DTPA and anti-inflammatory drug associations to alleviate Pu-induced response of macrophages in vitro.

Internal contamination by inhalation of plutonium poorly soluble compounds leads to their long time retention in alveolar macrophages inducing delayed pathology development. As previous studies highlighted co-localization of retained Pu and inflammatory lesions, this study was designed to assess the combined effect of the reference treatment (DTPA) and anti-inflammatory drugs on Pu-induced early response of macrophages in vitro. Pu colloids, mimicking poorly soluble Pu, were characterized using filtration and solid-state nuclear track detectors CR39.

Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype.

Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in SMARCA2, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of ADNP present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS).

Phenotypic and genotypic characterization of 1q21.1 copy number variants: A report of 34 new individuals and literature review.

Recurrent 1q21.1 copy number variants (CNVs) have been associated with a wide spectrum of clinical features, ranging from normal phenotype to moderate intellectual disability, with congenital anomalies and dysmorphic features. They are often inherited from unaffected parents and the pathogenicity is difficult to assess.

Critical Review on Toxicological Mechanisms Triggered by Inhalation of Alumina Nanoparticles on to the Lungs.

Alumina nanoparticles (AlO NPs) can be released in occupational environments in different contexts such as industry, defense, and aerospace. Workers can be exposed by inhalation to these NPs, for instance, through welding fumes or aerosolized propellant combustion residues. Several clinical and epidemiological studies have reported that inhalation of AlO NPs could trigger aluminosis, inflammation in the lung parenchyma, respiratory symptoms such as cough or shortness of breath, and probably long-term pulmonary fibrosis.

Nose-only inhalations of high-dose alumina nanoparticles/hydrogen chloride gas mixtures induce strong pulmonary pro-inflammatory response: a pilot study.

Objective: Solid composite propellants combustion, in aerospace and defense fields, can lead to complex aerosols emission containing high concentrations of alumina nanoparticles (AlO NPs) and hydrogen chloride gas (HCl). Exposure to these mixtures by inhalation is thus possible but literature data toward their pulmonary toxicity are missing. To specify hazards resulting from these combustion aerosols, a pilot study was implemented.

HIST1H1E heterozygous protein-truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals.

Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome.

Alumina nanoparticles size and crystalline phase impact on cytotoxic effect on alveolar epithelial cells after simple or HCl combined exposures.

Applications using alumina nanoparticles (AlO NPs) have incredibly increased in different fields of activity. In defense and aerospace fields, solid composite propellants use leads to complex combustion aerosols emissions containing high concentrations of AlO NPs and hydrogen chloride gas (HCl). To better characterize potential hazard resulting from exposure to these aerosols, this study assesses cytotoxic effects of mixtures containing both compounds on human pulmonary alveolar epithelial cells (A549 cell line) after 24 h exposures.

Biodistribution of adult derived human liver stem cells following intraportal infusion in a 17-year-old patient with glycogenosis type 1A.

Introduction: Current treatment of inherited liver inborn errors of metabolism in children consists in appropriate diet and drugs and, for unstable patients, final orthotopic liver transplantation. Unfortunately, liver transplantation remains not easily available because of organ shortage and imposes inherent risks and lifelong immunosuppressive therapy. Therefore alternative treatments are required.

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in children and adolescents.

Background & Aims: This multi-center study aimed to prospectively evaluate the safety and efficacy of a genotype-based Pegylated Interferon alfa-2a/Ribavirin therapy in treatment-naïve hepatitis C virus (HCV), positive HCV serology, and quantifiable HCV RNA, infected children.

Methods: Eighteen children with genotypes 2 and 3 patients (group A) were assigned to medication for 24weeks, and 47 children with genotypes 1, 4, 5 and 6 patients (group B) for 48weeks.

Results: Early response at week 12 was observed in 83% of group A patients and in 57% of group B patients (p<0.

Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives.

Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma.

Randomised revaccination with pneumococcal polysaccharide or conjugate vaccine in asplenic children previously vaccinated with polysaccharide vaccine.

Objective: Asplenic children are at high risk of invasive pneumococcal infection. In this group, the American Academy of Pediatrics recommends a single revaccination with the 23-valent polysaccharide vaccine (PSV23) 3-5 years after a previous PSV23 dose. Despite potential advantages, there are few data available regarding the safety and immunogenicity of the heptavalent pneumococcal conjugate vaccine (PCV7) in this population.

Chronic hepatitis B infection: long term comparison of children receiving interferon alpha and untreated controls.

Objectives: To investigate the virological outcome of chronic hepatitis B (CH-B) in children who received interferon alpha (IFN) compared with no treatment.

Methods: Seventy-four children with CH-B (median age, 6.1 years; 44 boys) selected from a cohort of 158 cases were included and divided into two groups: IFN-treated (n = 37) and control (n = 37).

Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up.

Hepatocyte transplantation is an investigational alternative to orthotopic liver transplantation to treat liver based inborn errors of metabolism. We report successful hepatocyte transplantation in a 4-year-old girl with infantile Refsum disease. Hepatocytes were isolated from the left liver segment of two male donors using a classic two-step perfusion method.

Induction of a protection against S. mansoni with a MAP containing epitopes of Sm37-GAPDH and Sm10-DLC. Effect of coadsorption with GM-CSF on alum.

Studies of anti-S. mansoni immunological responses in individuals living in endemic areas identified immunogens (Sm37-GAPDH and Sm10-DLC) with vaccine candidate properties. Analysis of the epitopes of these immunogens indicated that: (i) Sm37-5 is a major B-cell epitope of Sm37-GAPDH and the IgG antibody reactivity toward this determinant is associated with resistance to reinfection; (ii) Sm10-T is a T-cell epitope of the major T-cell immunogen Sm10-DLC.

Production of Sm37-GAPDH, a major therapeutical target in human schistosomiasis.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in the glycolytic metabolism and the production of energy. This probably explains why GAPDH was evidenced as a major therapeutical target in several parasitic diseases; either as a vaccine candidate or as a target for chemotherapeutic treatments. Schistosoma mansoni GAPDH (Sm37-GAPDH) is one of the main schistosome vaccine candidates.

Identification of a candidate vaccine peptide on the 37 kDa Schistosoma mansoni GAPDH.

A previous study performed in adolescents living in an area endemic for Schistosoma mansoni in Brazil has shown that a 37 kDa schistosome surface antigen is a selective target for antibodies in sera from those who were resistant to reinfection. This antigen was shown by molecular cloning to be the schistosome GAPDH. The aim of the present work was to assess whether peptides corresponding to GAPDH antigenic determinants could be used in a subunit vaccine.

Induction of a protective immunity against Schistosoma mansoni with ovalbumin-coupled Sm37-5 coadsorbed with granulocyte-macrophage colony stimulating factor (GM-CSF) or IL-12 on alum.

A previous study has shown that Sm37-5 is a major B cell epitope of Sm37-GAPDH. This epitope is highly antigenic in human infections and IgG antibody reactivity toward this determinant is associated with adolescent resistance to reinfection. This led us to test a synthetic peptide corresponding to Sm37-5, coupled to ovalbumin, as an anti-schistosome vaccine.

Characterization of a schistosome T cell-stimulating antigen (Sm10) associated with protective immunity in humans.

Parasite antigens that are strong T cell immunogens represent potential candidates for vaccines against pathogens susceptible to T cell-mediated immunity. We have previously shown that chromatographic fractions of schistosomula extracts contain components that are major T cell immunogen(s) in natural schistosome infections in humans and might contribute to the induction of human protective immunity against this parasite. In the present study, we report on the molecular cloning and on the biochemical characterization of the active components of these fractions.

Identification of a major T cell immunogen in the anti-schistosome response of adult residents in an area endemic for Schistosoma mansoni.

Vaccine-induced immunity to Schistosoma mansoni infection depends on the specific priming of certain T cell subsets and on the recall of this response by natural infections months or years after vaccine administration. Thus, those schistosome proteins that activate T cells in individuals stimulated by natural infections are potential candidate vaccine antigens. In the present study, we identified and purified one such T cell-stimulating antigen and evaluated its immunological properties in subjects living in an area endemic for Schistosoma mansoni.

Resistance to Schistosoma mansoni in humans: influence of the IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy.

The hypothesis of an association between human resistance to reinfection by the parasite Schistosoma mansoni and anti-larval immunoglobulin isotypes was tested by logistic regression in the presence of the explicative variables water contact, age, and sex. Of the seven isotypes tested (IgM, IgG1, IgG2, IgG3, IgG4, IgA, and IgE), only IgE, IgG4, and IgG2 showed an association (positive for IgE and negative for IgG2 and IgG4) with resistance to reinfection after chemotherapy. The opposite effects of IgE and IgG4 were undissociable in the analysis, indicating that these isotypes probably antagonize each other in protection.

Strong serum inhibition of specific IgE correlated to competing IgG4, revealed by a new methodology in subjects from a S. mansoni endemic area.

A method allowing the immunopurification of human IgE from small volumes of sera with a yield close to 100% (mean = 97.8%; SEM = 0.7) has been developed.

Environmental, genetic and immunological factors in human resistance to Schistosoma mansoni.

The design of programs for the control of endemies requires the knowledge of the principal factors that determine parasite transmission and infection levels in exposed populations. In the studies summarized in this article, the role of environmental and host specific factors in the infection by S. mansoni have been evaluated.

Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels.

The anti-larval IgE antibody response of adolescents with high or low resistance to infection by Schistosoma mansoni was evaluated before parasitological cure with oxamniquine and over an extended post-treatment period during which the least resistant subjects regained high infections. IgE from most sera, taken at several bleeding times before and after treatment, reacted, on immunoblots, with a large number of antigens (Ag) in schistosomular tegument extract. A family of 120-165-kDa cross-reacting molecules and a 85-kDa Ag were the most prominent Ag.

Immunological analysis of porin polymorphism in Escherichia coli B and K-12.

Two sets of monoclonal antibodies (MoF type I and MoF type II) directed against the OmpF protein were used to analyze the immunological reactivity of the major outer membrane porins of E. coli B and K-12. All these antibodies present a specificity to the native OmpF protein.