelines for the clinical management of viral encephalitis and bioterrorism-related viral encephalitis

Most of the viruses involved in causing encephalitis are arthropod-borne viruses, with the exception of arenaviruses that are rodent-borne. Even if little information is available, there are indications that, most of these encephalitis-associated viruses could be used by aerosolisation during a bioterrorist attack. Viral transfer from blood to the CNS through the olfactory tract has been suggested. Another possible route of contamination is by vector-borne transmission such as infected mosquitoes or ticks. Alphaviruses are the most likely candidates for weaponisation. The clinical course of the diseases caused by these viruses is usually not specific, but differentiation is possible by using an adequate diagnostic tool. There is no effective drug therapy for the treatment of these diseases and treatment is mainly supportive, but vaccines protecting against some of these viruses do exist.     

Peripheral lymphocytes changes in the anamnestic response to tetanus toxoid challenge.

Few data are available on the blood lymphocyte response to revaccination in man. The anamnestic response to tetanus toxoid challenge was evaluated by a variety of techniques during the first week after revaccination. Out of twenty subjects used, eight were evaluated before and 5 days after the injections (days 1--8). Analytical cell electrophoresis showed important variation in the B and two T lymphocyte populations. The B cell percentages, assessed by EAC-rosettes and electrophoretic mobility, were found to decrease by days 2 and 3, and return to former levels by day 8, when a rise in specific antibodies was detected. A similar response was found in the T1 population generally considered to be composed of low affinity E-rosette-forming cells. Conversely, a significant increase (50--100%) in circulating T2 lymphocytes (active rosette-forming cells) was found by days 2 and 3, followed by a rapid decrease of these 'differenciated' cells. The increase in the T2 lymphocytes appeared earlier in skin test positive subjects. These changes were correlated with E-rosettes, mitogen stimulation, peripheral leucocyte migration inhibition and transformation in the presence of the antigen. EA-IgG rosettes and ADCC varied similarly. These results may indicate a significant non-specific cell mobilization following revaccination.     

Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus

In the absence of an effective vaccine, there is an urgent need for safe and effective antiviral agents to prevent transmission of HIV. Here, we report that an amphipathic alpha-helical peptide derived from the hepatitis C virus NS5A anchor domain (designated C5A in this article) that has been shown to be virocidal for the hepatitis C virus (HCV) also has potent antiviral activity against HIV. C5A exhibits a broad range of antiviral activity against HIV isolates, and it prevents infection of the three in vivo targets of HIV: CD4(+) T lymphocytes, macrophages, and dendritic cells by disrupting the integrity of the viral membrane and capsid core while preserving the integrity of host membranes. C5A can interrupt an ongoing T cell infection, and it can prevent transmigration of HIV through primary genital epithelial cells, infection of mucosal target cells and transfer from dendritic cells to T cells ex vivo, justifying future experiments to determine whether C5A can prevent HIV transmission in vivo.     

Unusual association of a unique CAG interruption in 5′ of DM1 CTG repeats with intergenerational contractions and low somatic mosaicism

Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder associated with high variability of symptoms and anticipation. DM1 is caused by an unstable CTG repeat expansion that usually increases in successive generations and tissues. DM1 family pedigrees have shown that ～90% and 10% of transmissions result in expansions and contractions of the CTG repeat, respectively. To date, the mechanisms of CTG repeat contraction remain poorly documented in DM1. In this report, we identified two new DM1 families with apparent contractions and no worsening of DM1 symptoms in two and three successive maternal transmissions. A new and unique CAG interruption was found in 5′ of the CTG expansion in one family, whereas multiple 5′ CCG interruptions were detected in the second family. We showed that these interruptions are associated with maternal intergenerational contractions and low somatic mosaicism in blood. By specific triplet‐prime PCR, we observed that CTG repeat changes (contractions/expansions) occur preferentially in 3′ of the interruptions for both families.     

The impact of sleep deprivation on visual perspective taking

Total sleep deprivation (TSD) is known to alter cognitive processes. Surprisingly little attention has been paid to its impact on social cognition. Here, we investigated whether TSD alters levels‐1 and ‐2 visual perspective‐taking abilities, i.e. the capacity to infer (a) what can be seen and (b) how it is seen from another person's visual perspective, respectively. Participants completed levels‐1 and ‐2 visual perspective‐taking tasks after a night of sleep and after a night of TSD. In these tasks, participants had to take their own (self trials) or someone else's (other trials) visual perspective in trials where both perspectives were either the same (consistent trials) or different (inconsistent trials). An instruction preceding each trial indicated the perspective to take (i.e. the relevant perspective). Results show that TSD globally deteriorates social performance. In the level‐1 task, TSD affects the selection of relevant over irrelevant perspectives. In the level‐2 task, the effect of TSD cannot be unequivocally explained. This implies that visual perspective taking should be viewed as partially state‐dependent, rather than a wholly static trait‐like characteristic.     

Whole MYBPC3 NGS sequencing as a molecular strategy to improve the efficiency of molecular diagnosis of patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, historically believed to affect 1 of 500 people. MYBPC3 pathogenic variations are the most frequent cause of familial HCM and more than 90% of them introduce a premature termination codon. The current study aims to determine the prevalence of deep intronic MYBPC3 pathogenic variations that could lead to splice mutations. To improve molecular diagnosis, a next‐generation sequencing (NGS) workflow based on whole MYBPC3 sequencing of a cohort of 93 HCM patients, for whom no putatively causative point mutations were identified after NGS sequencing of a panel of 48 cardiomyopathy‐causing genes, was performed. Our approach led us to reconsider the molecular diagnosis of six patients of the cohort (6.5%). These HCM probands were carriers of either a new large MYBPC3 rearrangement or splice intronic variations (five cases). Four pathogenic intronic variations, including three novel ones, were detected. Among them, the prevalence of one of them (NM_000256.3:c.1927+ 600 C>T) was estimated at about 0.35% by the screening of 1,040 unrelated HCM individuals. This study suggests that deep MYBPC3 splice mutations account for a significant proportion of HCM cases (6.5% of this cohort). Consequently, NGS sequencing of MYBPC3 intronic sequences have to be performed systematically.