Stable triple helices formed by oligonucleotide N3'-->P5' phosphoramidates inhibit transcription elongation.

Oligonucleotide analogs with N3'-->P5' phosphoramidate linkages bind to the major groove of double-helical DNA at specific oligopurine.oligopyrimidine sequences. These triple-helical complexes are much more stable than those formed by oligonucleotides with natural phosphodiester linkages. Oligonucleotide phosphoramidates containing thymine and cytosine or thymine, cytosine, and guanine bind strongly to the polypurine tract of human immunodeficiency virus proviral DNA under physiological conditions. Site-specific cleavage by the Dra I restriction enzyme at the 5' end of the polypurine sequence was inhibited by triplex formation. A eukaryotic transcription assay was used to investigate the effect of oligophosphoramidate binding to the polypurine tract sequence on transcription of the type 1 human immunodeficiency virus nef gene under the control of a cytomegalovirus promoter. An efficient arrest of RNA polymerase II was observed at the specific triplex site at submicromolar concentrations.

Behavioral Differences in the Upper and Lower Visual Hemifields in Shape and Motion Perception.

Perceptual accuracy is known to be influenced by stimuli location within the visual field. In particular, it seems to be enhanced in the lower visual hemifield (VH) for motion and space processing, and in the upper VH for object and face processing. The origins of such asymmetries are attributed to attentional biases across the visual field, and in the functional organization of the visual system. In this article, we tested content-dependent perceptual asymmetries in different regions of the visual field. Twenty-five healthy volunteers participated in this study. They performed three visual tests involving perception of shapes, orientation and motion, in the four quadrants of the visual field. The results of the visual tests showed that perceptual accuracy was better in the lower than in the upper visual field for motion perception, and better in the upper than in the lower visual field for shape perception. Orientation perception did not show any vertical bias. No difference was found when comparing right and left VHs. The functional organization of the visual system seems to indicate that the dorsal and the ventral visual streams, responsible for motion and shape perception, respectively, show a bias for the lower and upper VHs, respectively. Such a bias depends on the content of the visual information.

In search of the American tradition.

Mode of access: Internet.

Development of a non-intrusive heat transfer coefficient gauge and its application to high pressure die casting Effect of the process parameters

A heat transfer coefficient gauge has been built, obeying particular rules in order to ensure the relevance and accuracy of the collected information. The gauge body is made out of the same materials as the die casting die (H13). It is equipped with six thermocouples located at different depths in the body and with a sapphire light pipe. The light pipe is linked to an optic fibre, which is connected to a monochromatic pyrometer. Thermocouples and pyrometer measurements are recorded with a data logger. A high pressure die casting die was instrumented with one such gauge. A set of 150 castings was done and the data recorded. During the casting, some process parameters have been modified such as piston velocity, intensification pressure, delay before switch to the intensification stage, temperature of the alloy, etc.... The data was treated with an inverse method in order to transform temperature measurements into heat flux density and heat transfer coefficient plots. The piston velocity and the initial temperature of the die seem to be the process parameters that have the greatest influence on the heat transfer. (c) 2005 Elsevier B.V. All rights reserved.

Studies of the metabolism and the toxicity of N-Methylformamide and related amides

The hepatotoxicity of the industrial solvent and investigational anti-tumour agent N-methylformamide (NMF, HOCNHCH3) and several structural analogues was assessed in mice. NMF and its ethyl analogue (NEF) were equipotent hepatotoxins causing extensive centrilobular necrosis and damage to the gall bladder. Pretreatment of mice with SKF525A did not influence the toxicity of these N-alkylformamides. Replacement of the formyl hydrogen of NMF with deuterium or methyl significantly reduced its hepatotoxicity. An in vitro model for the study of the toxicity and metabolism of N-alkylformamides was developed using isolated mouse hepatocytes. The cytotoxicity of NMF in vitro was concentration-dependent with maximal toxicity being achieved at concentrations of 5mM or above. The cytotoxic potential of related amides correlated well with their in vivo hepatotoxic potential. Pretreatment of mice with buthionine sulphoximine (BSO), which depleted hepatocytic levels of glutathione to 15% of control values, exacerbated the cytotoxicity of NMF towards the hepatocytes. NMF (1mM or above), incubated with isolated mouse hepatocytes, depleted intracellular glutathione levels to 26% of control values within 4h. Depletion of glutathione was quantitatively matched by the formation of a carbamoylating metabolite. Metabolism was dependent on the concentration of NMF and was drastically reduced in incubations of hepatocytes isolated from mice pretreated with BSO. The carbamoylating metabolite, S-(N-methylcarbamoyl)-glutathione (SMG), was identified in vitro using FAB-MS. The generation of SMG was subject to a large primary H/D kinetic isotope effect when the formyl hydrogen was replaced with deuterium. Likewise, glutathione depletion and metabolite formation were reduced or abolished by the deuteration or methylation of the formyl moiety of NMF. NEF, like NMF, depleted hepatocytic glutathione levels and was metabolised to a carbamoylating metabolite. Radioactivity derived from 14C-NMF and 14C-NEF, labelled in the alkyl moieties, was found to be irreversibly associated with microsomal protein on incubation in vitro. Binding was dependent on the presence of NADPH and was mostly abolished in the presence of reduced glutathione. SKF525A failed to influence the binding.

Hepatite C crônica em serviço de referência no nordeste do Brasil: um estudo retrospectivo de dezoito anos de acompanhamento

Chronic Hepatitis C is the leading cause of chronic liver disease in advanced final stage of hepatocellular carcinoma (HCC) and of death related to liver disease. Evolves progressively in time 20-30 years. Evolutionary rates vary depending on factors virus, host and behavior. This study evaluated the impact of hepatitis C on the lives of patients treated at a referral service in Hepatology of the University Hospital Onofre Lopes - Liver Study Group - from May 1995 to December 2013. A retrospective evaluation was performed on 10,304 records, in order to build a cohort of patients with hepatitis C, in which all individuals had their diagnosis confirmed by gold standard molecular biological test. Data were obtained directly from patient charts and recorded in an Excel spreadsheet, previously built, following an elaborate encoding with the study variables, which constitute individual data and prognostic factors defined in the literature in the progression of chronic hepatitis C. The Research Ethics Committee approved the project. The results were statistically analyzed with the Chi-square test and Fisher's exact used to verify the association between variable for the multivariate analysis, we used the Binomial Logistic regression method. For both tests, it was assumed significance p < 0.05 and 95%. The results showed that the prevalence of chronic hepatitis C in NEF was 4.96 %. The prevalence of cirrhosis due to hepatitis C was 13.7%. The prevalence of diabetes in patients with Hepatitis C was 8.78 % and diabetes in cirrhotic patients with hepatitis C 38.0 %. The prevalence of HCC was 5.45%. The clinical follow-up discontinuation rates were 67.5 %. The mortality in confirmed cases without cirrhosis was 4.10% and 32.1% in cirrhotic patients. The factors associated with the development of cirrhosis were genotype 1 (p = 0.0015) and bilirubin > 1.3 mg % (p = 0.0017). Factors associated with mortality were age over 35 years, abandon treatment, diabetes, insulin use, AST> 60 IU, ALT> 60 IU, high total bilirubin, extended TAP, INR high, low albumin, treatment withdrawal, cirrhosis and hepatocarcinoma. The occurrence of diabetes mellitus increased mortality of patients with hepatitis C in 6 times. Variables associated with the diagnosis of cirrhosis by us were blood donor (odds ratio 0.24, p = 0.044) and professional athlete (odds ratio 0.18, p = 0.35). It is reasonable to consider a revaluation in screening models for CHC currently proposed. The condition of cirrhosis and diabetes modifies the clinical course of patients with chronical hepatitis C, making it a disease more mortality. However, being a blood donor or professional athlete is a protective factor that reduces the risk of cirrhosis, independent of alcohol consumption. Public policies to better efficient access, hosting and resolution are needed for this population.

Rôle de la protéine virale Vpu dans le cycle de multiplication du virus de l'immunodéficience humaine de type 1 (VIH-1)

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Characterization of plasmacytoid dendritic cells in the CD4C/HIV transgenic mouse model

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Rôle de la protéine virale Vpu dans le cycle de multiplication du virus de l'immunodéficience humaine de type 1 (VIH-1)

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Characterization of plasmacytoid dendritic cells in the CD4C/HIV transgenic mouse model

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Improvement of Mineral and Bone Metabolism Markers Is Associated with Better Survival in Haemodialysis Patients: the COSMOS Study

BACKGROUND: Abnormalities in serum phosphorus, calcium and parathyroid hormone (PTH) have been associated with poor survival in haemodialysis patients. This COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis assesses the association of high and low serum phosphorus, calcium and PTH with a relative risk of mortality. Furthermore, the impact of changes in these parameters on the relative risk of mortality throughout the 3-year follow-up has been investigated. METHODS:COSMOS is a 3-year, multicentre, open-cohort, prospective study carried out in 6797 adult chronic haemodialysis patients randomly selected from 20 European countries. RESULTS:Using Cox proportional hazard regression models and penalized splines analysis, it was found that both high and low serum phosphorus, calcium and PTH were associated with a higher risk of mortality. The serum values associated with the minimum relative risk of mortality were 4.4 mg/dL for serum phosphorus, 8.8 mg/dL for serum calcium and 398 pg/mL for serum PTH. The lowest mortality risk ranges obtained using as base the previous values were 3.6-5.2 mg/dL for serum phosphorus, 7.9-9.5 mg/dL for serum calcium and 168-674 pg/mL for serum PTH. Decreases in serum phosphorus and calcium and increases in serum PTH in patients with baseline values of >5.2 mg/dL (phosphorus), >9.5 mg/dL (calcium) and <168 pg/mL (PTH), respectively, were associated with improved survival. CONCLUSIONS:COSMOS provides evidence of the association of serum phosphorus, calcium and PTH and mortality, and suggests survival benefits of controlling chronic kidney disease-mineral and bone disorder biochemical parameters in CKD5D patients.

Dabigatran-Related Nephropathy in a Patient with Undiagnosed IgA Nephropathy

Dabigatran is a direct thrombin inhibitor used as an alternative to warfarin for long term anticoagulation. Warfarin-related nephropathy is an increasingly recognized entity, but recent evidence suggests that dabigatran can cause a WRN-like syndrome. We describe a case of a biopsy-proven anticoagulant nephropathy related to dabigatran in a patient with IgA nephropathy and propose that, despite the base glomerular disease, acute kidney injury was due to tubular obstruction by red blood cells and heme-associated tubular injury, and through a mechanism involving inhibition of anticoagulation cascade and barrier abnormalities caused by molecular mechanisms.