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Biomedical subjects

G Schiavoni

Publications and source records attributed to G Schiavoni.

At least 19 recordsLinked to original sources

IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features.

Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1(-/-)) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8alpha(+) subset. IRF-1(-/-) splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-beta, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1(-/-) DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1(-/-) mice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4(+)CD25(+) regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells.

Animals↗

Microbiological indoor air quality in healthy buildings.

There is a growing interest in indoor air quality for a better quality environment both at home and at work because many people spend at least 80% of their time indoors. The aim of our study was to evaluate the indoor concentration of airborne bacteria and fungi in a University auditorium, in an office of public buildings and in an apartment in the presence and in absence of building's occupants, building materials and furnishings. The concentrations of airborne bacteria and fungi were determined using a Surface Air System (SAS). In presence of people and furnishings the average air concentrations of bacteria (University auditorium: 925-1225 CFU m(-3); office: 493 CFU m(-3); apartment: 92-182 CFU m(-3)) were higher than in absence (respectively: 190-315 CFU m(-3); 126 CFU m(-3); 66-80 CFU m(-3)). The average air concentrations fungal were higher in presence of people and furnishings (University auditorium: 1256-1769 CFU m(-3); office: 858 CFU m(-3); apartment: 147-297 CFU m(-3)) than in absence (respectively: 301-431 CFU m(-3); 224 CFU m(-3); 102-132 CFU m(-3)). The obtained data can be considered as a step to identify acceptable levels for bioaerosols in common indoor environments.

Air Pollution, Indoor↗

IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation.

Cytokines that are induced by infection may contribute to the initiation of immune responses through their ability to stimulate dendritic cells (DCs). In this paper, we have addressed the role of IL-15 in DC activation, investigating its expression by DCs in response to three different signals of infection and examining its ability to stimulate DCs. We report that the expression of both IL-15 and the IL-15 receptor alpha-chain are increased in splenic DCs from mice inoculated with dsRNA (poly(I:C)), LPS, or IFN-alphabeta, and in purified murine splenic DCs treated with IFN-alphabeta in vitro. Furthermore, IL-15 itself was able to activate DCs, as in vivo or in vitro exposure of splenic DCs to IL-15 resulted in an up-regulation of costimulatory molecules, markedly increased production of IFN-gamma by DC and an enhanced ability of DCs to stimulate Ag-specific CD8(+) T cell proliferation. The magnitude of all of the IL-15-induced changes in DCs was reduced in mice deficient for the IFN-alphabeta receptor, suggesting a role for IFN-alphabeta in the stimulation of DCs by IL-15. These results identify IL-15 as a stimulatory cytokine for DCs with the potential for autocrine activity and link its effects to expression of IFN-alphabeta.

Adjuvants, Immunologic↗

Prevalence of Chlamydia pneumoniae in peripheral blood mononuclear cells in Italian patients with acute ischaemic heart disease.

Chlamydia pneumoniae infection generally starts in the respiratory tract and probably disseminates systemically in the blood stream within alveolar macrophages. We investigated the prevalence of C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) in patients with acute ischaemic heart disease. Samples of blood were obtained from 93 consecutive patients with acute ischaemic heart disease and from 42 healthy subjects, for detection of C. pneumoniae DNA in PBMC by polymerase chain reaction (PCR) and for serology. C. pneumoniae DNA in PBMC was detected in 25.8% (24/93) of the patients with acute ischaemic heart disease and in 4.8% (2/42) of the healthy subjects (P=0.008). C. pneumoniae IgG was found in 76.3% of patients and in 45.2% of healthy subjects (P=0.0008) while C. pneumoniae IgA was found in 59.1% and in 33.3%, respectively (P=0.01). No correlation was found between anti-C. pneumoniae antibody titers and positive PCR results. The detection of C. pneumoniae DNA in PBMC may aid in selecting patients who may benefit from antibiotic treatment; however, to support this contention, longitudinal studies on patients treated with antibiotics would also be necessary.

Aged↗

Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo.

Type I interferons (IFN-I) are rapidly induced following infection and play a key role in nonspecific inhibition of virus replication. Here we have investigated the effects of IFN-I on the generation of antigen-specific antibody responses. The data show that IFN-I potently enhance the primary antibody response to a soluble protein, stimulating the production of all subclasses of IgG, and induce long-lived antibody production and immunological memory. In addition, endogenous production of IFN-I was shown to be essential for the adjuvant activity of CFA. Finally, IFN-I enhanced the antibody response and induced isotype switching when dendritic cells were the only cell type responding to IFN-I. The data reveal the potent adjuvant activity of IFN-I and their important role in linking innate and adaptive immunity.

Adjuvants, Immunologic↗

Cyclophosphamide induces type I interferon and augments the number of CD44(hi) T lymphocytes in mice: implications for strategies of chemoimmunotherapy of cancer.

In a previous study, we reported that a single injection of cyclophosphamide (CTX) in tumor-bearing mice resulted in tumor eradication when the animals were subsequently injected with tumor-sensitized lymphocytes. Notably, CTX acted by inducing bystander effects on T cells, and the response to the combined CTX/adoptive immunotherapy regimen was inhibited in mice treated with antibodies to mouse interferon (IFN)-alpha/beta. In the present study, we have investigated whether CTX induced the expression of type I IFN, and we have characterized the CTX effects on the phenotype of T cells in normal mice. CTX injection resulted in an accumulation of type I IFN messenger RNA in the spleen of inoculated mice, at 24 to 48 hours, that was associated with IFN detection in the majority of the animals. CTX also enhanced the expression of the Ly-6C on spleen lymphocytes. This enhancement was inhibited in mice treated with anti-type I IFN antibodies. Moreover, CTX induced a long-lasting increase in in vivo lymphocyte proliferation and in the percentage of CD44(hi)CD4(+) and CD44(hi)CD8(+ )T lymphocytes. These results demonstrate that CTX is an inducer of type I IFN in vivo and enhances the number of T cells exhibiting the CD44(hi) memory phenotype. Since type I IFN has been recently recognized as the important cytokine for the in vivo expansion and long-term survival of memory T cells, we suggest that induction of this cytokine may explain at least part of the immunomodulatory effects observed after CTX treatment. Finally, these findings provide a new rationale for combined treatments with CTX and adoptive immunotherapy in cancer patients. (Blood. 2000;95:2024-2030)

Animals↗

Ticlopidine and aspirin fail to suppress the increased platelet aggregability that follows percutaneous coronary interventions.

Previous studies indicate that percutaneous transluminal coronary angioplasty (PTCA) is associated with platelet activation. It is not well-established whether enhanced platelet aggregability after PTCA is prevented by the association of ticlopidine with aspirin. The aim of this study was to evaluate whole blood platelet aggregability before and after elective PTCA in patients with chronic stable angina receiving ticlopidine and aspirin. We studied 16 patients referred for elective PTCA, treated for > or = 72 hours with oral aspirin and ticlopidine (group 1), and 10 patients referred for diagnostic coronary angiography, treated with oral aspirin alone (group 2). An intravenous bolus of heparin was administered at the start of PTCA. In both groups, platelet aggregability was assessed at baseline and 24 hours after the procedure, using the PFA 100(R) system. This method measures the time required for flowing whole blood to occlude a collagen and adenosine diphosphate (ADP)-coated ring, shorter times indicating greater aggregability. In both groups, platelet aggregability after the procedure was significantly increased compared with baseline: 104+/-30 seconds before versus 88+/-24 seconds at 24 hours in group 1 (p=0.03) and 84+/-16 seconds before versus 69+/-14 seconds at 24 hours in group 2 (p=0.004). Group 1 patients, compared with group 2, showed a trend toward reduced aggregability at baseline (p=0.06) and significantly lower aggregability 24 hours after the procedure (p=0.03). Ticlopidine and aspirin reduce whole-blood platelet aggregability compared with aspirin alone but fail to suppress the increased aggregability that occurs 24 hours after PTCA.

Aged↗

Midterm endothelial function and remodeling of radial artery grafts anastomosed to the aorta.

BACKGROUND: The purpose of this study was to elucidate the midterm endothelium-dependent vasodilatory capacity of radial artery grafts anastomosed to the aorta, as well as their morphometric evolution with the time. METHODS: Five years after surgery we evaluated the response of aorta-anastomosed radial artery grafts to the endovascular infusion of acetylcholine in 11 of the first 61 patients operated on at our institution, and we compared it to the response with that of internal thoracic artery grafts. Moreover, the first 20 patients who had a perfect radial artery graft on angiography at 1 year were restudied at 5 years and subjected to a comparative analysis of the diameters of the radial artery graft and the grafted coronary arteries. RESULTS: At midterm angiography, dilation of the 2 types of grafts was similar in response to acetylcholine administration (radial artery, from 2.61 +/- 0.39 to 2. 90 +/- 0.34 mm; internal thoracic artery, from 2.68 +/- 0.21 to 2.93 +/- 0.27 mm; P =.01 for both). The diameters of aorta-anastomosed radial artery grafts and grafted coronary arteries increased between both 1 and 5 years according to angiographic studies (radial artery grafts, from 2.08 +/- 0.45 to 2.54 +/- 0.53 mm; grafted coronary arteries, from 1.92 +/- 0.47 to 2.18 +/- 0.41 mm; P <.001 for both), but the increase was greater for the radial artery grafts (P <.001). CONCLUSIONS: Aorta-anastomosed radial artery grafts maintain an appreciable capacity for endothelium-dependent vasodilatation 5 years after implantation and undergo a progressive increase in luminal diameter with time. These observations contradict the presumed tendency for progressive fibrous intimal hyperplasia to develop in radial artery grafts.

Acetylcholine↗

Reversible left anterior descending artery spasm, prolonged cardiac arrest and left main thrombosis during a PTCA attempt of the circumflex artery.

The authors report a case of percutaneous transluminal coronary angioplasty of the circumflex artery complicated by occlusion of the non-diseased left anterior descending artery by spasm. During advanced cardiac life support, required for the subsequent cardiac arrest, intra-coronary nitrates and calcium antagonists were administered. After 45 minutes, the spasm resolved, but N probably as a result of prolonged blood stasis N a thrombus appeared in the left main artery. While attempting to stent the left main, the thrombus was mechanically dislodged, leaving the epicardial coronary tree free, with a good flow.

Angioplasty, Balloon, Coronary↗

Biofilm formation on the surface of ceramic tiles.

The aim of the study was to investigate the formation of biofilm on the surface of ceramic tiles, widely present in public and private buildings, using six parallel flow chambers. Our flow system was conceived and made to compare biofilm results by parallel distributed rectangular tiles. The tiles, divided into two identical A and B sections, were placed within the flow chambers. Biofilm formation was performed after 72 h and was quantified by viable counts of bacteria. Average viable counts ranged from 1.1x10(7) to 7.3x10(7) cfu cm(-2) and from 1.1x10(7) to 5.8x10(7) cfu cm(-2) respectively for biofilm A and B sections. As statistical analysis does not show significant differences, we can conclude that biofilms obtained were so similar to each other that they confirmed the system reproducibility. Our next step will be to use our system to study Legionella pneumophila and to evaluate the efficacy of antibacterial agents.

Biofilms↗

[Remodelling of the radial artery graft 5 years after aortocoronary bypass intervention].

BACKGROUND: The radial artery (RA) is being employed as coronary artery bypass graft with good results, but when it is proximally anastomosed to the ascending aorta, undergoes substantial hemodynamic changes which could lead to significant graft intimal hyperplasia. The aim of this study was to investigate the evolution of RA graft morphology over time. METHODS: We studied 20 patients with a perfectly patent RA graft at both 1 and 5 year angiography after coronary artery bypass graft. RESULTS: Both RA graft and grafted coronary artery diameters, assessed by quantitative coronary angiography, significantly increased at 5 years, in comparison to 1 year angiography (2.08 +/- 0.45 vs 2.54 +/- 0.53 mm, +22%, p < 0.001 and 1.92 +/- 0.47 vs 2.18 +/- 0.41 mm, +13.3%, p < 0.001, respectively). CONCLUSIONS: Hemodynamic changes following RA employment for coronary artery bypass graft stimulate a remodeling of RA graft itself and of the grafted coronary arteries. The progressive increase of diameters observed in RA grafts strongly argues against the development of flow-limiting graft intimal hyperplasia when RA is proximally anastomosed to the ascending aorta. Moreover, grafted coronary artery dilation suggests that hemorrheologic changes following coronary artery bypass graft could play a major role in the development of RA remodeling over time.

Analysis of Variance↗

Rhythm of carnitine levels in serum and urine of normal subjects.

A study of the diurnal serum and urine levels of L-carnitine and acetylcarnitine was carried out in eleven healthy volunteers. No significant difference was found between the levels in the morning and in the afternoon, although a higher carnitinaemia was shown in the waking hours when the energy demands were higher.

Acetylcarnitine↗