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Biomedical subjects

P L Meroni

Publications and source records attributed to P L Meroni.

At least 145 records · Page 8Linked to original sources

Increased rate of survival in Streptococcus pneumoniae-infected rats treated with the new immunomodulator Pidotimod.

Wistar rats infected with Streptococcus pneumoniae (type III ATCC) rapidly develop an acute form of experimental lobar pneumonia (ELP) with death of 80-90% of the animals by 6 days after the infection. Prophylactic treatment of these animals with the novel immunomodulator Pidotimod, at the dose of 25 mg/kg bw, significantly increased their rate of survival as compared to the control group (50 vs. 90% respectively). Recovery from the infection appeared definitive since all the Pidotimod-treated survivors were alive and in good condition at the end of the observation period (45 days post infection). Prophylactic treatment with higher or lower doses of the drug was ineffective. Therapy with Pidotimod was not effective. This preliminary study suggests that Pidotimod may have contributed to activation of specific and non-specific immune effectors involved in the host response to S. pneumoniae infection.

Adjuvants, Immunologic↗

Markers of vascular injury in Behçet's disease associated with retinal vasculitis.

The pathogenesis of vascular damage in Behçet's disease (BD) is still unknown. We investigated anticardiolipin antibodies (AC) in a genetically homogeneous group of Italian patients with BD and retinal vasculitis. In a subset, we examined the level of factor VIII-related antigen and antiendothelial cell antibodies (AECA). We found a high prevalence of AC; AECA were not found in most of our patients. Only three patients had raised levels of factor VIII-related antigen, all of whom had systemic involvement. We believe BD may be considered as a vasculitis of unknown origin in which several and different pathogenetic factors may play a role.

Adolescent↗

Histopathological findings in a case of systemic lupus erythematosus-associated anti-phospholipid syndrome.

The vessel anatomopathological lesions in a patient with systemic lupus erythematosus associated anti-phospholipid syndrome are described. Vasculitic lesions were nearly absent but small vessels showed hyalin thrombosis or substenosis due to subendothelial deposition of amorphous PAS-positive material in different anatomical districts. These findings can be related to the patient's clinical manifestations, particularly the central nervous system involvement and can be discussed regarding the possible pathogenetic mechanisms.

Adult↗

FK-506 prevents diabetes in diabetes-prone BB/Wor rats.

The effect of the immunosuppressant FK-506 on the development of diabetes in BB/Wor rats was investigated. Using a treatment schedule (25 micrograms i.m. from day 27 to 120), not associated with detectable general ill effects, this drug was found to completely inhibit the appearance hyperglycemia and to reduce the histological signs of pancreatic insulitis. The treatment was also able to reduce the percentages of Ia+ T-lymphocytes and to block the appearance of detectable serum levels of gamma interferon (IFN).

Animals↗

Enhanced percentage of Leu M3+DR+ and Leu M3+CD25+ cells in newly diagnosed IDDM patients.

The percentage of Leu M3+DR+ and of Leu M3+CD25+ cells was determined by means of immunofluorescence analysis in a group of patients with insulin dependent diabetes mellitus (IDDM). Our results show that an increased percentage of these cells may occur in the early stage of the disease. These data provide evidence for a "phenotypical" activation of Leu M3+ cells at the onset of the disease and warrant future studies to evaluate the potential role of these cells in the pathogenesis of IDDM.

Adolescent↗

Correlation between islet cell antibodies and anti-cytomegalovirus IgM and IgG antibodies in healthy first-degree relatives of type 1 (insulin-dependent) diabetic patients.

To investigate whether cytomegalovirus (CMV) infection may be related to islet cell antibodies (ICA) production and/or to insulin-dependent diabetes mellitus (IDDM) development, we have analyzed the prevalence of anti-CMV, IgM, and IgG antibodies and of ICA in 80 healthy siblings of IDDM patients (HSIDDP) and in 60 control subjects with negative familiar anamnesis of IDDM. HSIDDP and controls were also typed for HLA-A-B-C and DR antigens. IgM and IgG anti-CMV were detected by an ELISA method, whereas the ICA assay was performed by standard indirect immunofluorescence on 5-microns unfixed sections of human pancreas. HLA-A-B and C antigens were studied by standard microlymphocytotoxicity; DR antigens were also studied by a standard microlymphocytotoxicity on a B-enriched lymphocyte population. Our results indicate a significant association (P less than 0.0001) between high titers of anti-CMV IgG antibodies and ICA in HSDIDDP, whereas no correlation was found between the presence of any HLA-A-B-C and DR antigens and the prevalence of anti-CMV IgM and IgG antibodies and/or ICA. Thus, these data may support the hypothesis that a chronic CMV infection may be associated with ICA production whereas other factors seem to be needed for the complete development of type 1 diabetes.

Adolescent↗

Enhanced percentage of CD5+ B lymphocytes in newly diagnosed IDDM patients.

The percentage of CD5+ B lymphocytes, the prevalence of islet cell antibodies (ICA) and of anti-insulin autoantibodies (IAA) and HLA-A-B-C and DR antigens were studied in 32 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients, in 12 non-insulin-dependent diabetes mellitus (NIDDM) patients and in 12 healthy subjects. The percentage of CD5+ B lymphocytes ranged from 18% to 51.2% (mean 40.3 +/- 11%) in IDDM patients, whereas in NIDDM patients and in controls it ranged from 20% to 25.2%, (mean 21.3 +/- 4.1%) and from 16% to 24%, (mean 19.3 +/- 1.9%), respectively (P less than 0.01 vs. NIDDM patients and vs. controls). There was no correlation between a higher percentage of CD5+ B lymphocytes and the presence of ICA and/or IAA, and their titres, and/or of any HLA-A-B-C and DR antigens. Thus, an enhanced percentage of CD5+ B lymphocytes may be present in newly diagnosed IDDM patients; the possible role of this cell type in the pathogenesis of IDDM needs further investigation.

Adolescent↗

Anti-endothelial cell antibodies in patients with Wegener's granulomatosis and micropolyarteritis.

Anti-endothelial cell antibodies (AECA) have been detected by cell surface radioimmunoassay in nine out of 15 patients with micropolyarteritis (MPA) and in two out of five patients with Wegener's granulomatosis. AECA mostly belonged to the IgG isotype and were present in the active phase of the diseases. These antibodies were not detectable in 10 sera from patients with essential mixed cryoglobulinaemia, suggesting that they were not a mere epiphenomenon consequent to the inflammatory vascular injury. The binding activity was not related to ABH antigens or to HLA class I antigens displayed by resting human endothelial cells in culture and was not influenced by removing immune complexes. Absorption of the anti-neutrophil cytoplasmic antibodies (ANCA), present in MPA and Wegener's granulomatosis sera, did not affect the endothelial binding. AECA-positive sera did not display lytic activity against endothelial cells, neither alone nor after addition of fresh complement or normal human peripheral blood mononuclear cells. Although AECA are not cytolytic for endothelial cell monolayers in vitro, the reactivity against intact endothelial cells suggests their possible involvement in in vivo pathological processes affecting vascular structures in small vessel primary vasculitides.

Adult↗

Combination of mutant EL-4 thymoma cells and EBV-infection in B lymphocyte activation a) EBV-infection of EL-4-activated lymphocytes. b) Use of EL-4 cells as feeders for lymphoblastoid cell lines.

The combination of mutant EL-4 thymoma cells and Epstein-Barr virus (EBV)-infection in the activation of human B lymphocytes was studied with two approaches: a) limiting numbers of B cells were first activated by EL-4 contact in order to expand the B cell population and then infected with EBV. Results show that EBV could induce further Ig synthesis, although was unable to determine proliferation or to generate immortalized lines from EL-4 activated cells. b) EL-4 cells were compared to conventional PBM as feeders for cultures of established lymphoblastoid cell lines (LCL) at low cell densities. EL-4 feeder activity was strictly dependent on the presence of phorbol-myristate-acetate (PMA) and supernatant from stimulated T-lymphocytes (T-SN). EL-4 feeders induced earlier proliferation peak and greater Ig synthesis by LCL. The latter effect could be also mediated by the addition of PMA and T-SN, even if a cooperating cell-to-cell signal by PMA and T-SN-sensitized-EL-4 cells could not be excluded. Altogether results indicate that EL-4 cells do not represent a clear advantage over classic PBM as feeders for cultures of established LCL at low cell densities.

B-Lymphocytes↗

In vitro modulation of human endothelial cell growth by Kaposi's sarcoma sera.

Sera from patients affected either by the classic/Mediterranean form (5 patients) and human immune deficiency virus (HIV)-associated (12 patients) form of Kaposi's sarcoma (KS) were compared in supporting endothelial cell in-vitro proliferation. Healthy blood donors (15) and a group of 7 HIV-positive drug addicts with no dermatological involvement were used as control groups. Endothelial cell growth was assessed by means of a [3H]thymidine incorporation and by an optical density direct cell-counting assay. Our results indicate that, at the highest concentrations, sera obtained from patients affected by KS with no sign of HIV infection induced significantly higher levels of endothelial cell proliferation when compared with HIV-associated KS and with normal controls. This growth-promoting activity was apparently cell selective, being present in endothelial cell but not in fibroblast cultures.

Cell Count↗

Synergisms between different activation pathways in adult and aged human lymphocytes.

The present report investigates the synergistic effects of different agents (phytohaemoagglutinin (PHA), anti-CD3, phorbol-12-myristate-13-acetate (PMA) and Ionomycin on T cell activation. Results indicate that in normal lymphocytes PMA causes a dose-dependent decrease of PHA-induced blastogenesis and a marked enhancement of anti-CD3-induced 3H-thymidine uptake. There is positive synergism when cells are costimulated with PMA and the calcium ionophore Ionomycin. These data show that phorbol esters can exert either positive or negative synergisms depending on the experimental conditions. We also studied the simultaneous stimulation with PHA and anti-CD3 which gives an addictive effect for the minimal doses of the two stimuli, and an appreciable negative synergism for their highest concentrations. In order to evaluate T lymphocyte functions in the age-associated immune defect, PHA plus anti-CD3 and PMA plus Ionomycin costimulation assays were applied to a population of healthy elderly subjects. An additive effect is found after costimulation with the highest doses of PHA and anti-CD3, at variance with the negative synergism found in younger adult controls. Following costimulation with PMA plus Ionomycin, elderly subjects also display an impaired response, as compared to adult controls. No correlation was found with PHA-, anti-CD3- and PMA plus Ionomycin-induced T cell proliferation. These results underline the complexity of age-associated immune defects and suggest that alterations in different mechanisms of lymphocyte activation are responsible for the immune deficiency of aging.

Adult↗

Heterogeneity of immune responsiveness in healthy elderly subjects.

We studied a group of healthy elderly subjects (satisfying the SENIEUR Protocol admission criteria), chosen as a model of age-associated immune deficiency on the basis of their reduced skin reactivity to recall antigens. Results show that aged subjects, taken as a whole, display impaired T-cell functions: reduced blastogenetic responses to mitogens, IL-2 production, responsiveness to exogenous IL-2, and percentage of Tac positive blasts. However, the age-associated immune defect shows a wide range of impairment, even in a relatively homogeneous group of anergic/hypoergic subjects. In fact, a considerable proportion of our elderly subjects displays responses comparable with those of adult controls. These observations suggest that (a) immune deficiency is not a characteristic of aging per se; (b) cutaneous delayed hypersensitivity is not a criterion sensitive enough to identify people with age-associated immune deficit; and (c) more than one test is required to evaluate T-cell impairment in aging.

Aging↗

In vivo immunopotentiating activity of thymopentin in aging humans: modulation of IL-2 receptor expression.

The effect of thymopentin treatment was investigated in immunocompromised elderly subjects. Thymopentin was able to increase IL-2 production and IL-2 receptor expression, as assessed on PHA-activated blasts by percentage of Tac-positive cells and response to exogenous IL-2. After treatment, an increased precursor frequency, estimated by limiting dilution analysis, of PHA-responding lymphocytes was observed in two out of six subjects tested. In vitro experiments with thymopentin show that the drug was able to enhance blastogenesis by PHA of elderly lymphocytes but not of adult cells. These results indicate that (a) the increased IL-2 synthesis/IL-2 receptor expression may be the crucial mechanism of the immunopotentiating activity of the drug in elderly subjects and (b) an increased intrinsic T-cell responsiveness seems to be responsible for this immunopotentiating activity, although an increase in the size of the responsive T-cell pool could not be excluded.

Adjuvants, Immunologic↗

In vitro and ex vivo effect of RU41740 on human polymorphonuclear leukocyte function.

We investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae and possessing immunomodulating properties, on human neutrophil functions in vitro and ex vivo. Our in vitro results showed that RU41740 increased complement- and Fc receptor-dependent phagocytosis. Moreover, the drug enhanced the oxidative metabolism (assessed by chemiluminescence) both in resting and stimulated cells; in the latter case the RU41740-induced enhancement was observed when neutrophils were stimulated with opsonized particles of N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not when phorbol myristate acetate was used. Using otherwise effective experimental conditions, RU41740 did not affect spontaneous or FMLP-induced neutrophil migration. For the ex vivo experience we tested neutrophils of ten elderly subjects with a previously demonstrated phagocytic defect. These subjects were treated orally with RU41740 at a daily dose of 2 mg for 1 week during the first month, and of 1 mg for 1 week in the second month. In this population, RU41740 was able to restore the impaired phagocytic activity and to induce a significant increase of spontaneous chemiluminescence (CL); stimulated CL was also positively influenced. These effects on neutrophils provide new explanatory bases for the immunostimulatory activity of RU41740.

Adjuvants, Immunologic↗