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Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders resulting from multiple factors. Diagnosis is based on behavioural and developmental signs detected before 3 years of age, and there is no reliable biological marker. The purpose of this study was to evaluate the value of gas chromatography combined with mass spectroscopy (GC-MS) associated with multivariate statistical modeling to capture the global biochemical signature of autistic individuals. GC-MS urinary metabolic profiles of 26 autistic and 24 healthy children were obtained by liq/liq extraction, and were or were not subjected to an oximation step, and then were subjected to a persilylation step. These metabolic profiles were then processed by multivariate analysis, in particular orthogonal partial least-squares discriminant analysis (OPLS-DA, RY(cum) = 0.97, Q(cum) = 0.88). Discriminating metabolites were identified. The relative concentrations of the succinate and glycolate were higher for autistic than healthy children, whereas those of hippurate, 3-hydroxyphenylacetate, vanillylhydracrylate, 3-hydroxyhippurate, 4-hydroxyphenyl-2-hydroxyacetate, 1 H-indole-3-acetate, phosphate, palmitate, stearate, and 3-methyladipate were lower. Eight other metabolites, which were not identified but characterized by a retention time plus a quantifier and its qualifier ion masses, were found to differ between the two groups. Comparison of statistical models leads to the conclusion that the combination of data obtained from both derivatization techniques leads to the model best discriminating between autistic and healthy groups of children. [ABSTRACT FROM AUTHOR]

In order to investigate the influence of inflammation on the peripheral glycosylation of airway mucins, a human respiratory glandular cell line (MM-39) was treated by TNFα. The expression and the activity of sialyl- and fucosyl-transferases, involved in the biosynthesis of peripheral carbohydrate determinants like sialyl-Lewis x, were investigated by RT-PCR and by HPAEC respectively. The mRNA steady-state level of sialyl- (ST3Gal III) and of fucosyl- (FUT3) transferases was moderately up-regulated by TNFα; a 52% increase of α2,3-sialyltransferase activity was also observed in TNFα-stimulated MM-39 cells. After metabolic radio-labelling with [3H]glucosamine and [3H]fucose, the mucins released in␣the culture supernatant were purified by Sepharose CL-4B, density-gradient centrifugation and treatment with glycosaminoglycans-degrading enzymes. The mucins, released in the culture supernatant from control MM-39 cells, were constituted by two populations of molecules having the same 1.39–1.44 mg/ml density but carrying either high or low amounts of sialic acid residues at their periphery. TNFα was able to increase the sialylation of the weakly sialylated mucins. This effect and the enhancement of the α2,3-sialyltransferase activity by TNFα argue in favour of a regulation of the mucin sialylation by this pro-inflammatory cytokine. Despite the moderate overexpression of FUT3, no fucosylation of mucins produced by MM-39 cells was induced by TNFα. In conclusion, the influence of TNFα on the sialylation of mucins could explain why the mucins from infected patients suffering either from cystic fibrosis or from chronic bronchitis are more sialylated. [ABSTRACT FROM AUTHOR]

We previously demonstrated that two human pancreatic adenocarcinoma cell lines, CFPAC-1 (established from a patient with cystic fibrosis) and CAPAN-1, were able to secrete trypsinogens 1 and 2 specifically. In order to analyze the relation of trypsin secretion to differentiation and cell growth, we undertook a comparative study of immunoreactive trypsin 1 (IRT) secretion by the two cell lines during cell growth in the presence and in the absence of various differentiating agents: sodium butyrate (NaBut), dimethylsulfoxide (DMSO), and dexamethasone (DX). In the presence of NaBut, IRT levels in the supernatants of both cell lines were slightly increased, whereas the cellular growth of both cell lines decreased significantly. In the presence of DX, IRT levels in cell culture conditioned media immediately and dramatically decreased, but the cell growth of neither cell line was affected by DX. An important increase in IRT levels was observed when CFPAC-1 cells and CAPAN-1 cells were grown in the presence of DMSO, but for both cell lines the cellular growth decreased in the presence of DMSO. Our data show that neither the IRT secretion level nor the differentiation state of these cell lines correlates with cellular growth, and suggests that the expression of pancreatic proteases by these two tumor cell lines could be either related to a common stem cell with this potential or to a possible acinar origin of pancreatic cancer, as recently proposed by others. [ABSTRACT FROM AUTHOR]