Expression of a splice variant of the platelet-activating factor receptor transcript 2 in various human cancer cell lines.

Platelet-activating factor receptor (PAF-R) transcripts were analysed by reverse transcriptase-polymerase chain reaction in five human cancer cell lines derived from the breast (BT20, SKBR3 and T47D cells), the pancreas (Miapaca cells) and the bladder (5,637 cells) in order to confirm the existence of a splice variant of the PAF-R transcript 2. After cloning and sequencing, we confirmed its existence in all cell lines. It consisted of the PAF-R transcript 2 lengthening with 82 nucleotides from the 3' end of exon 1 of the PAF-R gene. The role of this elongated form of the tissue-type PAF-R transcript in cell physiology remains to be elucidated

Lipid Mediators and Human Leukemic Blasts

Some of the most potent inflammatory mediators share a lipid origin. They regulate a wide spectrum of cellular processes including cell proliferation and apoptosis. However, the precise roles and ways (if any) in which these compounds impact the growth and apoptosis of leukemic blasts remain incompletely resolved. In spite of this, significant advances have been recently made. Here we briefly review the current knowledge about the production of lipid mediators (prostaglandins, leukotrienes, platelet-activating factor) by leukemic blasts, the enzymatic activities (phospholipase A2, cyclooxygenases, lipoxygenases) involved in their productions and their effects (through specific membrane bound receptors) on the growth, and apoptosis of leukemic blasts

Elevated plasma phospholipase A2 and platelet-activating factor acetylhydrolase activity in colorectal cancer.

This clinical study reports that blood levels of the pro-inflammatory mediator platelet-activating factor (PAF) did not change in colorectal cancer patients. In contrast, plasma levels of two enzymatic activities, one implicated in PAF production (i.e. phospholipase A2) and one in PAF degradation (i.e. PAF acetylhydrolase activity) were significantly elevated

Genes encoding multiple forms of phospholipase A(2) are expressed in immature forms of human leukemic blasts.

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Alleles of the α1 immunoglobulin gene 3′ enhancer control evolution of IgA nephropathy toward renal failure

Alleles of the α1 immunoglobulin gene 3′ enhancer control evolution of IgA nephropathy toward renal failure.BackgroundIgA nephropathy is the most common glomerular disease. Mechanisms leading to its occurrence and controlling the evolution of the disease remain largely unknown. Various genetic factors have been found, mostly implicating immunologically relevant genes (IgH, TCR, human lymphocyte antigen, and complement loci). A regulatory region recently identified downstream, the α1 gene of the IgH locus, was a likely candidate for the control of IgA1 production in patients. Alleles of this region, differing by size, sequence, and orientation of the α1 hs1,2 transcriptional enhancer, were first identified through Southern blot hybridization.MethodsWe established a polymerase chain reaction (PCR) method suitable for routine testing that amplifies minisatellites within the α1 hs1,2 enhancer, with variable numbers of tandem repeats (VNTR) defining the two alleles. This assay allowed the typing of 104 patients with IgAN and 83 healthy volunteers. Results from typing of α1 hs1,2 alleles were compared with long-term clinical outcome in patients. Enhancer alleles were compared in a luciferase reporter gene assay.ResultsThe α1 hs1,2 alleles do not constitute a predictive factor for IgA nephropathy, since similar allelic frequencies were observed in healthy individuals and in unrelated European patients. In contrast, among patients, homozygosity for the weakest enhancer allele (AA genotype) was significantly correlated with a milder form of the disease, whereas the allele B was associated with severe evolution. The minisatellite region within the α1 hs1,2 enhancer carried potential transcription factor-binding sites, and its duplication increased the transcriptional strength of the α1 hs1,2 allele B over that of allele A.ConclusionAltogether, these alleles may constitute a risk factor for the prognosis of IgA nephropathy

No evidence for a putative involvement of platelet-activating factor in systemic lupus erythematosus without active nephritis.

BACKGROUND: Platelet-activating factor (PAF) seems to be implicated in systemic lupus erythematosus (SLE) patients with associated renal diseases. AIMS: In this study, we ensured the role of PAF in SLE patients without renal complications. METHODS: Blood PAF and acetylhydrolase activity, plasma soluble phospholipase A(2), and the presence of antibodies against PAF were investigated in 17 SLE patients without active nephritis and in 17 healthy controls. RESULTS: Blood PAF levels were not different (p=0.45) between SLE patients (6.7+/-2.8 pg/ml) and healthy subjects (9.6+/-3.1 pg/ml). Plasma acetylhydrolase activity (the PAF-degrading enzyme) was significantly (p=0.03) elevated in SLE patients (57.8+/-6.4 nmol/min/ml) as compared with controls (37.9+/-2.6 nmol/min/ml). Plasma soluble phospholipase A(2) (the key enzyme for PAF formation) was not different (p=0.6) between SLE patients (59.1+/-5.1 U/ml) and controls (54.7+/-2.4 U/ml). Antibodies against PAF were detected only in 3/17 SLE patients. Flow cytometry analysis did not highlight PAF receptors on circulating leukocytes of SLE patients. CONCLUSION: This clinical study highlights no evidence for a putative important role of PAF in SLE patients without active nephritis

Hyperbilirubinemia and Neurodevelopmental Outcome of Very Low Birthweight Infants: Results from the LIFT Cohort

Bilirubin-related neurotoxicity is an important clinical issue in very low birthweight (VLBW) infants, and the existing literature is inconsistent.To analyze the relationship between maximal serum unconjugated bilirubin levels (SBL) and neurodevelopmental outcome at 2-year corrected age in VLBW infants.Phototherapy was initiated in all infants born before 33 weeks of gestation, according to Maisels' recommendations. Neurodevelopmental assessment at 2-year corrected age was performed in all infants that survived. SBLs collected during the first week of life were used to define three tertiles of max-SBL. The first tertile corresponded to infants with the lowest max-SBL. percentile curves of SBLs in infants with an optimal outcome). When Maisels' recommendations were applied, max SBLs were higher in 8% of infants weighing 1001–1500 g and in 15% of infants weighing less than 1001 g. Our data seems to validate Maisels' recommendations in the overall population of infants born before 33 weeks of gestation, but not in infants weighing less than 1001 g

Analysis of Several PLA2 mRNA in Human Meningiomas

In view of the important oncogenic action of phospholipase A2(PLA2) we investigated PLA2 transcripts in human meningiomas. Real-time PCR was used to investigate PLA2 transcripts in 26 human meningioma tumors. Results indicated that three Ca2+-dependent high molecular weight PLA2 (PLA2-IVA, PLA2-IVB, PLA2-IVC), one Ca2+-independent high molecular weight PLA2 (PLA2-VI) and five low molecular weight secreted forms of PLA2 (PLA2-IB, PLA2-IIA, PLA2-III, PLA2-V, and PLA2-XII) are expressed with PLA2-IVA, PLA2-IVB, PLA2-VI, and PLA2-XIIA as the major expressed forms. PLA2-IIE, PLA2-IIF, PLA2-IVD, and PLA2-XIIB are not detected. Plasma (PLA2-VIIA) and intracellular (PLA2-VIIB) platelet-activating factor acetylhydrolase transcripts are expressed in human meningiomas. However no difference was found for PLA2 transcript amounts in relation to the tumor grade, the subtype of meningiomas, the presence of inflammatory infiltrated cells, of an associated edema, mitosis, brain invasion, vascularisation or necrosis. In conclusion numerous genes encoding multiples forms of PLA2 are expressed in meningiomas where they might act on the phospholipid remodeling and on the local eicosanoid and/or cytokine networks

Alterations in plasma soluble vascular endothelial growth factor receptor-1 (sFlt-1) concentrations during coronary artery bypass graft surgery: relationships with post-operative complications

<p>Abstract</p> <p>Background</p> <p>Plasma concentrations of sFlt-1, the soluble form of the vascular endothelial growth factor receptor (VEGF), markedly increase during coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). We investigated if plasma sFlt-1 values might be related to the occurrence of surgical complications after CABG.</p> <p>Methods</p> <p>Plasma samples were collected from the radial artery catheter before vascular cannulation and after opening the chest, at the end of ECC just before clamp release, after cross release, after weaning from ECC, at the 6^thand 24^thpost-operative hour. Thirty one patients were investigated. The presence of cardiovascular, haematological and respiratory dysfunctions was prospectively assessed. Plasma sFlt-1 levels were measured with commercially ELISA kits.</p> <p>Results</p> <p>Among the 31 investigated patients, 15 had uneventful surgery. Patients with and without complications had similar pre-operative plasma sFlt-1 levels. Lowered plasma sFlt-1 levels were observed at the end of ECC in patients with haematological (p = 0.001, ANOVA) or cardiovascular (p = 0.006) impairments, but not with respiratory ones (p = 0.053), as compared to patients with uneventful surgery.</p> <p>Conclusion</p> <p>These results identify an association between specific post-CABG complication and the lower release of sFlt-1 during ECC. sFlt-1-induced VEGF neutralisation might, thus, be beneficial to reduce the development of post-operative adverse effects after CABG.</p

Compression irréversible par ondelettes en radiologie thoracique numérique : Evaluation qualitative sur des structures anatomiques et pathologiques

La compression d'images représente une alternative de faible coût à l'augmentation systématique de la capacité de stockage des systèmes d'archivage et des lignes de transmission (PACS). Afin d'étudier les effets de la compression irréversible par ondelettes (base de la norme JPEG2000) sur des radiographies thoraciques d'emblée numériques (Thoravision®), nous avons défini un protocole complet d'évaluation. Les taux de compression de 20:1, 40:1, 60:1 ont été évalués en double aveugle par 3 radiologues dans des conditions standardisées sur des structures anatomiques (suivant 11 critères portant sur les détails, les contours et les artéfacts sur une population de 30 sujets sains) et pathologiques (pneumothorax et syndromes interstitiels). Des courbes ROC ont été réalisées à partir de deux populations de 20 patients. Notre étude détermine un taux de compression acceptable à 20:1 pour les radiographies normales et 60:1 pour les images pathologiques. L'interprétation rigoureuse d'une radiographie thoracique nécessitant la conservation des structures anatomiques, le taux de 20:1 apparaît être la limite acceptable en pratique clinique. Notre protocole d'évaluation suggère par ailleurs qu'une évaluation qualitative d'une compression par ondelettes de radiographie thoracique peut être réalisée uniquement sur des critères anatomiques portant sur la vascularisation fine du poumon où la dégradation est prédominante