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Biomedical subjects

P L Meroni

Publications and source records attributed to P L Meroni.

At least 181 records · Page 10Linked to original sources

Secondary and essential cryoglobulinemias. Frequency, nosological classification, and long-term follow-up.

The clinical and immunochemical classification of 166 patients with cryoglobulinemia are presented. 52% of the cryoglobulins were detected in patients hospitalized because of various causes. The most frequent association was with liver and lymphoproliferative diseases (in particular with Waldenström's macroglobulinemia); two thirds of the patients with liver diseases presented with a purpura-arthralgia syndrome, and the hepatic involvement was only brought to evidence by subsequent laboratory investigation. The presence of cryoglobulins did not usually interfere with the clinical course of the basic condition. In 79 patients the cryoglobulinemia was considered idiopathic. In order to study the natural course of the disease in the idiopathic cases, a group of 35 patients had been followed up for 8-17 years: 37% developed a membranous proliferative glomerulonephritis, and more than half died of renal insufficiency; in 11% cirrhosis was diagnosed after a period of 4-9 years; another 11% developed a lymphoproliferative disease; of the remaining 40%, 2 are still asymptomatic, and the others are affected by purpura-arthralgia syndrome.

Adult↗

Effect of corticosteroids on neutrophil function: inhibition of antibody-dependent cell mediated cytotoxicity (ADCC).

Hydrocortisone sodium succinate (HC) inhibited "in vitro" neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC). The drug effect was dose-dependent and completely reversible. The killing defect was partially overcome by increasing the density of the antibody on the target cells. However, HC added after the binding between effector and target cells was still able to inhibit in a similar dose-dependent way the cytotoxic activity. Our results suggest that HC interferes in a later step, after the effector/target interaction. Methyl-prednisolone and dexamethasone as well as HC were found to inhibit in a dose-dependent manner the neutrophil-mediated ADCC, whereas testosterone did not have any effect.

Adrenal Cortex Hormones↗

Con A suppressor cell assay: a further characterization.

Con A induced suppressor cell assay was further characterized in this study. Significant lower mitogenic responses of autologous fresh cells cocultured with Con A-activated cells were found when compared with the response of cocultures of responders plus control cells preincubated in medium alone. However, Con A-activated cells did not express a real suppression, since no difference was found between responses of fresh responders alone and responses of cocultures with Con A-activated cells. So, Con A activation seemed to block the expression of the enhancement provided by control cells to autologous responders, rather than to induce a real suppressor activity. The induction of the Con A suppressor cell activity required cell proliferation but it was not proportional to the degree of DNA synthesis. Monocyte depleted cell populations exhibited lower Con A suppressor cell activity compared to unfractionated cells, suggesting a cooperative role of monocytes in the Con A induction step. The expression of this activity was not due to a cytotoxicity against the responders and was dependent on the number of activated cells added. Mononuclear cells from active lupus erythematosus (SLE) patients, but not from inactive SLE patients differed from normal controls in showing a significant loss of suppression index.

Adult↗

Defective suppressor cell activity in essential mixed cryoglobulinemia.

Peripheral blood mononuclear cells from patients with essential mixed cryoglobulinemia were investigated for the ability to induce suppressor cell activity (S.C.A.) following in vitro exposure to Concanavalin A (Con A). The generation of Con A-S.C.A. is significantly impaired in essential mixed cryoglobulinemia compared to the healthy controls. No correlation was found between Con A-S.C.A. and the clinical or laboratory parameters of the disease. This impaired ability to induce Con A-S.C.A. in essential mixed cryoglobulinemia reflects a functional T-cell defect, which may play a role in the pathogenesis of the disease.

Adult↗

Phagocytic function of polymorphonuclear leukocytes in essential mixed cryoglobulinaemia.

We have studied the phagocytic function of polymorphonuclear leukocytes obtained from 16 patients with essential mixed cryoglobulinaemia and 16 normal subjects, utilizing three different experimental models. The in vitro phagocytosis of Candida albicans by polymorphonuclear leukocytes obtained from the patients in the presence of autologous serum was subnormal as compared with controls (p less than 0.002). The neutrophil defect appeared to be cellular since: a) no effect of the patient's serum on the phagocytic capacity of normal neutrophils was demonstrable; b) the defect was not reversed when normal AB serum was used as opsonin source. The polymorphonuclear leukocytes from the same patients ingested IgG-coated sheep red blood cells to a significant higher degree than normals (p less than 0.002) when tested in patient's serum free-medium. Finally, no differences between patients and controls were observed on the basis of latex uptake. A possible explanation for these contradictory results is discussed.

Adult↗

Inhibition of polymorphonuclear leukocyte-mediated cytotoxicity by hydrocortisone "in vitro".

The effect of hydrocortisone (HC) on in vitro human polymorphonuclear leukocyte cytotoxicity was studied. HC was able to inhibit reversibly and in a dose-dependent way the antibody-dependent cellular cytotoxicity (ADCC) and the phytohemagglutinin-dependent cellular cytotoxicity (PDCC). The killing defect was partially overcome by increasing the antibody or the phytohemagglutinin (PHA) concentrations on the target cells. HC inhibited the PDCC more efficiently than ADCC; in fact the inhibition was present even at 10-5 M HC levels. Higher concentrations caused a progressive reduction in both tests. Inhibition of these PMN-mediated cytotoxicities may explain, in part, bot the anti-inflammatory actions of steroids and their deleterious effects on host defenses.

Antibody-Dependent Cell Cytotoxicity↗

Increase of T.G lymphocytes in human one-way mixed lymphocyte culture.

Human one-way mixed lymphocyte culture induces a significant increase of EA(7S) rosette-forming cells. Using fractionation procedures, an increased number of Fc receptor-bearing cells in the T high-enriched populations was found from alloactivated lymphocytes compared with similar fractions obtained after autologous control cultures. Additional experiments showed a parallel increase of E-rosette-forming cells in the Fc receptor-enriched alloactivated fractions. The results indicate that an increase of T.G lymphocytes occurs during in vitro alloactivation in man.

Cell Count↗

The role of superoxide anion generation in antibody-dependent polymorphonuclear leukocyte-mediated cytotoxicity.

Human polymorphonuclear leukocytes (PMNs) can act as killer cells in an antibody-dependent cellular cytotoxicity (ADCC) system. Cytolysis is rapid and detectable at low effector/target cell ratios. PMNs from a patient affected by chronic granulomatous disease (CGD) exhibit an absolute defect in ADCC. In order to investigate the role of the toxic oxygen derivatives (H2O2 and superoxide anions) lacking in CGD, experiments in presence of specific inhibitors were carried out. Superoxide dismutase, an O-2 scavenger, displayed a significant inhibition activity in a dose dependent way. On the other hand neither catalase, which degrades H2O2, nor sodium azide, a myeloperoxidae inhibitor, affect the cytotoxic activity. Our results suggest that the importance of the intact oxidative metabolism in PMN-mediated ADCC against chicken red blood cells could be referred to the correlated production of O-2 anions.

Animals↗

T cell defect in essential mixed cryoglobulinaemia.

Peripheral blood lymphocytes from untreated patients with essential cryoglobulinaemia were studied for their surface markers and for their in vitro mitogenic reactivity. No differences in lymphocyte subpopulations were observed between cryoglobulinaemic patients and normal controls. Cultures of separated lymphocytes were stimulated with different concentrations of phytohaemagglutinin, Con-A and pokeweed mitogen. Incorporation of [3H]-thymidine in patients' cultures was compared with that of normal controls. Significantly decreased reactivity to phytohaemagglutinin and Con-A, but not to pokeweed mitogen, was found in all patients studied. The depressed mitogenic reactivity to phytohaemagglutinin and Con-A might be referred to a qualitative T cell defect.

Adult↗

Study on the turnover of the receptor for the third component of complement on human lymphoid cells.

The in vitro turnover of the receptor for the third component of complement (C3) was studied in normal peripheral blood lymphocytes (PBL) and in lymphoblastoid cells from established cell cultures of both "normal" and "malignant" origin. The turnover was evaluated by studying i) the disappearance rate of the C3-receptor in cells in which the protein synthesis was blocked by cycloheximide and puromycin, ii) the reexpression rate of the C3-receptor after treatment of the cells with either rabbit antiserum against B lymphocytes or mouse C activated through the alternative pathway by inulin. The results show that the C3-receptor of all the lymphoid cells has roughly a half-life of about 3 to 4 hr. However, the cultured lymphoblastoid cells were less sensitive than normal PBL to inhibition by cycloheximide and showed a faster reexpression rate of the C3-receptor. A spontaneous release of the receptor was found to occur, since a receptor-like activity was detected in the spent culture medium of long-term cultured lymphoid cells.

Animals↗

Autoantibody pattern in non-A, non-B hepatitis.

Acute and convalescent sera from 44 patients with non-A, non-B hepatitis were tested for organ and non-organ specific autoantibodies by indirect immunofluorescence. In the acute-phase sera, 36.4% of the patients were positive for smooth muscle antibodies. Brush border antibodies and anti-reticulin antibodies were detected in 13.6% of the patients. Only two patients (4.5%) were positive for anti-nuclear antibodies. The autoantibody pattern did not relate to the different epidemiology, sex, a previous hepatitis B virus infection or to the biochemical liver function tests. The autoantibody pattern did not differ statistically in patients who recovered (23 cases) and in patients who progressed to chronic liver disease (21 cases), even if a higher frequency of smooth muscle antibodies was detected in the latter group. Convalescent sera screening showed that the clinical course of the disease did not relate to the behaviour of smooth muscle antibodies, brush border antibodies and anti-reticulin antibodies. However, an increase (28.6%) in anti-nuclear antibodies in patients who progressed to chronic liver disease was observed. The clinical significance of the presence of serological markers of autoimmunity in patients with chronic sequelae following acute non-A, non-B hepatitis is discussed.

Acute Disease↗

Immune complexes and IgG-Fc receptors on human platelets in essential mixed cryoglobulinemia.

An enzyme-linked immunosorbent assay (ELISA) using wells coated with normal platelets has been tested in order to quantitate cell-bound immune complexes (ICs) by measuring the uptake of alkaline phosphatase-conjugated antibodies to IgG in the immune complexes. All patients with essential mixed cryoglobulinemia had levels of serum IgG ICs above control values; a poor accordance was found between levels of ICs detected by this method and those obtained using the conglutinin method. The presence of these complexes was correlated with human platelet aggregation: platelets aggregated in vitro when cryoglobulins with higher IgG/IgM ratio were present. This type of ICs could be critical also for platelet activation and aggregation in vivo.

Antigen-Antibody Complex↗