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Biomedical subjects

M Scudeletti

Publications and source records attributed to M Scudeletti.

At least 55 records · Page 3Linked to original sources
PubMed1993

Deflazacort in the treatment of haematologic disorders.

Glucocorticoids (GCs) exert different activities that are useful for the treatment of several haematologic disorders. The synergistic effect with cytotoxic drugs is important for the therapy of lymphoproliferative diseases. The inhibition of macrophages prevents acute haemolysis and platelets destruction in autoimmune disorders; moreover GCS are the most important agents for the management of vasculitis complicating cryoglobulinaemia. Deflazacort (DFZ) has similar immunomodulating effects to other GCs but, by contrast, DFZ produces less hypercalciuria and hyperglycaemia than prednisone and dexamethasone. As a result, the adverse effects of prolonged treatment are less with deflazacort. In this paper we report the results obtained with DFZ containing treatment in 27 patients affected by haematological disorders: 12 patients with advanced low or intermediate grade non Hodgkin's lymphoma submitted to 6 courses of combination chemotherapy, 10 patients with acute idiopathic thrombocytopenic purpura and 5 patients with vascular purpura secondary to type 2 cryoglobulinaemia. DFZ was substituted for prednisone or 6-methylprednisolone at a dose calculated in accordance with the PDN: DFZ ratio of 0.78. The results were in accordance within what would be expected with standard treatments containing conventional GCs, whereas in most patients, the side-effects were negligible.

Adult↗
PubMed1993

Comparison of two glucocorticoid preparations (deflazacort and prednisone) in the treatment of immune-mediated diseases.

Different glucocorticoid preparations modify the immune reaction in different ways. In this paper, the therapeutic efficacy of two glucocorticoids, deflazacort (DFZ) and prednisone (PDN), are discussed in relation to a group of 30 patients with systemic lupus erythematosus (n = 12) or rheumatoid arthritis (n = 18). The disease sub-groups were divided into two arms, one of which was treated with DFZ and one with PDN in a double-blind protocol. The results of this study indicate that DFZ and PDN induced a clinical remission within 1 month which was maintained until the 6th month. Nevertheless, certain immunological modifications, including a significant reduction of the circulating T lymphocyte level and of the CD4/CD8 ratio, which was between 1 and 1,5 during the DFC treatment and between 1 and 2 during the PDN treatment, are more pronounced and more stable with DFZ than with PDN. Moreover, DFZ has a smaller effect on calcium and glucose metabolism than PDN since the serum glucose and calcium level of patients treated with PDN increased respectively from 90 up to 130 mg/dl and from 9,5 to 11,5 mg/dl whereas those of patients treated with DFC remained within the normal range. These findings indicate that DFZ may have advantages over PDN in the treatment of immune-mediated diseases.

Adult↗
PubMed1991

Simple ELISA method for the evaluation of soluble HLA class I antigens in human serum.

A simple sandwich ELISA method has been developed for the quantification of soluble HLA class I antigens (s-HLA) in human serum. The assay utilizes the monoclonal antibody Q6/64, directed to a monomorphic determinant of the HLA alpha-chain, to capture the antigen and the biotinylated NAMB1 monoclonal antibody, directed to beta 2-microglobulin, as the detection antibody. The extract of the LG-2 lymphoid cell line and pooled sera from 100 healthy subjects are utilized as standards. The arbitrary value of 100 s-HLA Relative Units/mL (RU/mL) is given to the 1:20 dilution of pooled human sera whose optical density value corresponds to the one of the extract of 1 x 10(6) LG-2 cells (6.25 micrograms/mL protein concentration). The assay is easy to perform, specific, reproducible (intra- and inter-assay variations ranging from 3.2% to 8.87%), sensitive (detection limit of 6 RU/mL), and needs a small amount of serum (0.1 mL). The mean serum levels of s-HLA found in 100 healthy normal subjects are 41.9 +/- 13.4 RU/mL. The potential uses of the method are discussed.

Adult↗
PubMed1991

Major histocompatibility gene products and human immunodeficiency virus infection.

In the present paper we analyze the role of major histocompatibility gene products, the human leukocyte antigens, in the pathophysiology of the acquired immunodeficiency syndrome. No association has been found between human leukocyte antigen (HLA) frequencies and human immunodeficiency virus type 1 (HIV 1) infection, whereas significant associations have been reported in some populations between some HLA haplotypes and the appearance of either opportunistic infections or secondary cancers. With regard to the human leukocyte class I antigens, their role as restriction elements in presenting HIV 1 to virus-specific cytotoxic T lymphocytes seems to be established. An increase in the serum levels of their soluble forms that correlate with disease stage has also been demonstrated. These circulating molecules could interfere with the immune response to HIV 1 and could contribute to the development of the immunodeficiency. Antigenic similarities have been detected between human leukocyte class II antigens and HIV 1 envelope proteins. These homologies could explain both the presence in some HIV-positive sera of anti-HLA class II antibodies that mediate the lysis of CD4(+)-HLA class II+ T cells and the false-positive reaction of some HIV-negative sera, which contain anti-HLA class II antibodies, in tests for HIV 1 antibodies. Reduced levels of some complement factors (the human leukocyte class III antigens) have been detected in HIV-infected subjects. These defects could play a role in the progression of the disease and affect both the clearance of HIV 1 and complement-mediated antibody responses. The data reported in this review suggest that HLA antigens may be involved in several steps of the immune deficiency of HIV-infected subjects and thus contribute to the pathophysiology of acquired immunodeficiency syndrome.

Complement System Proteins↗
PubMed1989

Functional study of T lymphocyte responsiveness in patients with dementia of the Alzheimer type.

The autologous mixed lymphocyte reaction (AMLR) was used to study T lymphocytes in a group of patients with dementia of the Alzheimer type (DAT) in order to confirm the observation that their T cell proliferation in AMLR was greater than in age-matched controls, and to investigate other pathways of T cell activation, searching for correlations between immunologic and clinical findings in DAT. The mean proliferative response in AMLR was increased in patients with DAT. No differences between patients and age-matched controls were detected when other pathways of T cell activation were investigated. The degree of response in the AMLR varied among patients with DAT. This fits with the suggestion that the disorder may be a heterogeneous syndrome.

Aged↗
PubMed1988

Immunocompetence in lung cancer patients: analysis of serological and cellular parameters.

Some serological (serum immunoglobulins, circulating immune complexes, quantitative assessment of hemolytic complement activity) and cellular (total number of circulating lymphocytes as well their phenotypic and functional characterization) parameters have been analyzed in 42 patients with lung cancer of three hystologic types and in 19 healthy controls to define whether different histologic neoplasms have an impact on the host immune system. As a group, cancer patients showed 1) the presence of circulating immune complexes, in a significant percentage, within all the three groups studied; and 2) a significant reduction of lymphocytes forming E rosette. With regard to cellular immune parameters we noted that 1) T lymphocytes isolated from the peripheral blood lymphocytes (PBL) of patients with lung cancer showed a decreased capacity to express HLA-class II antigens upon phytohemogglutinin (PHA) activation in vitro; 2) PBL from lung cancer, in particular the adenocarcinoma group, failed to proliferate upon stimulation by policlonal mitogens; and 3) the autologous mixed lymphocyte reaction (MLR) of non-T/T-type was impaired in all three groups, whereas the autologous MLR of T/T-type was impaired only in the patients with squamous cell carcinoma and in those with adenocarcinoma, probably as a result of a reduced stimulatory capacity.

Adenocarcinoma↗
PubMed1987

Effects of a new heterocyclic glucocorticoid, deflazacort (DFC), on the functions of lymphocytes from patients with rheumatoid arthritis (RA).

Deflazacort (DFC) is a new glucocorticoid which, when compared with prednisone (PDN), has similar anti-inflammatory actions, but lacks several unwanted side effects on mineral and carbohydrate metabolism. DFC is more efficient than PDN in inducing immunomodulatory effects. This study concerns twelve patients with classical RA who required corticosteroid therapy because of the ineffectiveness of other drugs. Six patients received 12 mg/day of PDN from day 1 to day 21 and 15 mg/day of DFC from day 29 to day 50. The second group of six patients received DFC initially followed by the PDN dosing regimen. At various times (4, 8, 24, 48 and 72 h) after the first administration of steroid, and 7, 14 and 21 days after the beginning of the treatment with PDN or DFC the following tests were performed the phenotype of T lymphocytes isolated from peripheral blood; the evaluation of the expression of HLA Class 2 antigens by PHA primed T cells; and the analysis of cell behavior in mixed lymphocyte reactions. The data reported in this paper show that the oral administration of DFC to patients with RA affects the in vitro behavior of their lymphocytes. This immunomodulatory effect of DFC concerns both the phenotype and function of RA lymphocytes. Moreover it differs in both intensity and kinetic characteristics from the immunomodulating effect observed with PDN (control).

Arthritis, Rheumatoid↗
PubMed1986

T cells from patients with chronic liver diseases: abnormalities in PHA-induced expression of HLA class II antigens and in autologous mixed-lymphocyte reactions.

The expression of HLA Class II antigens by resting and phytohemagglutinin (PHA)-activated T cells and their functional properties in autologous mixed-lymphocyte reactions (MLR) were investigated in patients with chronic active hepatitis, with alcoholic cirrhosis, and with primary biliary cirrhosis. In all groups of patients the percentage of resting T cells expressing HLA Class II antigens was significantly higher than that in controls. The percentage of T cells which acquired HLA Class II antigens following PHA stimulation was reduced in patients with chronic active hepatitis, serum hepatitis B surface antigen (HBsAg) positive, and in those with alcoholic cirrhosis, HBsAg negative, although the level of [3H] thymidine incorporation was within normal limits. The degree of proliferation in autologous MLR with PHA-T cells was significantly reduced in patients with chronic active hepatitis, HBsAb positive, and in those with alcoholic cirrhosis, HBsAg positive. A reduced proliferation was also detected in autologous MLR with non-T cells, in patients with chronic active hepatitis, HBsAg positive. The abnormalities of autologous MLR are selective, since the proliferative and stimulatory activities of cells from patients with chronic liver diseases in allogeneic MLR were within normal ranges. The immunoregulatory role of HLA Class II antigens and of autologous MLR suggests that the abnormalities we have identified may play a role in the immunological dysfunctions underlying chronic liver diseases.

Adult↗
PubMed1986

PHA-T cells in systemic lupus erythematosus and in rheumatoid arthritis: abnormalities in HLA class II antigen induction and in autologous mixed lymphocyte reactions.

Analysis of T cells from patients with systemic lupus erythematosus (SLE) and with rheumatoid arthritis (RA) identified a deficit in the induction of HLA Class II antigens by PHA although the proliferative response was normal and in the [3H]thymidine incorporation in autologous mixed lymphocyte reactions (MLR) with PHA-T cells as stimulators. In RA these abnormalities were more marked in patients with active disease than in those in clinical remission. The deficit of autologous MLR with PHA-T cells was more marked than that of autologous MLR with non-T cells and of allogeneic MLR. Serum from patients with SLE and with RA did not display any detectable inhibitory activity on the induction of HLA Class II antigens by PHA, on the proliferative response of lymphocytes to PHA, on autologous MLR with PHA-T cells and with non-T cells as stimulators and on allogeneic MLR. These results suggest that the abnormalities we have identified reflect an intrinsic defect of T cells.

Antibodies, Monoclonal↗
PubMed1986

The effects of a new phthalazine derivative (MDL 899) on human lymphocyte functions.

MDL-899 is new phthalazine derivative which has been developed as a substitute for hydralazine, which has several undesirable effects, in the treatment of hypertension. The effects of MDL-899 on human lymphocyte functions are analyzed. This drug inhibited in a dose-related fashion the blastogenesis of lymphocytes upon PHA and Con A activation and down-regulated the activation of allogeneic mixed lymphocyte reactions (MLR). On the contrary the drug enhanced the activation of autologous MLR of non T/T type. This effect was five times higher on cells which carried the HLA DR 4 phenotype. The above reported observations suggest that MDL-899, as well as hydralazine, affects the in vitro responsiveness of human lymphocytes mostly in subjects with HLA-DR 4 phenotype. Whether the impact of MDL-899 on immune function gives rise to a lupus like syndrome is not known. For this reason further studies are warranted to assess its long-term in vivo effects.

Antibodies, Monoclonal↗
PubMed1985

Analysis of the role of xenogeneic antigens in the proliferation of human T cells stimulated with autologous non-T cells and phytohemagglutinin-activated T cells.

Since conflicting results have been reported about the role of xenoantigens in the proliferation of T cells stimulated with autologous non-T cells, the effect of the exposure of cells to xenogeneic proteins during the isolation procedure and/or the culture period on autologous mixed lymphocyte reactions (AMLR) with non-T cells and phytohemagglutinin-activated T cells as stimulators was investigated. T and non-T cells were isolated by rosetting with 2-aminoethylisothiuronium bromide-treated sheep red blood cells (AET-SRBC), by nylon-wool filtration, and by positive or negative selection with anti-class II HLA antigens and anti-T-cell monoclonal antibodies. Isolation and cultures were performed in presence of fetal calf serum (FCS) or of autologous serum. In both types of AMLR, proliferation of responding cells did not require exposure to xenoantigens. However xenoantigens enhanced the proliferation of cells from some, although not all, the donors tested. There were differences in the degree of proliferation of the cells from the donors tested, but without correlation with the two types of AMLR. These results suggest that both types of AMLR reflect a self-recognition event and not a response to xenoantigens. However the potential interference of xenoantigens, as well as the individual variability, should be taken into account when interpreting the significance of abnormalities of AMLR in immunopathologic processes.

Antibodies, Monoclonal↗
PubMed1985

Lymphocytapheresis in the treatment of rheumatoid arthritis: clinical and immunological studies.

Six patients with Rheumatoid Arthritis (RA) have been treated with lymphocytapheresis after their disease proved unresponsive to conventional therapy. Clinical improvement, measured evaluating articular swelling, morning stiffness, and muscle weakness, was observed in four of the six patients. From the cellular point of view lymphocytapheresis induced (1) T cell depletion without modification of lymphocyte subsets in the peripheral blood, (2) improvement of lymphocyte responsiveness to lectins, autoantigens and alloantigens. All together these data suggest that therapeutic leukapheresis modifies the immune responsiveness in humans, possibly facilitating the process of cell to cell cooperation.

Arthritis, Rheumatoid↗
PubMed1984

Human T cells in cord blood: abnormalities in IA antigens induction by phytohemagglutinin and in autologous mixed lymphocyte reactions.

About 25% of human T cells isolated from cord blood acquired la antigens, following stimulation with phytohemagglutinin (PHA) for 72 hr. This percentage is markedly lower than that found in PHA-activated T-cell populations (PHA-T cells) isolated from peripheral blood of adults. The low expression of la antigens by human T cells from cord blood does not reflect abnormalities in the sensitivity to PHA stimulation and/or in the kinetics of induction of la antigens. PHA-T cells from cord blood display a low stimulatory activity in autologous mixed lymphocyte reactions (MLR). The defect does not reflect a nonspecific abnormality in the stimulatory activity of PHA-T cells from cord blood, since the latter do not differ from PHA-T cells from adults in their ability to stimulate allogeneic T cells from adults. Furthermore the defect does not reflect a nonspecific abnormality in the proliferative response of T cells from cord blood, since the latter display a normal proliferative response to PHA-T cells from adults. The defect in the proliferative response is not restricted to the autologous MLR with PHA-T cells, since it was found also in autologous MLR with non-T cells as stimulators. Correlation of the temporal evolution of the abnormalities of human T cells with the maturation of the immune system may contribute to our understanding of the role of la antigens in cell-cell interactions and of the biological significance of abnormalities of autologous MLR.

Cells, Cultured↗
PubMed1984

Role of normal adherent cells in the regulation of the autologous mixed lymphocyte reactions in humans.

The effect of normal adherent suppressor cells on the blastogenesis of human T lymphocytes in the mixed lymphocyte reaction (MLR) was studied in both allogeneic and autologous combinations. Non-T cells and Ia+ T lymphocytes were used as stimulator cells in both allogeneic and autologous MLR. The addition of adherent cells to the stimulators inhibited blastogenesis of T lymphocytes in both types of MLR when the stimulator population was made up of non-T lymphocytes but did not interfere with blastogenesis when Ia+ T lymphocytes were used as stimulator cells. The present data indicate that the T lymphocytes able to respond to Ia+ T cells (in the MLR, autologous or allogeneic) may be different from those which respond to non-T lymphocytes or may be less sensitive to the regulatory function of normal adherent cells.

Cell Adhesion↗
PubMed1984

Effect of single oral doses of prednisone and deflazacort on human lymphocyte distribution and functions. Analysis with monoclonal antibodies.

Two corticosteroids, prednisone and deflazacort, have been compared with respect to their capacity of inducing redistribution of T lymphocyte subsets, modification of expression of Ia antigens by PHA primed T cells, and inhibition of blastogenesis of T cells in autologous mixed lymphocyte reactions. Both corticosteroids were able to induce T lymphocytes depletion, increase of suppressor T cells, inhibit Ia expression upon mitogenic activation of T lymphocytes, and inhibit autologous MLRs either when non T cells or when PHA T lymphocytes were used as stimulators. We conclude that deflazacort may constitute a better glucocorticoid than prednisone for correcting the imbalance among T cells subsets, the helper T cells activity and the processes of cell-to-cell cooperation in immune diseases.

Adult↗