Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas.
View Article and Find Full Text PDFObjectives: In this study, we investigated the causes of measles-like illnesses (MLI) in the Uganda national surveillance program in order to inform diagnostic assay selection and vaccination strategies.
Methods: We used metagenomic next-generation sequencing (M-NGS) on the Illumina platform to identify viruses associated with MLI (defined as fever and rash in the presence of either cough, coryza or conjunctivitis) in patient samples that had tested IgM negative for measles between 2010 and 2019.
Results: Viral genomes were identified in 87/271 (32%) of samples, of which 44/271 (16%) contained 12 known viral pathogens.
Objectives: Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool.
Methods: Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays.
Replicon systems are important tools for investigating viral RNA synthesis. We have developed an ambisense minigenome system for Rift Valley fever virus (RVFV) with the aim to analyse the effects of L gene mutations on viral transcription versus replication. The overall activity of the replication complex was assessed by expression of a luciferase reporter gene.
View Article and Find Full Text PDFThis study examined the effectiveness of a novel cancer bereavement group. Twenty-seven participants attended a sixsession cancer bereavement therapeutic group. Data were collected at baseline, intervention completion, and three-month follow-up.
View Article and Find Full Text PDFGallbladder torsion is a rare entity, where the gallbladder twisted around its mesentery. Unfortunately, the diagnosis is rarely done preoperatively. This paper aims, through a case report, to describe the risk factors and the radiological criteria used to diagnose gallbladder torsion, in order to avoid a rapidly unfavourable evolution and the need to proceed to emergency cholecystectomy.
View Article and Find Full Text PDFLassa virus (LASV) causes a deadly haemorrhagic fever in humans, killing several thousand people in West Africa annually. For 40 years, the Natal multimammate rat, Mastomys natalensis, has been assumed to be the sole host of LASV. We found evidence that LASV is also hosted by other rodent species: the African wood mouse Hylomyscus pamfi in Nigeria, and the Guinea multimammate mouse Mastomys erythroleucus in both Nigeria and Guinea.
View Article and Find Full Text PDFThe N terminus of arenavirus L protein contains an endonuclease presumably involved in "cap snatching." Here, we employed the Lassa virus replicon system to map other L protein sites that might be involved in this mechanism. Residues Phe-1979, Arg-2018, Phe-2071, Asp-2106, Trp-2173, Tyr-2179, Arg-2200, and Arg-2204 were important for viral mRNA synthesis but dispensable for genome replication.
View Article and Find Full Text PDFThe human complement regulatory serum protein factor H (FH) is a promising future biopharmaceutical. Defects in the gene encoding FH are associated with human diseases like severe kidney and retinal disorders in the form of atypical haemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis II (MPGN II) or age-related macular degeneration (AMD). There is a current need to apply intact full-length FH for the therapy of patients with congenital or acquired defects of this protein.
View Article and Find Full Text PDFFocal adhesion kinase (FAK), a 125 kDa protein, is located at the focal adhesion sites that stabilize endothelial cells on the matrix. Ischemic stimuli cause FAK cleavage and FAK depletion from focal adhesion sites. To test this hypothesis under ischemic conditions, we established an isolated rat lung that we ventilated at 40 inflations/min at inspiratory and expiratory pressures of 10 and 3 cm H2O, respectively.
View Article and Find Full Text PDFFocal adhesion kinase (FAK) is a 125 kDa protein tyrosine kinase (PTK) associated with focal adhesion in many cells, which plays a major role in the integrity of cytoskeletal structure. Reactive oxygen species produced during ischemia and reperfusion injury has been found to be an important mediator of signal transduction process. We found that low dose H2O2 induced increased FAK production in pulmonary microvascular endothelial cells, which could be blocked by cycloheximide (CHX), a protein synthesis inhibitor.
View Article and Find Full Text PDFAcute lung injury produces pulmonary hypertension, altered vascular reactivity, and endothelial injury. To determine whether acute lung injury impairs the endothelium-dependent regulation of pulmonary vascular tone, 16 lambs were studied during U46619-induced pulmonary hypertension without acute lung injury, or air embolization-induced pulmonary hypertension with acute lung injury. The hemodynamic responses to endothelium-dependent (acetylcholine, ATP, ET-1, and 4 Ala ET-1 [an ETb receptor agonist]) and endothelium-independent (nitroprusside and isoproterenol) vasodilators were compared.
View Article and Find Full Text PDFThe ability of a macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]40) to allow distinction of pulmonary capillary leak from hydrostatic pulmonary edema was investigated. Capillary leak edema was induced in 12 rats by means of venous injection of oleic acid; hydrostatic pulmonary edema was induced in 10 rats by means of continuous infusion of 0.9% sodium chloride.
View Article and Find Full Text PDFThe molecular cloning and nucleotide sequence of a cDNA clone (pR SOD) for rat CuZn superoxide dismutase (CuZnSOD) is reported. Nucleotide sequence homology with human superoxide dismutase is 86% for the coding region and 71% for the 3' untranslated region. The deduced amino acid sequence is given and the homologies with the sequences reported for other species are presented.
View Article and Find Full Text PDFBull Acad Natl Med
December 1985
The enzymatic activity of phosphoribosylglycinamide synthetase (GARS) has been studied in several cases of partial monosomies and full and partial trisomies 21. An excess of GARS activity was found in regular trisomy 21 with a trisomy 21/normal ratio equal to 1.55.
View Article and Find Full Text PDFBiochim Biophys Acta
August 1983
A method for the assessment of both selenium-dependent and non-selenium-dependent glutathione peroxidases on crude tissue extracts in human is described. The enzyme activity is measured by the coupled assay system in which oxidation of reduced glutathione (GSH) is coupled to NADPH oxidation catalyzed by glutathione reductase. Total glutathione peroxidase activity is measured with cumene hydroperoxide as substrate.
View Article and Find Full Text PDFCystic fibrosis (CF) has recently been linked to the group of human diseases in which cultured fibroblasts express premature aging. As the deleterious effect of oxygen derivatives in the cell is one of the numerous pathways associated with cell aging, the activity of the enzymatic defense system, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione reductase (GR), was examined in the erythrocytes of 12 CF children and was compared to age-matched normal controls. No significant differences were found in CF children when compared to the controls.
View Article and Find Full Text PDFHuman red blood cells treated with the CuZn superoxide dismutase inhibitor diethyldithiocarbamate (DDC) undergo metabolic modifications in addition to the superoxide dismutase inhibition: oxidation of the reduced glutathione (GSH) to oxidized glutathione (GSSG), methemoglobin formation, and increased hexose monophosphate shunt activity were observed. The magnitudes of these changes are dependent on the DDC concentration. Under nitrogen, only superoxide dismutase inhibition occurs.
View Article and Find Full Text PDFRecently Meisler et al. (1980) reported the results of mouse/human somatic cell hybrid studies which indicated that the locus for human uroporphyrinogen I synthase (UPS) (EC 4.3.
View Article and Find Full Text PDFAn assay for human erythrocyte glutathione-S-transferase is described. The procedure is both sensitive and reproducible; sampling and storage conditions are also investigated. Reference values are given for normal neonates, children and adults.
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