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Biomedical subjects

Giovanni Biasi

Publications and source records attributed to Giovanni Biasi.

6 recordsLinked to original sources
PubMed2005

A large number of T lymphocytes recognize Moloney-murine leukemia virus-induced antigens, but a few mediate long-lasting tumor immunosurveillance.

The CD8(+) T cell response to Moloney-murine leukemia virus (M-MuLV)-induced Ags is almost entirely dominated by the exclusive expansion of lymphocytes that use preferential TCRVbeta chain rearrangements. In mice lacking T cells expressing these TCRVbeta, we demonstrate that alternative TCRVbeta can substitute for the lack of the dominant TCRVbeta in the H-2-restricted M-MuLV Ag recognition. We show that, at least for the H-2(b)-restricted response, the shift of TCR usage is not related to a variation of the immunodominant M-MuLV epitope recognition. After virus immunization, all the potentially M-MuLV-reactive lymphocytes are primed, but only the deletion of dominant Vbeta rescues the alternative Vbeta response. The mechanism of clonal T cell "immunodomination" that guides the preferential Vbeta expansion is likely the result of a proliferative advantage of T cells expressing dominant Vbeta, due to differences in TCR affinity and/or cosignal requirements. In this regard, a CD8 involvement is strictly required for the virus-specific cytotoxic activity of CTL expressing alternative, but not dominant, Vbeta gene rearrangements. The ability of T cells expressing alternative TCRVbeta rearrangements to mediate tumor protection was evaluated by a challenge with M-MuLV tumor cells. Although T cells expressing alternative Vbeta chains were activated and expanded, they were not able to control tumor growth in a long-lasting manner due to their incapacity of conversion and accumulation in the T central memory pool.

Animals↗
PubMed2004

The clinical impact of interferon beta antibodies in relapsing-remitting MS.

We analysed the kinetics and clinical impact of binding antibodies (BAbs) and neutralizing antibodies (NAbs) to three interferon beta (IFNbeta) products in patients with relapsing-remitting MS (RRMS). Patients with RRMS received IFNbeta-1b 8 MIU subcutaneously (SC) every other day, intramuscular (IM) IFNbeta-1a 30 mcg once weekly, or SC IFNbeta-1a 22 mcg three times weekly for up to 4 years. The changes of BAbs and IFNbeta were measured using enzyme-linked immunosorbent assay (ELISA), and positive BAb samples were then analysed for neutralizing activity using an antiviral cytopathic effect assay. Patients were considered BAb+ if they had a positive sample with an optical density (OD)>mean + 3SD of the OD of the control sample; high BAb titers were defined as >1:500. Patients were considered NAb+ if they had titers > or =20 LU/mL, with high NAb titers defined as >1:100. The impact of BAbs and NAbs on relapses and Expanded Disability Status Scale (EDSS) score also was evaluated. Thirty patients were enrolled in each treatment group. Over the course of the study, 83% of patients developed BAbs to IFNbeta-1b, 13% to IM IFNbeta-1a, and 47 % to SC IFNbeta-1a. Forty percent of patients developed NAbs to IFNbeta-1b, 6.7% to IM IFNbeta-1a, and 26.7% to SC IFNbeta-1a. Of 22 NAb+ patients, 10 patients (45.5%) demonstrated high titers of both NAbs and BAbs (20% IFNbeta-1b, 3.3% IM IFNbeta-1a, 10% SC IFNbeta-1a). The relapse rate significantly increased after the appearance of high NAb titers (p=0.03); however, an even higher significance level (p<0.001) was observed in patients with high titers of both NAbs and BAbs. In 10 patients with high titers of both NAbs and BAbs, an increase in mean EDSS score from 2.2 +/- 0.8 at baseline to 3.6 +/- 1.2 at year 2 (p<0.01) was observed. NAb-negative patients showed no significant change in EDSS score at year 2. These findings demonstrate that high titers of both BAbs and NAbs reduce the clinical efficacy of IFNbeta in patients with RRMS, which is important for the long-term efficacy of these drugs.

Adolescent↗
PubMed2004

The MBP-reactive repertoire is shaped by recognition of minor histocompatibility antigens.

While it is known that the degeneracy of T-cell antigen recognition is involved in many aspects of T cell-immunology, its importance in the selection of the T cell repertoire remains an aspect to be better investigated. Here we examined if an intrathymic degenerate T cell recognition mechanism shapes the myelin basic protein (MBP)-reactive repertoire inducing resistance to experimental autoimmune encephalomyelitis (EAE) in some MHC and/or minor histocompatibility antigens (MiHAs) heterozygous F1 mice bearing the H-2(s) susceptibility allele. We found a considerable degree of cross-reactivity between MBP and MiHAs encoded in various EAE resistant mouse strains: (1) MBP-specific T cells can be re-stimulated in vitro by cells expressing these MiHAs and maintain their encephalitogenic activity, and (2) lymphoid cells from parental strains that generate EAE resistant F1 hybrids can induce disease relapse when injected into EAE-susceptible hosts. The results suggest that heterozygosity, through the degeneracy of T cell antigen recognition mechanism, may provide further means to constrain the potential autoreactive repertoire.

Animals↗
PubMed2003

Linear scleroderma associated with progressive brain atrophy.

Linear scleroderma (LS) is characterized by scleroatrophic lesions affecting limbs and legs, unilaterally. Neurological involvement may be associated with ipsilateral facial and skull involvement in disorders referred to clinically as LS 'en coup de sabre', and Parry-Romberg syndrome. We report a child with LS presenting with a severe neurological disorder characterized by epilepsy, progressive mental deterioration and a rapid process of atrophy involving the ipsilateral cerebral hemisphere, but not associated with an overlying facial structure involvement. Functional brain studies showed a reduction in the diameter of the left internal carotid and of the left middle cerebral artery. Our observations suggest that neuroimaging studies should be considered in all patients with linear scleroderma, and such studies become necessary when neurological symptoms occur.

Brain Diseases↗
PubMed2002

Reactivity to superficial and deep stimuli in patients with chronic musculoskeletal pain.

In this study, we evaluated pain sensitivity in patients with fibromyalgia or other types of chronic, diffuse musculoskeletal pain to establish whether fibromyalgia represents the end of a continuum of dysfunction in the nociceptive system. One hundred and forty five patients and 22 healthy subjects (HS) completed an epidemiological questionnaire to provide information about fatigue, stiffness, sleep, the intensity of pain (VAS 0-100) and its extent both at onset and at present. Algometry was performed at all American College of Rheumatology (ACR) tender points and at ten control points. Patients were divided into five main groups: fibromyalgia (FS) patients, secondary-concomitant fibromyalgia (SCFS) patients, patients with widespread pain (WP) but not reaching the ACR criterion of 11 tender points, patients with diffuse multiregional pain (MP) not reaching the ACR criteria (widespread pain, tender point counts), and patients with multiregional pain associated with at least 11 tender points (MPTE). von Frey monofilaments were used to assess superficial punctate pressure pain thresholds. Heat and cold pain thresholds were determined with a thermal stimulator. Ischemic pain was assessed by the cold pressure test and the submaximal effort tourniquet test. The scores for stiffness and present pain intensity gradually increased concomitantly with the increase in tender point count and pain extent. The pressure pain thresholds for positive tender and positive control points were significantly lower in the SCFS, FS and MPTE groups than in HS, MP and WP groups, the latter three groups displaying similar values. In all groups, there were no differences in pain thresholds between positive tender and positive control points. The heat pain threshold and the pain threshold in the cold pressure test were lower in the FS and SCFS groups than in HS. The cold pressure tolerance was lower in patients with widespread pain than in HS. In the von Frey test, all patient groups except MP had similar values, which were significantly lower than in HS. Finally, all patient groups displayed lower tourniquet tolerance than HS. In each psychophysical test, patients with widespread pain and patients with multiregional pain showed similar thresholds; however, the thresholds in the MP or MPTE groups differed from those in the FS and SCFS groups. In the FS group, pain thresholds and pain tolerance did not differ according to the presence of ongoing pain at the stimulated site and were not correlated to ongoing pain. The results indicate that dysfunction in the nociceptive system is already present in patients with multiregional pain with a low tender point count; it becomes more and more severe as the positive tender point count and pain extent increase and it is maximal in fibromyalgia patients.

Adult↗