Analyse discriminante de la sévérité de l'allergie à l'arachide

International audienceL'allergie à l'arachide est un problème de santé publique. La sévérité des réactions, parfois très graves, est évaluée par un score lors d'un Test de Provocation Orale (TPO), qui nécessite l'hospitalisation du patient, souvent un enfant, et peut s'avérer dangereux. Afin de s'en affranchir, ont été réalisées des analyses discriminantes concernant trois mesures de la sévérité de l'allergie à l'arachide : le score du TPO, la dose réactogène et le score de sévérité du premier accident, à partir de 2 groupes de variables explicatives par patient ($n=93$) : 6 dosages immunologiques et 30 tests cutanés. Une Analyse Factorielle Multiple a été implémentée afin d'équilibrer l'influence des deux groupes de variables sur les modèles prédictifs, avec les règles de classement linéaire et quadratique, les $k$-NN, CART, et AdaBoost, précédés par une phase de sélection de variables et testés par validation croisée. De plus, un algorithme permettant simultanément de regrouper les doses réactogènes en classes et de sélectionner les caractères discriminants est proposé

Fat emulsions are more than energy suppliers

The type of triglycerides in exogenous fat emulsions as well as the phospholipids: triglyceride ratio influences the plasma clearance. The plasma clearance cannot be used for indicating the utilization of fat emulsions as energy substrate. Introducing exogenous fat in replacement of part of the calories provided by glucose reduces a series of complications associated with large glucose intake. There are exchanges of triglycerides, esterified cholesterol, phospholipids and apoproteins between exogenous lipids and endogenous lipoproteins, depending on the composition of exogenous lipid emulsions. These interactions can significantly modify the composition of both, exogenous particles and endogenous lipoproteins. In future it will become essential to determine the removal site of 'exogenous remnants'. Future progress will allow a better understanding of the influence of these modifications on the metabolism of endogenous lipoproteins and the utilization of exogenous fat emulsions.SCOPUS: re.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Infidélité de transcription et carcinogénèse. Analyse bioinformatique et preuves de concept biologiques

L un des enjeux de la lutte contre le cancer réside dans la compréhension de l hétérogénéité de la maladie. Le but de notre travail a été d explorer l hétérogénéité des cellules cancéreuses du point de vue de la séquence d ARN messager. Les ESTs (ou Expressed Sequence Tags) d origine humaine ont été alignées aux séquences de référence ARNm. Les alignements ont été exploités de manière à mesurer les variations de séquence des ESTs issues de tissus tumoraux ou non tumoraux à chaque position de chaque transcrit. L analyse statistique mise en place a consisté à identifier les positions pour lesquelles les variations de séquence, i.e. substitutions, insertions et délétions, sont différentes entre les ESTs d origine tumorale et les ESTs d origine non tumorale. L étude bioinformatique s est d abord concentrée sur 17 transcrits abondamment exprimés avant d être étendue à l ensemble du transcriptome. Elle a ensuite été réalisée sur les ESTs murines. Les résultats montrent que l hétérogénéité des transcrits cancéreux est plus grande que celle des tissus sains. Ainsi, l infidélité de transcription est augmentée au cours de la carcinogénèse. Ce résultat bioinformatique a été validé par différentes approches biologiques. Tout d abord, le clonage puis le séquençage d un ARN provenant d une tumeur pulmonaire humaine et présentant une délétion prédite de manière bioinformatique ont été réalisés, et ce, en l absence de mutation somatique. Ensuite, l identification par spectrométrie de masse d un variant protéique issu de la traduction d un ARN dont le codon stop est substitué en triplet codant a été possible. Enfin, l intérêt de rechercher dans le sérum de patients cancéreux la présence d anticorps dirigés contre des protéines issues de la traduction d ARNm infidèles a été démontré. Ainsi, l infidélité de transcription est un phénomène augmenté dans le cancer et responsable d une partie de l hétérogénéité des cellules cancéreuses. L intérêt de cette découverte réside dans les perspectives nouvelles qu elle offre en termes de compréhension des mécanismes de carcinogénèse et en termes de diagnostic de la maladieOne of the aim of the fight against cancer is to understand the heterogeneity of cancer cells. The goal of our work has been to explore cancer cell mRNA heterogeneity. ESTs (Expressed Sequence Tags) extracted from normal and cancer tissues have been aligned to mRNA reference sequences. This allowed identification of non-random sequence variations that occurred at statistically significant increased rates in cancer compared to normal libraries. This analysis first focused on 17 abundant transcripts and was next extended to whole human genome, as well as to that of Mus musculus. The results show an increase of transcription infidelity events in cancer tissues. Three types of events occur, i.e. base substitutions, deletions and insertions. Bioinformatics results have been validated through different biological methods. First, the cloning and sequencing of mRNA from lung cancer human with a deletion occurring at bioinformatically predicted position in absence of somatic mutation has been achieved. Then, mass spectrometry analysis confirmed the existence of protein variants resulting from translation of mRNA bypassing stop codon. Finally, we showed that transcription infidelity peptides contain specific epitopes of immunoglobulins ; detection of changes in immunoglobulins in patients with cancers opens a novel path toward early stage cancer diagnosis. This increased transcription infidelity in cancer contributes to the heterogeneity of cancer cells. This finding opens novel perspectives and strategies toward understanding carcinogenesis and diagnostic of the diseaseNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

Fat emulsions are more than energy suppliers

The type of triglycerides in exogenous fat emulsions as well as the phospholipids: triglyceride ratio influences the plasma clearance. The plasma clearance cannot be used for indicating the utilization of fat emulsions as energy substrate. Introducing exogenous fat in replacement of part of the calories provided by glucose reduces a series of complications associated with large glucose intake. There are exchanges of triglycerides, esterified cholesterol, phospholipids and apoproteins between exogenous lipids and endogenous lipoproteins, depending on the composition of exogenous lipid emulsions. These interactions can significantly modify the composition of both, exogenous particles and endogenous lipoproteins. In future it will become essential to determine the removal site of 'exogenous remnants'. Future progress will allow a better understanding of the influence of these modifications on the metabolism of endogenous lipoproteins and the utilization of exogenous fat emulsions.SCOPUS: re.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Changes in apolipoprotein and lipids in patients after surgery

Plasma levels of apoproteins A-I, A-II and B and apoprotein/lipid ratios were determined in 43 patients (14 male and 29 female) on the second to the sixth day after gastrointestinal surgery. During this period, all the patients received i.v. 5% dextrose solutions only. Apoprotein levels (A-I, A-II and B), total cholesterol, HDL-cholesterol and phospholipid were significantly decreased after surgery but there was no sex differences. Patients undergoing major surgery showed much lower values than the ones undergoing minor surgery. Both the extent of the trauma and the caloric restriction resulting from sole carbohydrate intravenous feeding may be responsible for these changes. Decreased hepatic synthesis combined to a lack of intestinal supply might result in apo A-I and A-II reduction. Repeated determinations of apoprotein levels are proposed as simple means of follow-up for evaluating the degree of recovery of patients undergoing gastro-intestinal surgery.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Interactions between exogenous fat and plasma/lipoproteins

Fat emulsions are essentially composed of triglycerides and phospholipids. Their elimination from the plasma - which is generally rapid – is influenced by the amount and the composition of both these components. During their short stay in the vascular compartment, exogenous particles undergo major compositional changes. They acquire various apolipoproteins - namely C-II, C-III, E and A-IV - by transfer from HDL. They also acquire esterified cholesterol from HDL and LDL and transfer exogenous triglycerides and phospholipids to these endogenous lipoproteins. These exchanges are affected by the type of triglyceride fatty acids and the amount of phospholipids present in fat emulsions, as well as by the infusion rate. Some 10% of emulsions - with a high phospholipid: Triglyceride ratioSCOPUS: ar.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Plasma lipid and plasma lipoprotein concentrations in low birth weight infants given parenteral nutrition with twenty or ten percent lipid emulsion

Because 10% and 20% intravenously administered lipid emulsions (Intralipid preparations) differ in their phospholipid/triglyceride ratio (0.12 and 0.06, respectively), 28 low birth weight infants requiring parenteral nutrition for at least 1 week were selected at random to receive either emulsion to determine the effects on plasma lipids and lipoproteins. Triglyceride intake was progressively increased to reach 2 gm/kg per day between days 4 and 7. During that period, all plasma lipids in samples taken 6 hours after infusion were higher in the 10% intrallpid group. In comparison with day 0 values, triglyceride concentrations decreased (63±7 to 45±4 mg/dl; p<0.05) in the 20% group. Cholesterol levels increased in both groups, but the rise was more than twofold higher in the 10% group. Phospholipid increase was approximately 25% in the 20% group but more than 125% in patients receiving the 10% emulsion (p<0.005). The changes in plasma cholesterol and phospholipid levels were almost entirely in low-density lipoproteins. After 7 days, eight infants from each group were given the alternate emulsion, which resulted in a reversal of lipid patterns in each patient. We conclude that the higher phospholipid intake in 10% than in 20% intralipid is associated with higher plasma triglyceride concentrations and leads to accumulation of cholesterol and phospholipids in low-density lipoproteins. Emulsions with lower phospholipid content may be preferable for low birth weight infants and perhaps other patient populations with impaired removal of parenteral fat emulsions. © 1989 The C. V. Mosby Company.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Fatty acid control of lipoprotein lipase: A link between energy metabolism and lipid transport

Lipoprotein lipase (LPL) catalyzes the fluxgenerating step in transport of fatty acids from lipoprotein triacylglycerols into tissues for use in metabolic reactions. In vitro studies have shown that fatty acids can bind to the enzyme and impede its other interactions. In this study we have searched for evidence of fatty acid control of LPL in vivo by rapid infusion of a triacylglycerol emulsion to healthy volunteers. During infusion the activity of LPL but not of hepatic lipase increased in plasma, but to different degrees in different individuals. The time course for the increase in LPL activity differed from that for triacylglycerols but followed the plasma levels of free fatty acids. This was true during infusions and when the emulsion was given as a bolus injection. In particular there were several instances when plasma triacylglycerol levels were very high but free fatty acids and LPL activity remained low. Model studies with bovine LPL showed that fatty acids displace the enzyme from heparin-agarose. We suggest that in situations when fatty acids are generated more rapidly by LPL than they are used by the local tissue, they cause dissociation of the enzyme from its binding to endothelial heparan sulfate and are themselves released into circulation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Detection of IgE-reactive proteins in hydrolysed dog foods

BACKGROUND Commercial hydrolysed diets are used for the diagnosis of food allergy in dogs. The cleaved parent proteins are presumed to be too small to elicit an allergic response by reacting with allergen-specific immunoglobin E (IgE). OBJECTIVES To evaluate three commercial hydrolysed dog diets for proteins. ANIMALS Sera were collected from dogs with suspected food allergy. METHODS Two batches of each hydrolysed diet were examined by electrophoresis and visualized by Coomassie blue, silver nitrate staining and IgE immunoblotting. RESULTS From two to five proteins, ranging from 21 to 67 kDa, were detected in all three diets evaluated. Circulating IgE antibodies targeting these proteins were detected by immunoblotting of dog sera. Six different carbohydrate proteins were identified by mass spectrometry; maize/potato granule-bound starch synthase-1, soybean glycinin, soybean β-conglycinin α chain, potato aspartic protease inhibitor, rice glutelin type B1 and soybean sucrose-binding protein. Four of these proteins have been described as allergens in humans. CONCLUSIONS Some commercial hydrolysed diets contain carbohydrate proteins. Some dogs have circulating IgE antibodies targeting these proteins. The clinical significance of these findings is unknown