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Biomedical subjects

G Tonietti

Publications and source records attributed to G Tonietti.

At least 37 records · Page 2Linked to original sources

Soluble CD8 antigen in systemic sclerosis.

In 15 patients suffering from systemic sclerosis (PSS) the function of CD8+ circulating lymphocytes was assayed by determining soluble CD8 antigen (sCD8) both in sera and in 48 hr PHA-conditioned media of peripheral blood mononuclear cells (PBMCs). Furthermore, the frequency of circulating activated CD8+ cells, which express DR antigens, interleukin-2 receptor, and transferrin-receptor, was determined by cytofluorographic analysis. The results of this preliminary study indicate that only in 6 PSS sera sCD8 was elevated as compared to healthy controls; furthermore, we found slightly increased sCD8 in culture media from PSS patients. The frequency of circulating activated CD8+ cells was similar both in PSS patients and in controls. Overall, our findings suggest that CD8+ cell activation is not a major phenomenon in PSS.

Adult↗

[Cyclosporin (CyA) and H2 antagonists].

An experimental study on rats in order to discovery any possible interaction between Ciclosporin (CyA) and H2-receptor antagonists has been carried out. The results obtained demonstrated that the serum levels of CyA were higher in rats treated with CyA and Cimetidine or Ranitidine, but not Famotidine. It is probable that the increase of ciclosporinaemia is the consequence of an increased hepatotoxicity due to administration of Cya in association with Cimetidine or Ranitidine.

Animals↗

Drug interaction between cyclosporin A and nizatidine in Sprague-Dawley rats.

The H2-receptor antagonists seem to be effective in prevention and treatment of stress ulcer in transplant recipients. In a previous study on rats, an increase was observed in cyclosporinaemia and hepatotoxicity after administration of cimetidine or ranitidine in association with cyclosporin A (CyA). On the contrary, famotidine does not influence the blood CyA levels. The aim of the study was to detect the possible synergistic nephro- and hepatotoxicity of nizatidine administered in association with CyA, assaying the serum creatinine, the ALT and AST levels, and histological features of thirty young male Sprague-Dawley rats, divided into 6 groups of five animals each. After 10 days, all the rats were sacrificed, their blood was collected to assay serum creatinine, ALT, AST and serum CyA levels: kidneys and livers were processed for light microscopy. The results obtained demonstrated that, while the level of creatinine was normal in each group, the average level of transaminase and the serum levels of CyA were significantly higher in the animals receiving the association of CyA and nizatidine. Furthermore, this group demonstrated a mild infiltrate of the liver characterized in some cases with eosinophilic polymorphonuclear cells. In light of the results obtained, it is probable that the increase of cyclosporinaemia is the consequence of an enhanced hepatotoxicity due to administration of CyA in association with nizatidine.

Animals↗

Polyclonal B lymphocyte activation in progressive systemic sclerosis.

In 13 women affected by progressive systemic sclerosis (PSS) the activation state of circulating B lymphocytes by use of monoclonal antibodies and the in vitro IgG, IgA, IgM synthesis by peripheral blood mononuclear cells (PBMC) cultured with or without pokeweed-mitogen (PWM) were evaluated. The total and "activated" B lymphocytes were increased. The supernatants of PBMC cultured without PWM contained increased IgG and IgA levels; only in two patients, however, were IgM levels increased. The addition of PWM augmented IgG and IgA levels only in three cases and never IgM levels. Our results indicate that the polyclonal hyperactivity of B lymphocytes is a major immunologic feature in PSS patients. The lack of increase of in vitro immunoglobulin synthesis in the presence of PWM suggests either that B lymphocytes, already maximally activated in vivo, are unresponsive to further mitogen stimulation or that a more complex imbalance of B lymphocyte responsiveness to PWM may exist.

Adult↗

Immunofluorescence study of thymuses of mice given Friend leukemia virus: conventional vs monoclonal antibodies.

In the course of a study of the early effects of Friend Leukemia Virus (FLV) infection in thymus structure and function, evidence of early localization of infectious FLV in the thymic type I and type II epithelio-reticular cells of susceptible mice was obtained. Such evidence was based upon bio-assay, ultrastructural and immunofluorescence observations. As for the latter, conventional monospecific sera against FLV p30 and gp70 antigens as well as two distinct monoclonal antibodies recognizing FLV gp70 epitopes were employed. Both monoclonal antibodies stained with a granular pattern the cytoplasm of type I and II epithelio-reticular cells from susceptible mice injected with live FLV. On the contrary, conventional monospecific sera diffusely stained the cytoplasm of all epithelio-reticular cells of the thymus, independently of mice inoculation with and susceptibility to virus, possibly recognizing tissue-associated normal mouse antigens and/or cross-reacting antigens of other ecotropic viruses.

Animals↗

T cell differentiation antigens expressed by peripheral blood lymphocytes in Crohn's disease.

The aim of the present study was to investigate whether an imbalance of peripheral blood immunoregulatory T cells is a feature of Crohn's disease. The cluster of differentiation antigens 3,4 and 8 were investigated and the relative prevalence of PBL expressing each antigen was defined using a panel of three monoclonal antibodies (OKT3, OTK4 and OKT8). A significant decrease in the OKT3 and OKT4 positive cells was found in CD patients as compared with healthy controls. No significant difference was observed between patients and controls in the proportion of T8 positive cells and in the T4/T8 ratio. While confirming a significant decrease of circulating total resting T cells in patient with CD, the results of this study indicate that the disease is not primarily related to an imbalance of the proportion of the T cells subsets.

Adult↗

Effects of in vivo Friend leukemia virus infection on levels of serum thymic factors and on selected T-cell functions in mice.

The levels of serum thymic factor(s) (STF), of Thy-1.2 positivity of splenocytes [as measured by their azathioprine (AZ) sensitivity], and of Thy-1.2-positive "spontaneous" spleen rosette-forming cells (SSRFCs), as well as the presence of infectious virus in the thymus, were assessed as a function of time after virus inoculation in susceptible DBA/2, partially resistant BALB/c, and fully resistant C57BL/6 mice given the polycythemia- or anemia-inducing strain of Friend leukemia virus (FLV-P and FLV-A, respectively). As early as Days 2 to 3, the levels of STF and of AZ sensitivity of splenocytes were profoundly decreased in DBA/2 mice, and, to a lesser extent, in BALB/c mice given FLV-P; however, SSRFCs/spleen were increased in both mouse strains. Conclusive evidence of infectious FLV-P was obtained in the thymuses of DBA/2 mice soon after infection. In mice of the same strains infected with FLV-A, STF levels were similarly decreased, but AZ sensitivity of splenocytes was unaffected, and SSRFCs were decreased. Evidence of early FLV-A infection in the thymus of DBA/2 mice was likewise obtained. In C57BL/6 mice given FLV-A, STF levels, AZ sensitivity of splenocytes, and SSRFC showed changes similar to, but of lower magnitude than, those in BALB/c mice. On the other hand, in C57BL/6 mice given FLV-P, the decrease in STF and AZ sensitivity was almost as pronounced as in susceptible DBA/2 mice in the face of complete absence of infectious virus or viral markers in the thymuses. The observed changes are ascribed to virus infection in view of the following: (a) good temporal correlation between these changes and virus infection; (b) absence of any change in mice given heat-inactivated viruses or spleen homogenate of normal DBA/2 mouse spleen; (c) overall good correlation between mouse genotype and genetic (Fv-1 and Fv-2) restrictions of virus infection on one hand and the magnitude of the observed changes on the other. In particular, the decrease in STF and SSRFC levels is ascribed to the replication-competent (Friend-murine leukemia virus) component of Friend leukemia virus complex, whereas the decrease in AZ sensitivity of splenocytes and the increase of SSRFCs are ascribed to the defective spleen focus-forming virus component of the complex. All changes described so far were transient, since they were not detectable beyond 42 days after virus inoculation in overtly leukemic animals. The observed derangements of thymus-derived immune functions may play an important cofactor role during the onset of leukemia in mice genetically permissive to Friend leukemia virus replication and transformation, but they do not seem relevant to the maintenance of leukemia.

Animals↗

HNK-1 monoclonal antibody (Leu-7) in the identification of abnormal expansions of large granular lymphocytes.

Among 12 cases of chronic T lymphoproliferative disorders we observed, six patients showed an expansion of mononuclear cells with azurophilic granules usually referred to as large granular lymphocytes or LGL. Cells obtained from five patients with these abnormal LGL proliferations were studied with several surface markers including their reactivity with the HNK-1 monoclonal antibody reported to be specific for LGL. Cells in four out of five cases were HNK-1 positive. Whereas normal LGL have been reported to be unreactive with several T cell markers, three cases showed the co-existence of HNK-1 and surface markers expressed by T cells. Two cases were characterized by the proliferation of OKT8 cells. Cells from one patient were HNK-1 positive but did not express T or monocytic antigens. These cells were apparently not completely mature since alpha-naphthyl acetate acid esterase activity was negative. Cells from the remaining case were HNK-1 negative and positive for T and monocytic antigens. An increase of OKT-10 cells was observed in only one patient. Our data indicate that proliferations of LGL represent a remarkable proportion of the rare cases of sheep erythrocyte rosetting chronic lymphocytic leukaemias or lymphomas. Besides the morphology of LGL, the rosetting ability and the negativity for peroxidase, cells from these cases showed a vast heterogeneity of other structural and functional markers, possibly reflecting different stages in the maturation of these cells. The HNK-1 monoclonal antibody proved to be an important marker in the identification of these cases.

Adult↗

[The immunity of senescence. Study of lymphocytes in vitro. I: Rosette forming lymphocytes].

E and EAC rosettes forming lymphocytes were evaluated in 25 elderly subjects (mean age 84.76 years) without manifestations of neoplastic or infectious diseases. The percentage of E rosettes appeared within the normal range in about 50 per cent of cases and below normal in remaining 50 per cent. No evident sex-related differences were observed. The percentage of EAC rosettes showed a larger distribution of values. In fact, 56 per cent of cases fell within normal limits, 26 per cent was higher and 20 per cent lower than normal. Our results are in agreement with the data reported in the most recent literature, which indicates that the main target of immune system senescence is the T-cell population, while B cells do not show significant age-related variations. The significant number of cases with percentages of EAC rosettes higher than normal may be attributed to the failure of immune homeostatic mechanisms normally exerted by T cell subpopulations. Further studies on several immune system functions in advanced age are in progress.

Aged↗

[Immunological implications in the pathogenesis of Horton arteritis].

Fragments of temporal artery obtained by surgical biopsy from 3 patients suffering from Horton arteritis were employed for immunopathologic studies by direct immunofluorescence. In 2 of the cases, granular deposition of IgM, C1q and C3 but not of albumin were observed in the wall of vasa vasorum of the temporal artery. Elution techniques determined the disappearance of the immunoreactants. In one case in which biopsy fragments of temporal artery were obtained prior to and after steroid treatment it was observed that IgM and complement, previously present, disappeared after such treatment. The data reported indicate that indeed immunologic factors play a role in the pathogenesis of the disease and that the immunoreagents present on the wall of vasa vasorum are not evidence of increased vascular permeability but indicate an active immunologic process which takes place in them.

Albumins↗

[Incidence, type and significance of anti-myocardial autoantibodies in patients undergoing cardiac surgery].

The incidence of anti-myocardial autoantibodies was investigated in 62 patients suffering from congenital or acquired cardiopathy prior to and 1, 10 and 20 days after cardiac surgery. Anti-myocardial autoantibodies were present in about 23.7 per cent of patients even before surgery, practically doubled one day after intervention, reached their peak (60-70 per cent) at 10 days from surgery and began to diminish at 20 days. At all times and incidence was higher in patients with acquired cardiopathy than in those with congenital heart diseases. In the large majority of cases, the autoantibodies were of the IgG class, of the striational type and in low titers. The relevance of anti-myocardial autoantibodies in the pathogenesis of cardiac lesions and the possible causes of the reversibility of the autoimmune phenomenon are discussed.

Autoantibodies↗

Immuno-electronmicroscopic study of human EA rosettes.

The immuno-electronmicroscopic study of human EA rosettes, using ferritin-labelled anti-human IgG antiserum, showed clusters of ferritin granules at the points of contact between erythrocytes and lymphoid cells, indicating that the links between Fc fragment of IgG on the surface of erythrocytes and specific receptor on the surface of lymphoid cell correspond to the sites of morphological interaction between the 2 cell types.

Erythrocytes↗

Ultrastructure of cell-mediated immunity. I. Comparison between E and EA rosettes.

The ultrastructural comparison between E and EA rosettes showed that, in the former, the rosetting lymphocytes are mostly round in shape and their interaction with sheep erythrocytes only consists of limited areas of membrane contact, in the latter, rosetting lymphocytes are mostly in the shape of uropods and surrounding ox red cells show pseudopods protruding towards the lymphocyte and coming into contact with it.

Animals↗