1,721,226 research outputs found
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
Interleukin-2 (IL-2) activates the CAMP response element binding protein (CREB) in human natural killer (NK) cells.
No full textInhibition of purified CD34+ hematopoietic progenitor cells by humanimmunodeficiency virus 1 or gp120 mediated by endogenous transforming growthfactor beta 1
No full textHuman CD34+ hematopoietic progenitor cells, stringently purified from the
peripheral blood of 20 normal donors, showed an impaired survival and clonogenic
capacity after exposure to either heat-inactivated human immunodeficiency virus
(HIV) 1 (strain IIIB) or cross-linked envelope gp120. Cell cycle analysis,
performed at different times in serum-free liquid culture, showed an accumulation
in G0/G1 in HIV-1- or gp120-treated cells and a progressive increase of cells
with subdiploid DNA content, characteristic of apoptosis. In blocking experiments
with anti-transforming growth factor (TGF) beta 1 neutralizing serum or TGF-beta
1 oligonucleotides, we demonstrated that the HIV-1- or gp120-mediated suppression
of CD34+ cell growth was almost entirely due to an upregulation of endogenous
TGF-beta 1 produced by purified hematopoietic progenitors. Moreover, by using a
sensitive assay on the CCL64 cell line, increased levels of bioactive TGF-beta 1
were recovered in the culture supernatant of HIV-1/gp120-treated CD34+ cells.
Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were also
effective in inducing a significant increase of the plating efficiency of CD34+
cells, purified from the peripheral blood of three HIV-1-seropositive
individuals, suggesting that a similar mechanism may be also operative in vivo.
The relevance of these findings to a better understanding of the pathogenesis of
HIV-1-related cytopenias is discussed
In Vivo Emergence of Ceftazidime/Avibactam, Cefiderocol and Aztreonam/Avibactam Cross-Resistance in a Patient With KPC-Producing Klebsiella pneumoniae Infection After Cefiderocol-Based Treatment
No full textMeaning 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
Colistin: Lights and Shadows of an Older Antibiotic
No full textThe emergence of antimicrobial resistance represents a serious threat to public health and for infections due to multidrug-resistant (MDR) microorganisms, representing one of the most important causes of death worldwide. The renewal of old antimicrobials, such as colistin, has been proposed as a valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to present several adverse toxic effects, its usage in clinical practice has been reconsidered due to its broad spectrum of activity against Gram-negative (GN) bacteria and its important role of "last resort" agent against MDR-GN. Despite the revolutionary perspective of treatment with this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In last years, several forward steps have been made in the understanding of the resistance determinants, clinical usage, and pharmacological dosage of this molecule; however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not yet well defined. In this review, we summarize the mode of action, the emerging resistance determinants, and its optimal administration in the treatment of infections that are difficult to treat due to MDR Gram-negative bacteria
Overexpression of MLH-1 and psoriasin genes in cutaneous angiofibromas from tuberous sclerosis complex patients.
No full textBackground: Tuberous sclerosis complex (TSC) is associated with mutations in two likely tumor-suppressor genes (TSC1 and TSC2) and characterized by the development of tumor-like growths (angiofibromas) in a variety of tissues and organs, particularly brain and skin. Methods: Employing a DNA-microarray assay, able to detect mRNA production from 1176 different basic genes, we analyzed the geneexpression levels in a cutaneous hamartoma sample from a TSC patient. Altered gene expressions detected by microarray technology were further checked by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in the same material and in cutaneous hamartoma samples obtained from five other TSC patients. Results: The results obtained by the microarray technology in one hamartoma specimen, confirmed by the RT-PCR results obtained in the same material and in five other hamartoma specimens, demonstrated that TSC-related angiofibromas exhibit significant mRNA overexpression of two genes, represented by MLH-1 and psoriasin. Conclusions: The overexpression of MLH-1, which codes for a DNA mismatch repair protein, and psoriasin, which codes for a specific chemoattractant factor for CD4þ T cells, implicated in the pathogenesis of inflammatory skin disease, and expressed in excess during abnormal pathways of cell growth, may shed light on the pathogenesis of the proliferative skin lesion
Inhibition of purified CD34+ hematopoietic progenitor cells by HIV-1 is mediated by endogenous TGF-beta 1.
No full textHuman CD34+ hematopoietic progenitor cells, stringently purified from the peripheral blood of 20 normal donors, showed an impaired survival and clonogenic capacity after exposure to either heat-inactivated human immunodeficiency virus (HIV) 1 (strain IIIB) or cross-linked envelope gp120. Cell cycle analysis, performed at different times in serum-free liquid culture, showed an accumulation in G0/G1 in HIV-1- or gp120-treated cells and a progressive increase of cells with subdiploid DNA content, characteristic of apoptosis. In blocking experiments with anti-transforming growth factor (TGF) beta 1 neutralizing serum or TGF-beta 1 oligonucleotides, we demonstrated that the HIV-1- or gp120-mediated suppression of CD34+ cell growth was almost entirely due to an upregulation of endogenous TGF-beta 1 produced by purified hematopoietic progenitors. Moreover, by using a sensitive assay on the CCL64 cell line, increased levels of bioactive TGF-beta 1 were recovered in the culture supernatant of HIV-1/gp120-treated CD34+ cells. Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were also effective in inducing a significant increase of the plating efficiency of CD34+ cells, purified from the peripheral blood of three HIV-1-seropositive individuals, suggesting that a similar mechanism may be also operative in vivo. The relevance of these findings to a better understanding of the pathogenesis of HIV-1-related cytopenias is discussed
- …
