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Showing papers by "University of Perugia published in 2005"


Journal ArticleDOI
TL;DR: Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified; mortality rates from heart failure did not differ between groups.

3,899 citations


Journal ArticleDOI
TL;DR: Cytoplasmic NPM is a characteristic feature of a large subgroup of patients with AML who have a normal karyotype, NPM gene mutations, and responsiveness to induction chemotherapy.
Abstract: Background Nucleophosmin (NPM), a nucleocytoplasmic shuttling protein with prominent nucleolar localization, regulates the ARF-p53 tumor-suppressor pathway. Translocations involving the NPM gene cause cytoplasmic dislocation of the NPM protein. Methods We used immunohistochemical methods to study the subcellular localization of NPM in bone marrow–biopsy specimens from 591 patients with primary acute myelogenous leukemia (AML). We then correlated the presence of cytoplasmic NPM with clinical and biologic features of the disease. Results Cytoplasmic NPM was detected in 208 (35.2 percent) of the 591 specimens from patients with primary AML but not in 135 secondary AML specimens or in 980 hematopoietic or extrahematopoietic neoplasms other than AML. It was associated with a wide spectrum of morphologic subtypes of the disease, a normal karyotype, and responsiveness to induction chemotherapy, but not with recurrent genetic abnormalities. There was a high frequency of FLT3 internal tandem duplications and absen...

1,718 citations


Journal ArticleDOI
TL;DR: The mismatched-related transplant emerges as a viable, alternative source of stem cells for acute leukemia patients without matched donors and/or those who urgently need transplantation.
Abstract: Purpose Establishment of hematopoietic stem-cell (HSC) transplantation from mismatched relatives is feasible for patients with acute leukemia. As our original method of graft processing was unsuitable for large-scale clinical studies, we use automated devices for CD34+ cell purification. Patients and Methods Sixty-seven patients with acute myeloid leukemia (AML; 19 complete remission [CR] 1, 14 CR 2, nine CR > 2, 25 in relapse) and 37 with acute lymphoid leukemia (ALL; 14 CR 1, eight CR 2, two CR > 2, 13 in relapse) were conditioned with total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin. Peripheral-blood progenitor cells were mobilized with recombinant human granulocyte colony-stimulating factor and depleted of T-cells using CD34+ cell immunoselection. No post-transplantation graft-versus-host disease (GvHD) prophylaxis was administered. Results Primary engraftment was achieved in 94 of 101 assessable patients. Six of the seven patients who rejected the primary graft, engrafted aft...

677 citations


Journal ArticleDOI
TL;DR: Evidence of oxidative stress in aging brain, some of the most important neurodegenerative diseases, and in two common and highly disabling vascular pathologies--stroke and cardiac failure are reviewed.

633 citations


Journal ArticleDOI
01 Jun 2005-Carbon
TL;DR: In this article, uniform dispersion of single-walled carbon nanotubes (SWNTs) in isotactic polypropylene (iPP) was achieved by shear mixing.

581 citations


Journal ArticleDOI
TL;DR: Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia.
Abstract: Background The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. Methods We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). Results An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, –20 percent; 95 percent confidence interval, –26 to –14 percent; P=0.001). The levofloxacin group had a lower rate of microbiological...

566 citations


Journal ArticleDOI
TL;DR: High‐intensity warfarin was not superior to standard treatment in preventing recurrent thrombosis in patients with APS and was associated with an increased rate of minor hemorrhagic complications.

515 citations


Journal ArticleDOI
TL;DR: Dental pulp is an easily accessible and efficient source of MSCs, with different kinetics and differentiation potentialities from MSCS as isolated from the bone marrow, and the rapid proliferative capacity together with the immunoregulatory characteristics of DP-MSCs may prompt future studies aimed at using these cells in the treatment or prevention of T-cell alloreactivity in hematopoietic or solid organ allogeneic transplantation.
Abstract: Background Bone marrow mesenchymal stem cells (MSCs) are currently being investigated in preclinical and clinical settings because of their multipotent differentiative capacity or, alternatively, their immunosuppressive function. The aim of this study was to evaluate dental pulp (DP) as a potential source of MSCs instead of bone marrow (BM). Methods Flow cytometric analysis showed that DP-MSCs and BM-MSCs were equally SH2, SH3, SH4, CD29 and CD 166 positive. The in vitro proliferative kinetics of MSCs were measured by 3H-thymidine incorporation uptake. The immunosuppressive function of MSCs was then tested by coculturing PHA-stimulated allogeneic T cells with or without MSCs for 3 days. Results BM-MSCs could be differentiated in vitro into osteogenic, chondrogenic and adipogenic lineages. DP-MSCs showed osteogenic and adipocytic differentiation, but did not differentiate into chondrocytes. Although DP-MSCs grow rapidly in vitro between day 3 and day 8 of culture and then decrease their proliferation by day 15, BM-MSCs have a stable and continuous proliferation over the same period of time. The addition of DP-MSCs or BM-MSCs resulted in 91 +/- 4% and 75 +/- 3% inhibition of T cell response, respectively, assessed by a 3H-thymidine assay. Conclusions Dental pulp is an easily accessible and efficient source of MSCs, with different kinetics and differentiation potentialities from MSCs as isolated from the bone marrow. The rapid proliferative capacity together with the immunoregulatory characteristics of DP-MSCs may prompt future studies aimed at using these cells in the treatment or prevention of T-cell alloreactivity in hematopoietic or solid organ allogeneic transplantation.

508 citations


Journal ArticleDOI
TL;DR: Several AIRDs exhibit increased overt cardiovascular disease (CVD) prevalence as well as findings of advanced subclinical atherosclerosis, which may precede the appearance of a clinical disease and thus be a target of early identification and preventive therapy.
Abstract: Received October 16, 2004; revision received June 4, 2005; accepted June 7, 2005 Atherosclerosis is a multifactorial process that commences in childhood but manifests clinically later in life Atherosclerosis is increasingly considered an immune system–mediated process of the vascular system The presence of macrophages and activated lymphocytes within atherosclerotic plaques supports the concept of atherosclerosis as an immune system–mediated inflammatory disorder1,2 Inflammation can aggravate atherosclerosis via different mechanisms secondary to autoimmunity, infectious diseases, and other proatherogenic changes that occur during the inflammatory state Autoimmune rheumatic diseases (AIRDs) are associated with higher rates of cardiovascular morbidity and mortality, primarily secondary to accelerated atherosclerosis This phenomenon can be attributed to traditional risk factors for atherosclerosis and use of specific drugs, such as corticosteroids, but also might be the result of other autoimmune and inflammatory mechanisms that are aggravated in AIRDs Several AIRDs exhibit increased overt cardiovascular disease (CVD) prevalence as well as findings of advanced subclinical atherosclerosis, which may precede the appearance of a clinical disease and thus be a target of early identification and preventive therapy Cells of the immune system can be found within atherosclerotic plaques, which suggests that they have a role in the atherogenic process Their migration and activation within the plaques can be secondary to various stimuli, including infectious agents3 These cells probably aggravate atherosclerosis, because CD4+ and CD8+ T-cell depletion reduced fatty streak formation in C57BL/6 mice In addition, after crossing of apolipoprotein E (ApoE)-knockout mice with immunodeficient scid/scid mice, the offspring had a 73% reduction in aortic fatty streak lesions compared with the immunocompetent apoE mice Moreover, when CD4+ T cells were transferred from the immunocompetent to the immunodeficient mice, they increased lesion area in the latter by 164%4 It is therefore not surprising that as in autoimmune diseases, the cellular components …

506 citations


Journal ArticleDOI
TL;DR: In conclusion, CSE‐derived H2S is involved in the maintenance of portal venous pressure and the reduction of CSE expression in the liver with cirrhosis contributes to the development of increased intrahepatic resistance and portal hypertension.

503 citations




Journal ArticleDOI
TL;DR: These data establish a physiologic role for H(2)S in regulating the gastric microcirculation and identify CSE as a novel target for ASA/NSAIDs.

Journal ArticleDOI
TL;DR: It is concluded that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative Stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

Journal ArticleDOI
15 Dec 2005-Blood
TL;DR: Large numbers of donor T-cell clones specific for Aspergillus or cytomegalovirus antigens were generated and identified clones potentially responsible for causing GvHD by screening them for cross-reactivity against recipient mononuclear cells.

Journal ArticleDOI
23 Dec 2005-Science
TL;DR: Data from the northern lowlands of Chryse Planitia have revealed a shallowly buried quasi-circular structure about 250 kilometers in diameter that is interpreted to be an impact basin and a planar reflector associated with the basin structure may indicate the presence of a low-loss deposit that is more than 1 kilometer thick.
Abstract: The martian subsurface has been probed to kilometer depths by the Mars Advanced Radar for Subsurface and Ionospheric Sounding instrument aboard the Mars Express orbiter. Signals penetrate the polar layered deposits, probably imaging the base of the deposits. Data from the northern lowlands of Chryse Planitia have revealed a shallowly buried quasi-circular structure about 250 kilometers in diameter that is interpreted to be an impact basin. In addition, a planar reflector associated with the basin structure may indicate the presence of a low-loss deposit that is more than 1 kilometer thick.

Journal ArticleDOI
Bernard Aubert1, R. Barate1, D. Boutigny1, F. Couderc1  +601 moreInstitutions (76)
TL;DR: In this article, the decay of B{bar B} events collected at the BaBar detector at the PEP-II e{sup +}e{sup -} asymmetric energy storage ring was studied.
Abstract: The authors study the decay B{sup -} {yields} J/{psi}K{sup -}{pi}{sup +}{pi}{sup -} using 117 million B{bar B} events collected at the {Upsilon}(4S) resonance with the BaBar detector at the PEP-II e{sup +}e{sup -} asymmetric-energy storage ring. They measure the branching fractions {Beta}(B{sup -} {yields} J/{psi}K{sup -} {pi}{sup +}{pi}{sup -}) = (116 {+-} 7(stat.) {+-} 9(syst.)) x 10{sup -5} and {Beta}(B{sup -} {yields} X(3872)K{sup -}) x {Beta}(X(3872) {yields} J/{psi}{pi}{sup +}{pi}{sup -}) = (1.28 {+-} 0.41) x 10{sup -5} and find the mass of the X(3872) to be 3873.4 {+-} 1.4MeV/c{sup 2}. They search for the h{sub c} narrow state in the decay B{sup -} {yields} h{sub c} K{sup -}, h{sub c} {yields} J/{psi}{pi}{sup +}{pi}{sup -} and for the decay B{sup -} {yields} J/{psi}D{sup 0}{pi}{sup -}, with D{sup 0} {yields} K{sup -}{pi}{sup +}. They set the 90% C.L. limits {Beta}(B{sup -} {yields} h{sub c}K{sup -}) x {Beta}(h{sub c} {yields} J/{psi}{pi}{sup +}{pi}{sup -}) < 3.4 x 10{sup -6} and {Beta}(B{sup -} {yields} J/{psi}D{sup 0}{pi}{sup -}) < 5.2 x 10{sup -5}.

Journal ArticleDOI
TL;DR: Orally administered VSL#3 prevents autoimmune diabetes and induces immunomodulation by a reduction in insulitis severity, providing a sound rationale for future clinical trials of the primary prevention of type 1 diabetes by oral V SL#3 administration.
Abstract: Aims/hypothesis Recent observations suggest the involvement of the gastrointestinal tract in the pathogenesis of islet autoimmunity. Thus, the modulation of gut-associated lymphoid tissue may represent a means to affect the natural history of the disease. Oral administration of probiotic bacteria can modulate local and systemic immune responses; consequently, we investigated the effects of oral administration of the probiotic compound VSL#3 on the occurrence of diabetes in non-obese diabetic (NOD) mice.

Journal ArticleDOI
TL;DR: A randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery was conducted by as mentioned in this paper.
Abstract: Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery.

Journal ArticleDOI
TL;DR: In this paper, the main results presented in literature are summarized, focusing on the processing behaviour and final properties of natural fibres with polymeric matrices (thermoplastics, thermosets and biodegradables).
Abstract: Natural abundance, much higher strength per unit weight than most inorganic fillers, lower density and their biodegradable nature make natural fillers attractive as reinforcements of engineering polymer systems. However, certain drawbacks such as incompatibility with the hydrophobic polymer matrix, the tendency to form aggregates during processing and poor resistance to moisture greatly reduce the potential of natural fibres to be used as reinforcements in polymers. In this review, the main results presented in literature are summarized, focusing on the processing behaviour and final properties of natural fibres with polymeric matrices (thermoplastics, thermosets and biodegradables) and paying attention to the use of physical and chemical treatments for the improvement of fibre-matrix interaction and composite mechanicaln properties. This work mainly focuses on the use of natural fibres for automotive applications.

Journal ArticleDOI
TL;DR: The newer developments on the biochemistry and physiology of this group of bacteria are considered, with particular emphasis on carbohydrate and nitrogen metabolism, responses to environmental stresses, production of anti-microbial compounds and nutritional implications.
Abstract: Lactic acid bacteria (LAB) are the dominant microorganisms in sourdoughs, and the rheology, flavour and nutritional properties of sourdough-based baked products greatly rely on the activity of LAB. The newer developments on the biochemistry and physiology of this group of bacteria are considered here, with particular emphasis on carbohydrate and nitrogen metabolism, responses to environmental stresses, production of anti-microbial compounds and nutritional implications.

Journal ArticleDOI
TL;DR: White-coat hypertension was not associated with a definitely increased risk of stroke during the total follow-up period, however, WCH might not be a benign condition for stroke in the long term.
Abstract: White-coat hypertension (WCH) has been associated with a low risk for stroke, but long-term data are scanty. We analyzed individual data from 4 prospective cohort studies from the United States, Italy, and Japan that used comparable methodology for 24-hour noninvasive ambulatory blood pressure monitoring (ABPM). Overall, 4406 subjects with essential hypertension and 1549 healthy normotensive controls who were untreated at the time of initial ABPM were followed for a median of 5.4 years up to censoring or occurrence of a first stroke. At entry, mean age of subjects was 56 years (range 18 to 97). Prevalence of WCH was 9%. During follow-up, there were 213 new cases of stroke. Stroke rate (×100 person years) was 0.35 in the normotensive group, 0.59 in the WCH group, and 0.65 in the group with ambulatory hypertension. In a multivariate analysis, the adjusted hazard ratio for stroke was 1.15 (95% confidence interval [CI], 0.61 to 2.16) in the WCH group ( P =0.66) and 2.01 (95% CI, 1.31 to 3.08) in the ambulatory hypertension group ( P =0.001) compared with the normotensive group. After the sixth year of follow-up, the incidence of stroke tended to increase in the WCH group, and the corresponding hazard curve crossed that of the ambulatory hypertension group by the ninth year of follow-up. In conclusion, WCH was not associated with a definitely increased risk of stroke during the total follow-up period. However, WCH might not be a benign condition for stroke in the long term.

Journal ArticleDOI
TL;DR: No difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo, and the dose of enoxAParin used in this study proved to be safe.
Abstract: Purpose The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. Patients and Methods In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. Results Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 pat...

Journal ArticleDOI
TL;DR: In this article, a study on the reinforcement of existing wood elements under bending loads through the use of FRP materials is presented, in which an experimental program based on a four-point bending test configuration is proposed to characterize the stiffness, ductility and strength response of this article-reinforced wood beams.
Abstract: This paper presents a study on the reinforcement of existing wood elements under bending loads through the use of FRP materials. An analytical investigation was first conducted on the behavior of a generic FRP-reinforced wood section. This study, in turn, led to a numerical procedure based on non-linear wood properties, suitable for application in the design of FRP reinforcement of old, pre-existing wood beams under varying configurations of intervention layouts and materials. An experimental programme based on a four-point bending test configuration is proposed to characterize the stiffness, ductility and strength response of FRP-wood beams. Mechanical tests on the reinforced wood showed that external bonding of FRP materials may produce increases in flexural stiffness and capacity. The FRP composite material was made of High Tensile Carbon monodirectional reinforcing fabrics embedded in an epoxy resin matrix. This reinforcing method can be applied without necessitating the removal of the overhanging part of the pre-existing wood structure, thus maintaining the original historical structure. In addition, a beam non-linear model was proposed to predict ultimate load. At the end of this paper results of the experimental programme are presented and used for comparison with the numerical procedure.

Journal ArticleDOI
TL;DR: It is proposed that the water responsible for plasticizing the polymer was non-freezable (bound) water and the small fraction of such water which was absorbed at high relative humidity caused polymer degradation in the same manner as bulk water.

Journal ArticleDOI
TL;DR: It is demonstrated that NPM regulates DNA integrity and, through Arf, inhibits cell proliferation and are consistent with a putative tumor-suppressive function of NPM.
Abstract: Nucleophosmin (NPM) is a nucleolar phosphoprotein that binds the tumor suppressors p53 and p19Arf and is thought to be indispensable for ribogenesis, cell proliferation, and survival after DNA damage. The NPM gene is the most frequent target of genetic alterations in leukemias and lymphomas, though its role in tumorigenesis is unknown. We report here the first characterization of a mouse NPM knockout strain. Lack of NPM expression results in accumulation of DNA damage, activation of p53, widespread apoptosis, and mid-stage embryonic lethality. Fibroblasts explanted from null embryos fail to grow and rapidly acquire a senescent phenotype. Transfer of the NPM mutation into a p53-null background rescued apoptosis in vivo and fibroblast proliferation in vitro. Cells null for both p53 and NPM grow faster than control cells and are more susceptible to transformation by activated oncogenes, such as mutated Ras or overexpressed Myc. In the absence of NPM, Arf protein is excluded from nucleoli and is markedly less stable. Our data demonstrate that NPM regulates DNA integrity and, through Arf, inhibits cell proliferation and are consistent with a putative tumor-suppressive function of NPM.

Journal ArticleDOI
TL;DR: The sequencing of entire human mitochondrial DNAs belonging to haplogroup U reveals that this clade arose shortly after the "out of Africa" exit and rapidly radiated into numerous regionally distinct subclades, and reveals a direct maternal link between those European hunter-gatherer populations and the Berbers.
Abstract: The sequencing of entire human mitochondrial DNAs belonging to haplogroup U reveals that this clade arose shortly after the “out of Africa” exit and rapidly radiated into numerous regionally distinct subclades. Intriguingly, the Saami of Scandinavia and the Berbers of North Africa were found to share an extremely young branch, aged merely ∼9,000 years. This unexpected finding not only confirms that the Franco-Cantabrian refuge area of southwestern Europe was the source of late-glacial expansions of hunter-gatherers that repopulated northern Europe after the Last Glacial Maximum but also reveals a direct maternal link between those European hunter-gatherer populations and the Berbers.

Journal ArticleDOI
01 Mar 2005-Blood
TL;DR: In this article, the importance of platelet adhesion molecule expression on pulmonary eosinophil and lymphocyte recruitment and on leukocyte CD11b and very late antigen (VLA)-4 expression in mice was investigated.

Journal ArticleDOI
TL;DR: Energy expenditure >10 METs per hour per week obtained through aerobic leisure time physical activity is sufficient to achieve health and financial advantages, but full benefits are achieved with energy expenditure >20 METs .
Abstract: Objective To establish the impact of different amounts of increased energy expenditure on type 2 diabetes care. Research design and methods Post hoc analysis of long-term effects of different amounts of increased energy expenditure (metabolic equivalents [METS] per hour per week) through voluntary aerobic physical activity was performed in 179 type 2 diabetic subjects (age 62 +/- 1 years [mean +/- SE]) randomized to a physical activity counseling intervention. Subjects were followed for 2 years and divided into six groups based on their increments in METs per hour per week: group 0 (no activity, n = 28), group 1-10 (6.8 +/- 0.3, n = 27), group 11-20 (17.1 +/- 0.4, n = 31), group 21-30 (27.0 +/- 0.5, n = 27), group 31-40 (37.5 +/- 0.5, n = 32), and group >40 (58.3 +/- 1.8, n = 34). Results At baseline, the six groups did not differ for energy expenditure, age, sex, diabetes duration, and all parameters measured. After 2 years, in group 0 and in group 1-10, no parameter changed; in groups 11-20, 21-30, 31-40, and >40, HbA(1c), blood pressure, total serum cholesterol, triglycerides, and estimated percent of 10-year coronary heart disease risk improved (P 40, body weight, waist circumference, heart rate, fasting plasma glucose, serum LDL and HDL cholesterol also improved (P 40 (USD -579, P = 0.001). Conclusions Energy expenditure >10 METs . h(-1) . week(-1) obtained through aerobic leisure time physical activity is sufficient to achieve health and financial advantages, but full benefits are achieved with energy expenditure >20 METs . h(-1) . week(-1).

Journal ArticleDOI
TL;DR: It is shown that the bit-error rate for an uncoded OFDM system with quadrature amplitude modulation (QAM) can be expressed by the sum of a few integrals, whose number depends on the constellation size.
Abstract: We introduce an analytical approach to evaluate the error probability of orthogonal frequency-division-multiplexing (OFDM) systems subject to carrier frequency offset (CFO) in frequency-selective channels, characterized by Rayleigh or Rician fading. By properly exploiting the Gaussian approximation of the intercarrier interference (ICI), we show that the bit-error rate (BER) for an uncoded OFDM system with quadrature amplitude modulation (QAM) can be expressed by the sum of a few integrals, whose number depends on the constellation size. Each integral can be evaluated numerically, or, in Rayleigh fading, by using a series expansion that involves generalized hypergeometric functions. Simulation results illustrate that the theoretical analysis is quite accurate, especially for Rayleigh channels, and also with nonlinear amplifiers.