Biomedical subjects

W Barcellini

Publications and source records attributed to W Barcellini.

At least 55 records · Page 3Linked to original sources

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

In vitro modulation of human monocytes functions by RU 41740 (Biostim).

The in vitro effects of RU 41740, a mixture of two glycoproteins extracted from K. pneumoniae and possessing immunomodulatory activity, on human monocyte's cytotoxic activity, migratory capacity and monokine production were investigated. Exposure to RU 41740 in nanogram concentrations was associated with rapid increases in IL-1 and TNF production and marked augmentation in the monocytes' killing of TNF-sensitive targets, whereas killing of TNF-insensitive targets required longer exposures to microgram concentrations of this drug. Using otherwise effective treatment conditions, RU 41740 did not directly affect monocyte's spontaneous and FMLP-induced migration. The possible role of mononuclear cells stimulation and increased production of effector and regulatory monokines in the immunomodulatory activity of this product is addressed.

Adjuvants, Immunologic↗

PubMed1988

Relationship between anti-cardiolipin and anti-endothelial cell antibodies in systemic lupus erythematosus.

Anti-endothelial cell antibodies (AECA) have been detected in 51 lupus sera by cell surface radioimmunoassay with a prevalence of 39.2% for IgG and 45.1% for IgM-AECA. No correlations were found between AECA and different clinical or laboratory parameters, including the presence of anti-cardiolipin antibodies and signs associated with the presence of anti-phospholipid antibodies. However, absorption with cardiolipin liposomes partially inhibited endothelial cell binding, and affinity purified anti-cardiolipin antibodies were able to react with intact human endothelial cells. The binding did not occur via Fc receptors since blocking of Fc receptors with rabbit IgG did not affect the endothelial cell reactivity. Taken together our findings support the hypothesis that antibodies directed against negatively charged phospholipids can be part of the anti-endothelial cell antibodies in certain lupus sera. The possible role of these cross-reacting antibodies in the pathogenesis of vascular thrombosis in lupus patients is discussed.

Antibodies↗

PubMed1988

Study on the interference of ticlopidine on the immune system.

In-vitro and ex-vivo studies have been performed in order to investigate the possible interference of ticlopidine on different lymphocyte parameters. In vitro, ticlopidine displays a dose-dependent inhibition of both spontaneous and lectin-induced 3H-thymidine incorporation by normal lymphocytes. Moreover the highest drug concentrations also reduce the in-vitro PWM-stimulated Ig synthesis. Lymphocyte tests performed in healthy volunteers after a 10-day oral treatment (250 mg/day) show only a slight reduction of PHA- and ConA-induced proliferative responses and in-vitro PWM-stimulated Ig synthesis. The values found after treatment however remain within the normal range, excluding a clear interference of ticlopidine on the immune parameters tested. In addition the treatment does not affect the white blood cells nor the lymphocyte subset distribution identified by the monoclonal antibodies OKT3, OKT4 and OKT8.

Cells, Cultured↗

PubMed1988

Silybin inhibition of human T-lymphocyte activation.

Silybin, a 3-oxyflavone occurring in the thistle Silybum marianum, displays a dose-dependent inhibition of in-vitro lymphocyte blastogenesis induced by lectins (phytohaemagglutinin, Concanavalin A and pokeweed) and by anti-CD3 monoclonal antibody. The drug has no effect on cell viability and spontaneous 3H-thymidine incorporation, suggesting that the inhibitory activity is not due to aspecific toxicity. Since all the T-cell responses investigated require cell-membrane-associated events, the effect of silybin is probably at the level of the cell membrane, as for other flavonoids. Addition of CuSO4 prevents the inhibitory activity of silybin on PHA-induced proliferative response, indicating that the drug could exert its activity also by virtue of a chelation mechanism.

Antibodies, Monoclonal↗

PubMed1987

In vivo immunopotentiating activity of thymopentin in aging humans: increase of IL-2 production.

The effect of thymopentin (TP-5) treatment on lymphocyte immune functions has been investigated in immunocompromised aged subjects. TP-5 was able to improve the cutaneous delayed hypersensitivity (CDH) to recall antigens and the proliferative response to phytohemagglutinin (PHA), concanavalin A, and Pokeweed (PWM) as well as the PHA-induced interleukin-2 (Il-2) production. On the other hand, no detectable changes were induced by TP-5 treatment either on PWM-induced immunoglobulin synthesis or on lymphocyte subsets identified by monoclonal antibodies. Our results suggest that the enhancement of Il-2 synthesis might be a crucial mechanism of the immunopharmacological action of TP-5 in aging humans.

Adjuvants, Immunologic↗

PubMed1987

Immunomodulating activity of RU 41740: in vitro and in vivo studies on human lymphocytes.

A group of institutionalized elderly subjects, selected on the basis of their skin hypoergy and displaying different kinds of T and B lymphocyte impairments has been chosen as a model to verify the in vivo immunopotentiating activity of RU 41740 on human lymphocytes. Oral treatment with the drug was able to: restore or improve the cutaneous delayed hypersensitivity to recall antigens; significantly increase the blastigenetic response to mitogenic and submitogenic doses of PHA and PWM and improve the in vitro PWM-induced synthesis of IgG and IgM. The immunopharmacological activity of RU 41740 appeared to persist three months after the end of therapy, without any direct stimulating activity on the peripheral blood lymphocytes. The in vitro results seem to suggest that peripheral lymphocytes are not directly influenced by the drug.

Adjuvants, Immunologic↗

PubMed1987

Experiences with immunomodulant agents in HIV infections.

Drug addicts with persistent generalized lymphadenopathy displayed the following immunological abnormalities: an inverted OKT4/OKT8 ratio, a depressed in vitro blastogenetic response to phytohemagglutinin and pokeweed mitogen (PWM), a reduced ability of PMNL to phagocytose and kill Candida albicans spores and to migrate in presence of a chemotactic factor. Thymopentin treatment (50 mg s.c. 3 times/week for 3 weeks and repeated after 3 months at 50 mg s.c. once a week for 3 months) improved OKT4+ lymphocytes (p less than 0.05) and the blastogenesis to PWM (p less than 0.01); moreover, at the end of the first cycle, the chemotaxis of neutrophils was increased to normal values.

AIDS-Related Complex↗

PubMed1987

Interleukin 2 enhancement of anti-T3-induced lymphocyte activation: standardization and use of this model in immunocompromized elderly subjects.

Anti-T3-induced T cell activation was standardized in human peripheral blood lymphocytes with respect to dose response, time kinetics and effect of exogenous IL-2 on blastogenesis and on IL-2 receptor expression, identified by anti-Tac monoclonal antibody. IL-2 was able to significantly increase 3H-thymidine uptake and Tac antigen expression in unstimulated and anti-T3 activated lymphocytes. This enhancement was more evident in cultures stimulated with non-mitogenic concentrations of anti-T3, supporting the hypothesis that these concentrations sensitize T cells to the Tac-inducing effects of IL-2. This model of lymphocyte activation was then applied to selected immunocompromized elderly subjects. The aged subjects showed depressed blastogenetic responses and Tac antigen expression, which were not corrected by prolonging the time of cultures. Aged lymphocytes showed a good response to costimulation with anti-T3 and IL-2, suggesting that at least for the anti-T3 activation pathway they are able to respond to IL-2 signals.

Adult↗

PubMed1987

Effect of subcutaneous thymopentin treatment in drug addicts with persistent generalized lymphadenopathy.

The effect of thymopentin treatment on the immune defects in drug addicts with persistent generalized lymphadenopathy and HTLV-III infection was investigated. Thymopentin was administered subcutaneously at two different dose schedules: 50 mg three times a week for 3 weeks (first cycle) and 50 mg/week for 3 months (second cycle). After the first cycle an increased number of OKT4+ lymphocytes and an improvement of PWM-induced blastogenesis and IgG synthesis in vitro was observed. The second cycle was unable to modify the same immune parameters in vitro. The treatment had no effect on the PHA responsiveness and on PHA-induced interleukin 2 production. The significance and the prognostic value of these findings are discussed in terms of the clinical evolution of the syndrome.

AIDS-Related Complex↗

PubMed1987

Anti-mitochondrial type M5 and anti-cardiolipin antibodies in autoimmune disorders: studies on their association and cross-reactivity.

In a series of 42 positive sera, anti-mitochondrial type M5 antibodies (AMA-M5) were found most frequently in patients with SLE (24) and SLE-like syndromes. Patients with AMA-M5 displayed a higher prevalence of thrombocytopenia, thrombosis, biological false positive seroreactions for syphilis, lupus-like anticoagulant activity and anti-cardiolipin antibodies in comparison with a group of 43 SLE AMA-M5 negative patients. The strong association between anti-phospholipid and AMA-M5 antibodies cannot be explained entirely by cross-reactivity between these two groups of antibodies, as indicated by absorption experiments and studies using affinity purified antibody preparations. However, cardiolipin liposomes were able to reduce partially the titres of AMA-M5 sera, suggesting that a small population of AMA-M5 antibodies exists that cross-reacts with cardiolipin. The existence of this population was further substantiated by our demonstration that an IgM monoclonal antibody, from a patient with Waldenström's macroglobulinaemia, displayed both anti-cardiolipin and AMA-M5 activity, and AMA-M5 activity was completely inhibited by cardiolipin.

Adult↗

PubMed1986

Detection and further characterization of a newly described microsomal autoantibody associated with chronic delta infection.

Sera from 162 patients with acute or chronic hepatitis and from patients with autoimmune diseases have been investigated for autoantibodies by indirect immunofluorescence on human and animal tissues. A small proportion (14.2%) of young patients with chronic delta hepatitis has been found positive for cytoplasmic staining which was maximal in hepatocytes and renal proximal tubules. This autoantibody has been found to react with microsomal antigenic determinant different from the classic liver-kidney microsomal LKM antigen as demonstrated by fluorescence absorption experiments with purified subcellular organelles and by fluorescence-blocking tests. The microsomal autoantibody displayed also organ and species-specificity different from those shown by the LKM-positive sera. The positive patients showed persistence of the microsomal autoantibody during the follow-up without other serological markers of autoimmunity. There was no evidence of a particular course of chronic delta hepatitis in patients positive for the microsomal autoantibody.

Adolescent↗