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E Ferrero

Publications and source records attributed to E Ferrero.

At least 19 recordsLinked to original sources
PubMed2006

HESS observations of the galactic center region and their possible dark matter interpretation.

The detection of gamma rays from the source HESS J1745-290 in the Galactic Center (GC) region with the High Energy Spectroscopic System (HESS) array of Cherenkov telescopes in 2004 is presented. After subtraction of the diffuse gamma-ray emission from the GC ridge, the source is compatible with a point source with spatial extent less than 1.2;{'}(stat) (95% C.L.). The measured energy spectrum above 160 GeV is compatible with a power law with photon index of 2.25+/-0.04(stat)+/-0.10(syst) and no significant flux variation is detected. It is finally found that the bulk of the very high energy emission must have non-dark-matter origin.

Journal Article↗
PubMed2006

Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Journal Article↗
PubMed2005

Posthemipelvectomy hernia.

We report the case of a white male who underwent a classic hemipelvectomy due to a femur fibrosarcoma with inguinal metastases, which 33 years later, developed into a posthemipelvectomy hernia in the amputation stump that impaired the use of his Canadian prosthesis. The hernia was repaired with a polypropylene mesh in a subaponeurotic position. A seroma was drained in the postoperative and it was only 2 months after the operation that he could use his prosthesis with any difficulty. A year after the operation, the hernia had not recurred. Only seven similar cases have been published, and there are only four cases with details of their correction, two with a mesh as was our case, and the rest with a primary suture of the aponeurotic borders. A brief review of the bibliography is given on this subject.

Femoral Neoplasms↗
PubMed2005

Cardiac risk assessment of asymptomatic patients by stress echocardiography before infrarenal aortic aneurysm surgery.

AIM: Aggressive cardiac assessment before aortic abdominal aneurysm (AAA) surgery is indicated for patients with symptomatic coronary artery disease (CAD). Assessment of intermediate and moderate risk patients is still under debate. The purpose of the study was to prospectively evaluate the effectiveness of stress echocardiography (SE) in the detection of CAD in patients undergoing AAA surgery who have no symptoms and/or signs of CAD, but who have risk factors for it. METHODS: Patients with 1 or more risk factors for CAD underwent SE. All patients with positive SE underwent coronary arteriography, and, when indicated, treatment. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for SE by comparing results to coronary arteriography. Moreover, major perioperative cardiac events were recorded. RESULTS: Ninety-one patients with AAA and risk factors for CAD were studied. SE was positive in 9 cases, including 7 presenting critical CAD on the basis of coronary arteriography. One major cardiac event (1.1%), a nonfatal myocardial infarction, occurred in 1 patient with positive SE and non-critical, single-vessel CAD. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SE proved to be 100%, 98%, 78%, 100%, and 92%, respectively. CONCLUSIONS: Positive SE should be considered a valid method for testing high-risk patients for CAD. The low rate of major cardiac events in this series suggests that cardiac assessment by SE and selective coronary arteriography prior to AAA surgery is effective in asymptomatic patients with one or more risk factors.

Aged↗
PubMed2003

Live liver donation: a prospective analysis of exclusion criteria for healthy and potential donors.

INTRODUCTION: Living donor liver transplantation represents a controversial option to increase the donor pool. DESIGN: Prospective and descriptive clinical study. OBJECTIVE: (1) To identify risk factors (exclusion criteria) for live donation; (2) to determine the rate of recipients that benefit from a living donor. METHODS: Between May 1995 (first adult-to-adult living donor liver transplantation in Spain) and November 2002, we evaluated 74 healthy volunteers and performed 12 living donor liver transplants (no donor mortality). RESULTS: All actual donors and volunteers are alive and healthy. After a mean time of 3.2+/-0.5 weeks, 72% of potential donors were considered unsuitable for live donation. Exclusion criteria were grouped in three categories: (primary) donor safety reasons (68%); (secondary): ABO mismatch (17%) and (tertiary): cadaveric graft transplantation (15%). Consequently, just 43.7% of the recipients presenting to us with a potential living donor, did finally benefit from these organs. The mortality rate was 8.3% for 43 recipients presenting with a living donor in comparison to 15% for those who did not (321 recipients between May 1995 and November 2001). CONCLUSIONS: ALDLT can benefit a significant number of recipients on the waiting list (43.7% of those presenting with a donor). The most frequent exclusion criteria concern donor safety, namely, unsuspected chronic liver diseases and unsuspected thrombophilic disorders.

ABO Blood-Group System↗
PubMed2002

Regulation of endothelial cell shape and barrier function by chromogranin A.

We have found that chromogranin A (CgA), a protein released in circulation by neuroendocrine cells and neurons, prevents the vascular leakage induced by tumor necrosis factor (TNF) in a mouse model. Studies of the mechanism of action showed that CgA and its NH(2)-terminal fragments inhibit TNF-induced vascular permeability by preventing endothelial cytoskeleton rearrangements. We propose that neuronal/endocrine secretion of CgA could contribute to the regulation of endothelial barrier function and the protection of vessels against plasma leakage in inflammatory diseases.

Animals↗
PubMed2001

Roles of tumor necrosis factor p55 and p75 receptors in TNF-alpha-induced vascular permeability.

We have investigated the role of p55 and p75 tumor necrosis factor receptors 1 and 2 (TNFR1 and TNFR2, respectively) in TNF-induced alteration of endothelial permeability in vitro and in vivo. Stimulation of TNFR1 with an agonist antibody or a receptor-selective TNF mutein increased the flux of (125)I-albumin through endothelial cell monolayers. An antagonist anti-TNFR1 antibody, but not antagonist anti-TNFR2 antibodies, blocked the activity of TNF in vitro. Stimulation of TNFR1, but not TNFR2, induced cytoskeletal reorganization associated with increased permeability. SB-203580, a p38 mitogen-activated protein kinase inhibitor, blocked TNFR1-induced cytoskeletal reorganization and permeability. A selective mouse TNFR1 agonist and human TNF, which binds to murine TNFR1, increased the leakage of trypan blue-albumin from liver vessels in mice. These results indicate that stimulation of TNFR1 is necessary and sufficient to increase endothelial permeability in vitro and in vivo. However, an antagonist anti-murine TNFR2 antibody partially inhibited the effect of murine TNF on liver vessels, suggesting that TNFR2 also plays a role in the regulation of TNF-induced vascular permeability in vivo.

Animals↗
PubMed2000

uPA/uPAR system is active in immature dendritic cells derived from CD14+CD34+ precursors and is down-regulated upon maturation.

We recently described a subset of peripheral CD14+CD34+ cells able to migrate across endothelial cell monolayers and differentiate into immunostimulatory dendritic cells (DC). In this paper we show that immature DC derived from CD14+CD34+ precursors are also capable of reverse transendothelial migration and extracellular matrix (ECM) invasion using the urokinase plasminogen activator receptor (uPAR). We found that these cells respond to macrophage-inflammatory protein (MIP)-1alpha, enhancing their ability to invade ECM and supporting the idea that immature DC are selectively recruited at the site of inflammation to expand the pool of APCs. Interestingly, MIP-1alpha was also capable of preventing the decreased matrix invasion observed by blocking uPAR, suggesting that the uPA/uPAR system and MIP-1alpha cooperate in driving immature DC migration through the subendothelial matrix. Upon exposure to maturating stimuli, such as TNF-alpha, CD14+CD34+-derived DC enhance their APC function and decrease the capacity of invading ECM; these changes are accompanied by altered expression and function of uPAR. Moreover, mature DC shift their sensitivity from MIP-1alpha to MIP-3beta, enhancing their transendothelial migration capability in response to the latter chemokine. Our data support the hypothesis that bloodborne DC can move through ECM toward the site of pathogen entry where they differentiate into fully mature APCs with their motility and function regulated by microenvironmental stimuli, including MIP-1alpha, MIP-3beta, and TNF-alpha.

Antigens, CD34↗
PubMed1999

IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V delta 2+ TCR gamma delta+ T lymphocytes from healthy donors and multiple sclerosis patients.

Gamma delta T lymphocytes are thought to play a role in the pathogenesis of multiple sclerosis (MS) contributing to demyelinization and fibrosis in the central nervous system. In this study, we show that, in MS patients with active disease, the percentage of circulating V delta 2+ gamma delta T cells coexpressing NKRP1A is significantly increased compared with healthy donors. V delta 2+ and V delta 1+ T cells were sorted from MS patients and healthy volunteers and cloned. At variance with V delta 1+ clones, all V delta 2+ clones expressed NKRP1A, which was strongly up-regulated upon culture with IL-12; this effect was neutralized by specific anti-IL-12 Abs. No up-regulation of NKRP1A by IL-12 was noted on V delta 1+ clones. RNase protection assay showed that IL-12R beta 2 subunit transcript was significantly less represented in V delta 1+ than V delta 2+ clones. This finding may explain the different effect exerted by IL-12 on these clones. In transendothelial migration assays, V delta 2+ NKRP1A+ clones migrated more effectively than V delta 1+ clones, and this migratory potential was enhanced following culture with IL-12. Migration was strongly inhibited by the F(ab')2 of an anti-NKRP1A Ab, suggesting that this lectin is involved in the migration process. We also show that, in freshly isolated PBMC from MS patients, the migrated population was enriched for V delta 2+ NKRP1A+ cells. We conclude that the expression of NKRP1A on V delta 2+ cells is associated with increased ability to migrate across the vascular endothelium and that this phenomenon may be regulated by IL-12 present in the microenvironment.

Adjuvants, Immunologic↗
PubMed1999

The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38.

Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of expression in leukocytes, although evidence is accumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a member of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nature. Functionally, CD38 is an eclectic molecule with the ability not only to catalyze but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan, and to other ligands. Interaction with CD38 on various leukocyte subpopulations has profound though diverse consequences on their life-span, but these effects seem to be independent of the enzymatic activity of the molecule. CD38 challenges our expectations of a surface molecule and we must sift through its many guises to unmask its true nature.

ADP-ribosyl Cyclase↗
PubMed1999

The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST-1) gene.

CD38 is a leukocyte activation antigen and ectoenzyme [NAD(P)+ glycohydrolase; EC 3.2.2.6] involved in numerous immune functions. The human CD38 gene is complex [eight exons, >80 kilobases (kb) long] located on Chromosome 4p15, and part of the eukaryotic NAD+ glycohydrolase/ADP-ribosyl cyclase gene family. Because of the increasing relevance of the CD38 molecule in the host immune response to infectious, tumoral, and metabolic diseases, we investigated the genetic variability and linkage of the human CD38 locus. We report that (1) the restriction endonuclease Pvu II identifies a bi-allelic polymorphism here defined as formed by the alleles CD38*A (12 kb) and CD38*B (9/2.5 kb); (2) their frequency in the healthy Italian Caucasian population is 14% and 86%, respectively; (3) the polymorphic Pvu II site is located at the 5' end of the first intron of the CD38 gene; (4) in conjunction with the polymorphic site, we identified a 900 base pair CpG island associated with the CD38 gene, with two potential Sp1 binding sites; (5) the CpG island may play a role in the regulation of CD38 expression and is hypomethylated in various cell lines; (6) by pulsed-field gel electrophoresis we show that CD38 and its paralogue, the bone-marrow stromal cell antigen BST-1 (CD157), map to the same 800 kb Avi II fragment, indicating that the two human ecto-NADase genes are closely linked.

ADP-ribosyl Cyclase↗
PubMed1999

Early events in dendritic cell maturation induced by LPS.

Immature dendritic cells (Dcs) are characterised by high antigen uptake ability and poor T-cell stimulatory function. In contrast, mature DCs have a high stimulatory function and poor antigen uptake ability. Inflammatory stimuli induce DC maturation and migration from nonlymphoid tissues to lymphoid organs. We investigated the effect of lipopolysaccharide (LPS) on DC antigen uptake and migratory function at early and late stimulation time points. We observed that the transition from the immature to the mature state is not a progressive itinerary, but it is characterised by precise functional stages. At early time points after LPS stimulation DCs significantly decrease their intrinsic migratory ability and increase the antigen uptake function. Later, around 4 h after LPS activation, DCs show recovery of migratory ability and start to progressively lose their antigen uptake function until the mature stage in which they show poor antigen uptake and migratory activity.

Animals↗
PubMed1998

Endothelial cell E- and P-selectin and vascular cell adhesion molecule-1 function as signaling receptors.

Previous studies have shown that polymorphonuclear leukocyte (PMN) adherence to endothelial cells (EC) induces transient increases in EC cytosolic free calcium concentration ([Ca2+]i) that are required for PMN transit across the EC barrier (Huang, A.J., J.E. Manning, T. M. Bandak, M.C. Ratau, K.R. Hanser, and S.C. Silverstein. 1993. J. Cell Biol. 120:1371-1380). To determine whether stimulation of [Ca2+]i changes in EC by leukocytes was induced by the same molecules that mediate leukocyte adherence to EC, [Ca2+]i was measured in Fura2-loaded human EC monolayers. Expression of adhesion molecules by EC was induced by a pretreatment of the cells with histamine or with Escherichia coli lipopolysaccharide (LPS), and [Ca2+]i was measured in single EC after the addition of mAbs directed against the EC adhesion proteins P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or platelet/endothelial cell adhesion molecule-1 (PECAM-1). Both anti-P- and anti-E-selectin mAb, as well as anti-VCAM-1 mAb, induced transient increases in EC [Ca2+]i that were comparable to those induced by 200 microM histamine. In contrast, no effect was obtained by mAbs directed against the endothelial ICAM-1 or PECAM-1. PMN adherence directly stimulated increases in [Ca2+]i in histamine- or LPS-treated EC. mAbs directed against leukocyte CD18 or PECAM-1, the leukocyte counter-receptors for endothelial ICAM-1 and PECAM-1, respectively, did not inhibit PMN-induced EC activation. In contrast, mAb directed against sialyl Lewis x (sLex), a PMN ligand for endothelial P- and E-selectin, completely inhibited EC stimulation by adherent PMN. Changes in EC [Ca2+]i were also observed after adherence of peripheral blood monocytes to EC treated with LPS for 5 or 24 h. In these experiments, the combined addition of mAbs to sLex and VLA-4, the leukocyte counter-receptor for endothelial VCAM-1, inhibited [Ca2+]i changes in the 5 h-treated EC, whereas the anti-VLA-4 mAb alone was sufficient to inhibit [Ca2+]i changes in the 24 h-treated EC. Again, no inhibitory effect was observed with an anti-CD18 or anti-PECAM-1 mAb. Of note, the conditions that induced changes in EC [Ca2+]i, i.e. , mAbs directed against endothelial selectins or VCAM-1, and PMN or monocyte adhesion to EC via selectins or VCAM-1, but not via ICAM-1 or PECAM-1, also induced a rearrangement of EC cytoskeletal microfilaments from a circumferential ring to stress fibers. We conclude that, in addition to their role as adhesion receptors, endothelial selectins and VCAM-1 mediate endothelial stimulation by adhering leukocytes.

Actins↗
PubMed1998

CD14+ CD34+ peripheral blood mononuclear cells migrate across endothelium and give rise to immunostimulatory dendritic cells.

We describe a subset of peripheral CD14+ cells, coexpressing the CD34 progenitor marker and able to migrate across endothelial cell monolayers. On culture with granulocyte-macrophage-CSF, this population differentiated into dendritic cells expressing CD83, CD80, HLA-DR(bright), CD86, and CD54. These dendritic cells were immunostimulatory, in that they induced proliferation of allogenic and tetanus toxoid-specific T lymphocytes. The CD14+ CD34+ population expressed higher levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and alpha4beta1 integrin than the CD14+ CD34- counterpart, being dull positive for other integrins. Using stably transfected PECAM-1+, VCAM-1+, or ICAM-1+ cells, we found that PECAM-1 and, to a lesser extent, VCAM-1, could support transmigration of CD14+ CD34+ cells, whereas the alphaL-ICAM-1 interaction was involved in cell adhesion. PECAM-1-driven transmigration was conceivably dependent on a haptotactic gradient, as it was reduced by 80% across NIH3T3 cells transfected with the PECAM-1-delta cyto deletion mutant. This mutant lacks the cytoplasmic tail and displays a reduced tendency to localize at the intercellular junctions, thus failing to form a molecular junctional gradient. Once differentiated, dendritic cells derived from CD14+ CD34+ precursors retained their transendothelial migratory capability, using both PECAM-1 and ICAM-1 for transmigration. We suggest that a subset of CD14+ CD34+ circulating leukocytes can localize to peripheral tissues and differentiate into functional dendritic cells, thus representing a functional reservoir of potential APC. PECAM-1, constitutively expressed on vascular endothelium, is likely to play a relevant role in the egress of this population from the bloodstream.

Antigens, CD34↗
PubMed1998

p40/LAIR-1 regulates the differentiation of peripheral blood precursors to dendritic cells induced by granulocyte-monocyte colony-stimulating factor.

p40/LAIR-1, a member of the immunoglobulin superfamily, is a surface molecule broadly distributed among leukocytes which has been shown to down-regulate T and NK cell activation. In this study, we show that p40/LAIR-1 is highly expressed in CD14+ peripheral blood mononuclear cells (PBMC). When cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10-14 days, CD14+ cells acquired morphologic and phenotypic features (i.e. loss of CD14 and expression of CD80bright and CD86bright) typical of dendritic cells (DC) and lost the expression of p40/LAIR-1. Engagement of p40/LAIR-1 (but not of CD58) by specific monoclonal antibodies prevented CD14+ PBMC differentiation into DC; when cultured in the presence of GM- CSF upon p40/LAIR-1 cross-linking, the resulting cells were CD14+CD80(dull)CD86(dull) and displayed a macrophage-like morphology. We have recently demonstrated that peripheral blood CD14+ cells co-expressing the CD34 progenitor marker represent the circulating precursors of CD83+ DC. Herein we show that cross-linking of p40/LAIR-1 prevented the maturation of CD14+CD34+ cells into CD83+ DC. This effect appears to be consequent to the impairment of GM-CSF receptor-mediated activation signaling. Indeed, triggering of GM-CSF receptors in both CD14+ and CD14+CD34+ cells led to increases in the intracellular free calcium concentrations which were inhibited by p40/LAIR-1 engagement. Taken together, these data suggest a possible regulating role played by p40/LAIR-1 in the process of differentiation from peripheral blood precursors into DC induced by GM-CSF.

Calcium↗