Molecular basis of coagulation factor V deficiency caused by the R1698W inter-domain mutation.

Coagulation factor V (FV) deficiency is characterised by variable bleeding phenotypes and heterogeneous mutations. To add new insights into the FV genotype-phenotype relationship, we characterised the R1698W change in the A3 domain, at the poorly investigated interface with the A2 domain. The FV R1698W mutation was responsible for a markedly reduced expression level (10% of FV-WT) and specific activity in thrombin generation (0.

Individualized Theory of Mind (iToM): When Memory Modulates Empathy.

Functional neuroimaging studies have noted that brain regions supporting theory of mind (ToM) overlap remarkably with those underlying episodic memory, suggesting a link between the two processes. The present study shows that memory for others' past experiences modulates significantly our appraisal of, and reaction to, what is happening to them currently. Participants read the life story of two characters; one had experienced a long series of love-related failures, the other a long series of work-related failures.

Bovine herpesvirus-5 infection in a rabbit experimental model: immunohistochemical study of the cellular response in the CNS.

Since little information is available regarding cellular antigen mapping and the involvement of non-neuronal cells in the pathogenesis of bovine herpesvirus type 5 (BHV-5) infection, it were determined the BHV-5 distribution, the astrocytic reactivity, the involvement of lymphocytes and the presence of matrix metalloproteinase (MMP)-9 in the brain of rabbits experimentally infected with BHV-5. Twelve New Zealand rabbits that were seronegative for BHV-5 were used for virus inoculation, and five rabbits were used as mock-infected controls. The rabbits were kept in separate areas and were inoculated intranasally with 500 μl of virus suspension (EVI 88 Brazilian isolate) into each nostril (virus titer, 10(7.

High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy.

Study Objectives: We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses.

Design: Cross-sectional on consecutive recruitment.

Setting: Hospital sleep center and pediatric unit.

Phytochemical analysis and cytotoxicity towards multidrug-resistant leukemia cells of essential oils derived from Lebanese medicinal plants.

Juniperus excelsa fruit essential oil as well as J. oxycedrus, Cedrus libani, and Pinus pinea wood essential oils have been obtained with yields between 2.2 ± 0.

Lung function outcome at school age in very low birth weight children.

Objective: The aim of this study was to assess pulmonary function and its predictors in very low birth weight (birth weight ≤1,500 g) children (VLBWc) with or without bronchopulmonary dysplasia (BPD), born at gestational age ≤32 weeks at a single tertiary center during 1996-1999, after the introduction of surfactant therapy.

Methods: Of the 120 surviving VLBW children, 48 (40%) VLBWc (22 with prior-BPD) at age 8.5 ± 1.

A mesenteric hernia complicated with a triple necrotic volvulus.

A 6-year-old girl was admitted to the paediatric emergency department with colicky abdominal pain. She had a significant medical history, with four previous admissions due to recurrent abdominal pain in the past year. On examination the abdomen was soft, there was no rebound tenderness and Rovsing's sign was negative.

Management of kidney transplantation in a factor VII-deficient patient: case report.

Transplantation in patients with congenital bleeding disorders is a challenge requiring an integrated approach of various specialists. Renal transplantation, the most frequent type of solid organ transplantation, is rarely performed in individuals with congenital hemorrhagic disorders. We performed a renal transplantation in a 53-year-old man with end-stage renal disease and congenital coagulation factor VII deficiency, a rare bleeding disorder with a peculiar clinical picture requiring replacement therapy in surgical interventions.

Oxidative damage, inflammation, and Toll-like receptor 4 pathway are increased in preeclamptic patients: a case-control study.

Problem: There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE) patients.

Method Of Study: 33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls), inflammatory response (interleukin-6 and myeloperoxidase activity), and activation of the TLR-4-NF-kB pathway.

Immunohistochemical study of the nervous system of the tunicate Thalia democratica (Forsskal, 1775).

Thalia democratica is a cosmopolitan tunicate belonging to the Thaliacea class. To further investigate the anatomy of this species, immunohistochemical labelling was performed using anti-tubulin and anti-serotonin antibodies on specimens collected in the Mediterranean Sea. The anti-tubulin antibody stained the cilia of the endostyle, the pericoronal bands and of the gill bar, enabling a detailed description of these structures.

Mucosa-associated lymphoid tissue lymphoma of the trachea: case report.

Context: Mucosa-associated lymphoid tissue (MALT) lymphomas are most commonly found in the stomach, lungs, orbital soft tissue, salivary glands and thyroid. Involvement of the trachea is extremely rare.

Case Report: This report describes a rare case of MALT lymphoma of the trachea in a 71-year-old woman who presented with a one-year history of coughing, dyspnea, hoarseness and weight loss.

An exon-specific U1 small nuclear RNA (snRNA) strategy to correct splicing defects.

A significant proportion of disease-causing mutations affect precursor-mRNA splicing, inducing skipping of the exon from the mature transcript. Using F9 exon 5, CFTR exon 12 and SMN2 exon 7 models, we characterized natural mutations associated to exon skipping in Haemophilia B, cystic fibrosis and spinal muscular atrophy (SMA), respectively, and the therapeutic splicing rescue by using U1 small nuclear RNA (snRNA). In minigene expression systems, loading of U1 snRNA by complementarity to the normal or mutated donor splice sites (5'ss) corrected the exon skipping caused by mutations at the polypyrimidine tract of the acceptor splice site, at the consensus 5'ss or at exonic regulatory elements.

Promoter methylation in coagulation F7 gene influences plasma FVII concentrations and relates to coronary artery disease.

Background: Plasma factor VII concentrations (FVIIa), a marker of coronary artery disease (CAD) risk, are influenced by genetic markers at the promoter site: the A2 allele, due to a 10bp insertion at position -323, is a determinant of lower FVIIa concentrations and reduced CAD risk, while the -402A allele, due to a G>A substitution, confers increased transcriptional activity in vitro resulting in higher FVIIa. Transcriptional regulation of F7 by epigenetic features is, however, still unknown as is the inter-relationship of genetic and epigenetic modifications at the promoter site.

Objective: To investigate a possible epigenetic regulation of the F7 gene at the promoter region and its link with functional F7 polymorphisms at the same site.

Natural and engineered carboxy-terminal variants: decreased secretion and gain-of-function result in asymptomatic coagulation factor VII deficiency.

We report 2 asymptomatic homozygotes for the nonsense p.R462X mutation affecting the carboxy-terminus of coagulation factor VII (FVII, 466 aminoacids). FVII levels of 3-5% and 2.

Functional genetics.

How genetic variations mediate normal and abnormal biological function is a major issue in biology and medicine. The enormous number of genomic sequences, and their frequent and rare variations identified in humans, require efficient approaches aimed at dissecting functional correlates. In this review we will focus on the importance of the assessment of well-defined intermediate phenotypes, on the set up of transcriptomic approaches in diseased cells and on the modulation of expression by sequence variations modulating mRNA splicing or influencing protein multimerization.

Giant multilocular thymic cyst in an HIV-infected adolescent.

A girl with vertically acquired HIV infection presented with a 6-month history of dyspnea and chest pain. Computed tomography of the thorax showed a heterogenous mass measuring 13 × 9 × 17 cm located in the anterior mediastinum. Complete surgical resection was accomplished with no complications.

RNA-based therapeutic approaches for coagulation factor deficiencies.

Substitutive therapy has significantly ameliorated the quality of life of patients with coagulation factor deficiencies. However, there are some limitations that support research towards alternative therapeutic approaches. Here we focus on the rescue of coagulation factor biosynthesis by targeting the RNA processing and translation, which would permit restoration of the altered gene expression while maintaining the gene regulation in the physiological tissues.