Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems

C4B null alleles are not associated with genetic polymorphisms in the adjacent gene CYP21A2 in autism

<p>Abstract</p> <p>Background</p> <p>Research indicates that the etiology of autism has a strong genetic component, yet so far the search for genes that contribute to the disorder, including several whole genome scans, has led to few consistent findings. However, three studies indicate that the complement <it>C4B </it>gene null allele (i.e. the missing or nonfunctional <it>C4B </it>gene) is significantly more frequent in individuals with autism. Due to the close proximity of the <it>CYP21A2 </it>gene to the <it>C4B </it>locus (3 kb) it was decided to examine samples from autistic subjects, including many with known <it>C4B </it>null alleles for common <it>CYP21A2 </it>mutations.</p> <p>Methods</p> <p>Samples from subjects diagnosed with autism and non-autistic controls (controls) previously typed for <it>C4B </it>null alleles were studied. Allele specific polymerase chain reaction (PCR) methods were used to determine 8 of the most common <it>CYP21A2 </it>genetic mutations, known to completely or partially inhibit 21-hydroxylase, the enzyme encoded by the <it>CYP21A2 </it>gene.</p> <p>Results</p> <p>Although the combined autism and control study subjects had 50 <it>C4B </it>null alleles only 15 <it>CYP21A2 </it>mutations were detected in over 2250 genotypes. Eight mutations were detected in the autistic samples and 7 in the controls. The frequency of <it>CYP21A2 </it>mutations was similar between the autism and control samples. Only one individual (autistic) carried a chromosome containing both <it>C4B </it>null allele and <it>CYP21A2 </it>mutations.</p

Human Flt3L Generates Dendritic Cells from Canine Peripheral Blood Precursors: Implications for a Dog Glioma Clinical Trial

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads) encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L) and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK). This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs), in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF.Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-alpha and IFN-gamma. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation.These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials