116 research outputs found
Reduction of Immune Activation and Partial Recovery of Staphylococcal Enterotoxin B-Induced Cytokine Production After Switching to an Integrase Strand Transfer Inhibitor-Containing Regimen: Results from an Observational Cohort Study
No full textDespite integrase strand transfer inhibitor (INSTI)-containing regimens now being considered a preferred option for both initial therapy and switching strategies in virologically suppressed patients, their effects on lymphocyte phenotypes and functions in the course of effective combination antiretroviral therapy (cART) are still unclear. Thus, we investigated the effect of a 24-week elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) regimen on the T cell compartment and HIV reservoirs in HIV-infected patients switching from a suppressive protease inhibitor-based regimen
Is weak CD4+ gain in the course of suppressive combination antiretroviral therapy for HIV infection a current clinical challenge? A case report and brief review of the literature
No full textBackground: Individuals lacking immune recovery during suppressive cART will still represent a clinical issue in the years to come, given the high proportion of HIV-infected subjects introducing therapy late in the course of disease. Understanding the mechanisms underlying poor CD4+ T-cell gain is crucial for the correct clinical management of individuals in this context.
Case presentation: An HIV-infected subject with poor CD4+ T-cell gain in the course of suppressive antiretroviral therapy was extensively investigated to identify the mechanisms behind inadequate CD4+ reconstitution. In particular, we studied the phenotype of circulating T-cells, interleukin-7 signaling in peripheral blood and bone marrow, gut function and microbial translocation markers as well as the composition of the faecal microbiota. Numerous therapeutic interventions ranging from antiretroviral therapy intensification to immunotherapy and anti-hepatitis C virus treatment were also employed in order to target the possible causes of poor immune-recovery.
Conclusions: Poor CD4+ T-cell gain on suppressive antiretroviral therapy is multifactorial and thus represents a clinical challenge. Clinicians should investigate subjects' immune profile as well as possible causes of chronic antigenic stimulation for the administration of the most appropriate therapeutic strategies in this setting
Novel mitochondrial protein interactors of immunoglobulin light chains causing heart amyloidosis
No full textIn immunoglobulin (Ig) light-chain (LC) (AL) amyloidosis, AL deposition translates into life-threatening cardiomyopathy. Clinical and experimental evidence indicates that soluble cardiotoxic LCs are themselves harmful for cells, by which they are internalized. Hypothesizing that interaction of soluble cardiotoxic LCs with cellular proteins contributes to damage, we characterized their interactome in cardiac cells. LCs were purified from patients with AL amyloidosis cardiomyopathy or multiple myeloma without amyloidosis (the nonamyloidogenic/noncardiotoxic LCs served as controls) and employed at concentrations in the range observed in AL patients' sera. A functional proteomic approach, based on direct and inverse coimmunoprecipitation and mass spectrometry, allowed identifying LC-protein complexes. Findings were validated by colocalization, fluorescence lifetime imaging microscopy (FLIM)-fluorescence resonance energy transfer (FRET), and ultrastructural studies, using human primary cardiac fibroblasts (hCFs) and stem cell-derived cardiomyocytes. Amyloidogenic cardiotoxic LCs interact in vitro with specific intracellular proteins involved in viability and metabolism. Imaging confirmed that, especially in hCFs, cardiotoxic LCs (not controls) colocalize with mitochondria and spatially associate with selected interactors: mitochondrial optic atrophy 1-like protein and peroxisomal acyl-coenzyme A oxidase 1 (FLIM-FRET efficiencies 11 and 6%, respectively). Cardiotoxic LC-treated hCFs display mitochondrial ultrastructural changes, supporting mitochondrial involvement. We show that cardiotoxic LCs establish nonphysiologic protein-protein contacts in human cardiac cells, offering new clues on the pathogenesis of AL cardiomyopathy.-Lavatelli, F., Imperlini, E., Orrù, S., Rognoni, P., Sarnataro, D., Palladini, G., Malpasso, G., Soriano, M. E., Di Fonzo, A., Valentini, V., Gnecchi, M., Perlini, S., Salvatore, F., Merlini, G. Novel mitochondrial protein interactors of immunoglobulin light chains causing heart amyloidosis
ORIGINAL RESEARCH Light Chain Amyloidosis: Patient Experience Survey from the Amyloidosis Research Consortium
No full textThe Author(s) 2015. This article is published with open access at Springerlink.com Introduction: Information detailing the experience of patients with light chain (AL) amyloidosis is lacking. The primary aim of this study was to gather data on the patient experience to understand the challenges i
Phillipsite at high pressure: a single-crystal X-ray synchrotron diffraction study
No full textPhillipsite is a low Si/Al natural zeolite, often found as autogenic mineral in both “close” and “open” hydrologic system or in vugs of basalt, as an alteration product of volcanic glass. Along with laumontite, it is one of the most common zeolites found in oceanic basalts. In order to investigate the high-pressure behavior of phillipsite and its structural evolution at the atomic scale, we performed an in situ single-crystal synchrotron X-ray diffraction experiment up to 10 GPa with a diamond anvil cell, using a nominally penetrating pressure-transmitting fluid (methanol:ethanol:H2O = 16:3:1 mix) (Gatta, 2010). The unit-cell parameters and the structure refinements within the P-range investigated show that: 1) phillipsite does not adsorb further H2O molecules from the penetrating-transmitting fluid within the P-range investigated; 2) the configuration of the extra-framework population changes with pressure (between 2 and 3 GPa), affecting the elastic behavior of the mineral. More in details, two distinct compressional regimes have been observed, in which the bulk moduli differs drastically (i.e., KV = 89(8) GPa between 0 and 2 GPa, KV = 18.8(7) GPa between 3 and 9 GPa); 3) phillipsite is crystalline at least up to 10 GPa, and this is surprising if we consider its microporous nature; 4) all the P-induced effects are completely reversible in decompression. The structural refinements allowed us to describe the mechanisms, at the atomic scale, that govern its elastic behavior, which are mainly governed by inter-tetrahedral tilting. The relatively low compressibility of phillipsite at room-P and its relatively wide P-stability shown in this experiment suggests that this zeolite is a potential H2O carrier during the first phase of the oceanic crust subduction or, toward the industrial front, its potential
use in systems for the mechanical energy storage/dissipation (Eroshenko et al., 2001; Soulard et al., 2004).
Acknowledgements: The author acknowledges the Italian Ministry of Education, MIUR-Project: “Futuro in
Ricerca 2012 - ImPACT- RBFR12CLQD”
Unraveling the molecular basis of cardiotoxicity in immunoglobulin light chain amyloidosis.
No full textMicrobial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4(+) cell count
No full textSequencing of bacterial microflora in peripheral blood: our experience with HIV-infected patients
No full textThe healthy gastrointestinal tract is physiologically colonized by a large variety of commensal microbes that influence the development of the humoral and cellular mucosal immune system. Microbiota is shielded from the immune system via a strong mucosal barrier. Infections and antibiotics are known to alter both the normal gastrointestinal tract barrier and the composition of resident bacteria, which may result in possible immune abnormalities. HIV causes a breach in the gastrointestinal barrier with progressive failure of mucosal immunity and leakage into the systemic circulation of bacterial bioproducts, such as lipopolysaccharide and bacterial DNA fragments, which contribute to systemic immune activation. Microbial translocation is implicated in HIV/AIDS immunopathogenesis and response to therapy. We aimed to characterise the composition of bacteria translocating in peripheral blood of HIV-infected patients. To pursue our aim we set up a PCR reaction for the panbacteric 16S ribosomial gene followed by a sequencing analysis. Briefly, whole blood from both HIV-infected and healthy subjects is used. Given that healthy individuals present normal intestinal homeostasis no translocation of microflora is expected in these patients. Following whole blood collection by venipuncture and plasma separation, DNA is extracted from plasma and used to perform a broad range PCR reaction for the panbacteric 16S ribosomial gene. Following PCR product purification, cloning and sequencing analyses are performed
Role of In Vitro Stimulation with Lipopolysaccharide on T-Cell Activation in HIV-Infected Antiretroviral-Treated Patients
No full textWe investigated the effect of LPS in vitro stimulation on T-cell activation in HIV-infected patients with different CD4+ recovery on HAART. PBMCs from 30 HIV-positive, HAART-treated, aviremic individuals with different CD4+ reconstitution (Low Responders: CD4+ < 350/μL; Intermediate Responders: CD4+ 350–599/μL; High Responders: CD4+ ≥ 600/μL) were cultured with LPS and the proportion of HLA-DR/CD38- and Ki67-expressing CD4+/CD8+ T-cells was measured (flow cytometry). Upon LPS stimulation, significantly higher CD4+ and CD8+HLA-DR+ cells were shown in LR and IR versus HIV-negative controls. While no differences in the proportion of LPS-stimulated CD4+CD38+ cells were recorded amongst HIV-positive subgroups, CD8+CD38+ cells were more elevated in patients with lower CD4+ recovery on HAART (i.e., LR and IR). Upon in vitro LPS stimulation, HLA-DR and CD38 expression on T-cells are differentially regulated. While HLA-DR induction reflects impaired CD4+ reconstitution on HAART, cell-surface CD38 expression is increased only on CD8+ T-cells, allowing to speculate that the sole induction of CD38 on CD4+ cells may not be sufficient to depict LPS-driven immune activation in HIV
C-Finite Sequences and Riordan Arrays
No full textMany prominent combinatorial sequences, such as the Fibonacci, Lucas, Pell, Jacobsthal and Tribonacci sequences, are defined by homogeneous linear recurrence relations with constant coefficients. These sequences are often referred to as C-finite sequences, and a variety of representations have been employed throughout the literature, largely influenced by the author’s background and the specific application under consideration. Beyond the representation through recurrence relations, other approaches include those based on generating functions, explicit formulas, matrix exponentiation, the method of undetermined coefficients and several others. Among these, the generating function approach is particularly prevalent in enumerative combinatorics due to its versatility and widespread use. The primary objective of this work is to introduce an alternative representation grounded in the theory of Riordan arrays. This representation provides a general formula expressed in terms of the vectors of constants and initial conditions associated with any recurrence relation of a given order, offering a new perspective on the structure of such sequences
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