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Biomedical subjects

P L Meroni

Publications and source records attributed to P L Meroni.

At least 163 records · Page 9Linked to original sources

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↗

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↗

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↗

Antibodies to cardiac Purkinje cells: further characterization in autoimmune diseases and atrioventricular heart block.

We confirmed the occurrence of IgG antibodies reacting with ox cardiac conducting tissue in the serum of some human subjects. These antibodies failed to react with all ox cardiac conducting tissue cells; they reacted only with the cells defined as Purkinje cells. Having checked 352 sera, we found that the prevalence of antibodies to Purkinje cells was 11% in normal subjects (no correlation with sex and age), 14% in systemic lupus erythematosus, 21% in rheumatoid arthritis, 18% in progressive systemic sclerosis, and 23% in Sjögren syndrome. In 50 patients with permanent pacemakers for chronic non-postinfarction atrioventricular (AV) block the prevalence was 30% (P = 0.008). In a selected set of 29 patients with clinically idiopathic AV block located at or below the level of the His bundle the prevalence was 34.5% (P = 0.006). The possible role of anti-Purkinje cell antibodies in autoimmune damage of cardiac conduction tissue is discussed.

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

In vitro synthesis of IgM rheumatoid factor by lymphocytes from patients with essential mixed cryoglobulinemia.

Peripheral blood mononuclear cells (PBMC) from patients with Essential Mixed Cryoglobulinemia (EMC) were studied for their ability to synthesize polyclonal IgM and rheumatoid factor (RF) IgM in vitro. Our results indicate: that EMC-PBMC produce smaller amounts of polyclonal IgM but higher quantities of IgM-RF than normal PBMC after pokeweed mitogen (PWM) or Staphylococcus aureus activation, so that the IgM-RF to total IgM ratio is significantly greater in EMC than in normal cultures; that enriched EMC-B lymphocytes display a significantly higher spontaneous synthesis of IgM-RF than normal B lymphocytes and that the IgM-RF B cell clones are receptive to T cell regulation. Taken together these findings suggest an expansion of B cell clones committed to IgM RF production and the presence in peripheral blood of differentiated B lymphocytes capable of secreting IgM-RF in EMC.

Adult↗

Persistent generalized lymphadenopathy in drug addicts: immunological studies.

The persistent generalized lymphadenopathy (PGL) in drug addicts displays the same immunological abnormalities previously found in homosexual and haemophiliac men with PGL: impaired in vivo and in vitro T cell functions, inverted T4/T8 ratio in blood and B cell abnormalities. The peripheral blood B-lymphocytes, in fact, show a reduced in vitro immunoglobulin synthesis after pokeweed mitogen and Staphylococcus aureus activation, with an increased spontaneous IgG secretion. In the lymph node biopsies, the immuno-histological studies reveal an infiltration of OKT8 positive cells in the germinal centers, a depletion of OKT4 positive lymphocytes slighter than in the blood and an explosive follicular hyperplasia with a striking destruction of the dendritic reticulum cell framework. This latter finding, together with the high levels of serum IgG and the presence of preactivated B cells in the blood, seems to be consistent with the presence of an in vivo polyclonal B cell activation. A high incidence of anti-HTLV III antibodies was also found in the PGL drug addicts. The significance of these findings is discussed in this report.

Adult↗

In vitro immunoglobulin synthesis: T-cell requirement in pokeweed and staphylococcus aureus B-cell activation.

The T-cell requirement for the B-lymphocyte immunoglobulin synthesis induced by Pokeweed mitogen (PWM) and by Staphylococcus aureus Cowan I (SAC) was investigated. We found that the PWM induced B-cell activation was controlled by an absolute Mitomycin-C resistant T-cell helper activity and by a Mitomycin-C sensible T-cell suppressor activity. On the other hand the SAC induced B-cell activation was less thymus dependent and was not influenced by Mitomycin-C treated or irradiated T cells. The different T-cell requirement could be an expression of different responding B-cell subpopulations.

Adult↗

Anti-ribosomal ribonucleoprotein autoantibodies in systemic lupus erythematosus.

Sera from systemic lupus erythematosus (SLE) patients giving a fluorescent ribosomal pattern on tissue and cell preparations also showed precipitating autoantibodies against purified rat liver ribosomes. Ribosomal antigen is also present in rabbit thymus cellular extract (RTE), since the same sera gave precipitin lines against RTE in identity with ribosomes. Immunofluorescent staining was completely inhibited by serum absorption with ribosomes or with RTE. However ribosomal RNA and RNase or trypsin-treated ribosomes failed to react with these autoantibodies as demonstrated in immunoabsorption and immunodiffusion studies. These data suggest that these sera contain autoantibodies directed against some antigenic site composed of a portion of both RNA and ribosomal protein. Ribosomal autoantibodies were detectable at a low frequency in SLE patients characterized by an active disease and renal involvement.

Antigens↗

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from patients with essential mixed cryoglobulinemia.

Peripheral blood mononuclear cells from patients with essential mixed cryoglobulinemia (EMC) were studied for their ability to differentiate into cells containing cytoplasmic immunoglobulins (Ig) and to synthetize Ig after in vitro pokeweed mitogen activation. EMC lymphocytes showed a significant defective differentiation and Ig synthesis compared to normal controls. Coculture experiments carried out mixing enriched normal T- and EMC B-cell suspensions, and vice versa, showed that (a) the EMC B-cell-defective Ig synthesis still persisted after removal of suppressor activity by irradiation, both with autologous and with normal allogeneic T suspensions and (b) EMC T cells displayed a less efficient activity in helping Ig production by normal B lymphocytes. A comparable, reduced response was also found after activation with Staphylococcus aureus strain Cowan I. Taken together these results seem to indicate that in essential mixed cryoglobulinemia an impaired T-cell helper activity coexists with a B-lymphocyte impairment. The significance of these abnormalities in the pathogenesis of EMC is discussed.

Adult↗

Altered expression of B lymphocyte surface immunoglobulins in minimal change nephrotic syndrome and focal glomerulosclerosis.

In 20 patients with nephrotic syndrome (10 minimal change glomerulonephritis, MCN; 10 focal glomerulosclerosis, FGS) the peripheral blood lymphocytes showed a statistically significant increase in IgG-bearing cells (SIgG-C) in comparison with 30 patients with other histological types of primary glomerulonephritis with and without nephrotic syndrome (14 and 16, respectively). In the same MCN and FGS patients the serum IgG levels were slightly decreased. Furthermore, 5 cases of MCN in sustained remission for 1 year after steroid therapy showed normalization of the SIgG-C and the serum IgG levels. The possible significance of these phenomena in the pathogenesis of the hypo-IgG-globulinemia in MCN and FGS is discussed.

Adolescent↗