130,457 research outputs found
Meaning of DNA detection during the follow-up of HIV-1 infected patients: a brief review.
No full textA growing body of evidence indicates that proviral DNA load quantitation is an important parameter in establishing the dynamics of HIV infection. Proviral DNA load can be determined during the follow-up of infected individuals to evaluate reservoir status in addition to viral replication. Hence, the study of viral reservoirs, represented by HIV-1 latently infected cells, including resting memory CD4+ T cells, monocytes and macrophages, by which HIV-1 can be reactivated, opens new perspectives in the assessment and the comprehension of HIV-1 infection. However, the identification of viral reservoirs, that can store both wild and drug resistance viruses, is one of the most important steps in developing treatment strategies because it is now clear that viral reservoirs not only prevent sterilizing immunity but also represent a major obstacle to curing the infection with the potent antiretroviral drugs currently in use. Even if only careful evaluation of virological and immunological markers is necessary to fully characterize the course of HIV-1 infection and to provide a more complete laboratory-based assessment of disease progression, the availability of a new standardized assay such as DNA proviral load will be important to assess the true extent of virological suppression in treated patients and to verify the efficacy of new immune-based therapies aimed at purging HIV-1 DNA reservoirs. Several studies demonstrate, in fact, that HIV-1 cellular DNA load may be an indicator of spread of infection whereas the plasma RNA load is indicates active infection. This article will review the importance of monitoring HIV-1 proviral load DNA during the follow-up of HIV-1 infected subjects, suggesting that additional information complementing HIV RNA load could provide crucial information to monitor viral replication and the effectiveness of HAART therapy
Discordant resistance interpretations in multi-treated HIV-1 patients.
No full textThe routine determination of drug resistance has become an important part of the clinical management of HIV-1 infected patients. Plasma samples from 130 individuals treated for at least 1 year with multiple NRTIs and NNRTIs were tested for the presence of mutations correlated to drug resistance. Since interpretation criteria represent a crucial point for virologists and clinicians, often complicated by the presence of novel and/or complex mutations patterns, we analyzed results interpreted by TruGene HIV-1 (Visible Genetics, Toronto, Ontario, Canada) and VirtualPhenotype (Virco, Mechelen, Belgium). A high degree of concordance was found for NNRTIs whereas NRTIs interpretation was highly discrepant. Since different approaches to monitoring resistance reflect different interpretation of results, the prediction of drugs resistance from a given HIV sequence might be contradictory and requires accurate standardization and unique interpretative rules
Antibody to HIV-1 Tat protein, a key molecule in HIV-1 pathogenesis. A brief review
No full textIn the last few years, literature reports have unequivocally established that the 86-101 aminoacid Tat protein, essential for an efficient viral replication, can be actively secreted by infected cells. The contribution of extracellular Tat to the progression of viral infection is underlined by the ability of neutralizing anti Tat antibody to reduce the viral load in vitro and possibly also in vivo. Considering that at least some of the effect of Tat protein seem to be the consequence of an autocrine loop and that anti Tat antibody is an efficient inhibitor of viral replication, it is reasonable to suppose that extracellular Tat play a functional role in HIV-1 infection and that HIV antibody may interfere with a possible Tat driven pathogenesis. This review explores the meaning of anti Tat antibody in vitro and in vivo and its importance to shed more light on viral pathogenesis and the recent development of Tat containing vaccine
HIV-1 tat protein and cell proliferation and survival: a brief review.
No full textMany studies have demonstrated that HIV-1 Tat plays a pivotal role both in the HIV-1 replication cycle and in the pathogenesis of HIV-1 infection. Indeed, Tat affects the HIV-1 replication cycle regulation increasing the proviral transcription rate several hundred-fold and acting on the elongation of viral transcripts. Moreover, Tat displays several important biological activities committed to uninfected and infected cells by a paracrine/autocrine mechanism due to secretion of Tat from infected cells. In particular, Tat modulates the expression of several cellular genes and triggers the activation of some signal transduction pathways and transcription factors suggesting a complex role in the scenario of HIV-1 infection. This review focuses on some aspects of Tat biological activity with particular regard to effects of Tat on cell proliferation and survival regulation
Quantitative DNA proviral detection in HIV-1 patients treated with antiretroviral therapy
No full textThe amount of proviral DNA in peripheral blood mononuclear cells (PBMCs) from 93 HIV-1 seropositive patients on long-lasting antiretroviral therapy was measured by the SYBR green real-time PCR technique. Variable levels of proviral DNA, ranging from 14 to 1847 copies of HIV-1 DNA per 106 PBMC were found, without a significant correlation between proviral load and plasma HIV-1 RNA levels or CD4+ lymphocyte counts. To investigate the possible role of HIV-1 DNA levels as prognostic markers in clinical practice, the amount of proviral DNA and peripheral blood CD4+ lymphocyte counts were further evaluated after 5 months of continued therapy in 32 patients who maintained a persistently undetectable viremia throughout the observation period. Interestingly, a clear-cut decrease (≥0.5 log) in proviralDNAlevelswas significantly associated with a definite increase in CD4+ lymphocyte counts. Even though plasma HIV-1 RNA levels remain the basic parameter to monitor both the intensity of viral replication and the efficacy of therapeutic interventions, the results obtained in our study seem to indicate that measuring proviral DNA levels could represent an adjunct prognostic marker, especially useful in patients whose HIV-1 RNA levels drop below detectable limits
Geotechnical investigation of submarine sediments for the environmental characterisation of a contaminated site.
No full textThe stepwise dissociation of the Zn(II)-bound Atox1 homodimer and its energetic asymmetry
No full textThe copper chaperone Atox1, which is featured by a peculiar CxxC metal-binding motif, is a protein involved in copper trafficking to the Golgi organelle, allowing the delivery of copper ions to specific target proteins in the secretory pathway. Various experimental studies suggest that this cysteine-containing protein may also be implicated in Zn(II) ion binding, functioning as a regulatory factor. However, despite the relevance of this interaction, the mechanism of zinc ion dissociation from the Atox1 homodimer has not yet been elucidated. We herein devised a simulation workflow based on the combination of parallel bias metadynamics and free energy perturbation theory, to predict the dissociation of the zinc ion from the Atox1 homodimer. The freeenergy simulations successfully predicted the dissociation free energy differences of the process, disclosing a mechanism based on a stepwise dissociation pathway of the zinc ion from the Atox1 homodimer
Discordant resistance interpretations in multi-treated HIV-1 patients
No full textThe routine determination of drug resistance has become an important part of the clinical management of HIV-1 infected patients. Plasma samples from 130 individuals treated for at least 1 year with multiple NRTIs and NNRTIs were tested for the presence of mutations correlated to drug resistance. Since interpretation criteria represent a crucial point for virologists and clinicians, often complicated by the presence of novel and/or complex mutations patterns, we analyzed results interpreted by TruGene HIV-1 (Visible Genetics, Toronto, Ontario, Canada) and VirtualPhenotype (Virco, Mechelen, Belgium). A high degree of concordance was found for NNRTIs whereas NRTIs interpretation was highly discrepant. Since different approaches to monitoring resistance reflect different interpretation of results, the prediction of drugs resistance from a given HIV sequence might be contradictory and requires accurate standardization and unique interpretative rules
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Quantitative DNA proviral detection in HIV-1 patients treated with antiretroviral therapy.
No full textThe amount of proviral DNA in peripheral blood mononuclear cells (PBMCs) from 93 HIV-1 seropositive patients on long-lasting antiretroviral therapy was measured by the SYBR green real-time PCR technique. Variable levels of proviral DNA, ranging from 14 to 1847 copies of HIV-1 DNA per 10(6) PBMC were found, without a significant correlation between proviral load and plasma HIV-1 RNA levels or CD4(+) lymphocyte counts. To investigate the possible role of HIV-1 DNA levels as prognostic markers in clinical practice, the amount of proviral DNA and peripheral blood CD4(+) lymphocyte counts were further evaluated after 5 months of continued therapy in 32 patients who maintained a persistently undetectable viremia throughout the observation period. Interestingly, a clear-cut decrease (> or =0.5 log) in proviral DNA levels was significantly associated with a definite increase in CD4(+) lymphocyte counts. Even though plasma HIV-1 RNA levels remain the basic parameter to monitor both the intensity of viral replication and the efficacy of therapeutic interventions, the results obtained in our study seem to indicate that measuring proviral DNA levels could represent an adjunct prognostic marker, especially useful in patients whose HIV-1 RNA levels drop below detectable limits
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