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Biomedical subjects

F Di Padova

Publications and source records attributed to F Di Padova.

At least 37 records · Page 2Linked to original sources
PubMed1991

Interleukin 4 promotes expression of mast cell ICAM-1 antigen.

Cell recognition molecules play a crucial role in the regulation of immune cells. We recently found that mast cells (MCs) express leukocyte recognition molecules, including ICAM-1 antigen, a natural ligand of LFA-1. We here report that interleukin 4 (IL-4), a pleiotropic cytokine and mast cell differentiation factor, selectively promotes expression of surface ICAM-1 antigen and ICAM-1 mRNA in human MCs. IL-4 also up-regulates ICAM-1 antigen in cells of monocyte/macrophage lineage but has no effect on ICAM-1 antigen expressed on basophils, fibroblasts, or lymphocytes. The increase in expression of mast cell/macrophage ICAM-1 antigen induced by IL-4 may contribute to the accumulation of leukocytes and facilitate cell-contact-dependent regulation of immune cells in inflamed tissues.

Antigens, CD↗
PubMed1991

Selective and early increase of IL-1 inhibitors, IL-6 and cortisol after elective surgery.

After trauma, inflammatory, immunological and hormonal changes are well documented. Surgical intervention is a form of programmed trauma. Through the study of surgical patients, changes in early endogenous mediators of inflammation, immune response and tissue repair can be investigated. Here we analysed changes in serum levels of IL-1 inhibitors, IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha) and cortisol in patients undergoing elective surgery. C-reactive protein (CRP) was measured as a marker of the acute-phase response. Rises in serum levels of IL-1 inhibitors, IL-6 and cortisol were detected as early as 1 h after the intervention. Peak levels were reached between 2 and 5 h. Serum levels of IL-6 and cortisol remained elevated for several days implying a persistent production. Serum levels of IL-1 and TNF did not change after the intervention. CRP levels peaked on day 2. The communication system sustained by endogenous mediators is activated after surgery as shown by selective changes in IL-1 inhibitors, IL-6 and cortisol. These mediators have different kinetics in serum and IL-6 is not the only early mediator detected. Some IL-1 inhibitors might be involved in the immunological depression observed after major surgery, in the regulation of the inflammatory response or in tissue repair. IL-6 and cortisol seem to act synergistically to activate the acute-phase response. A systemic role for IL-1 and TNF is not evident, even if the possibility that these lymphokines may act locally is not ruled out.

Adult↗
PubMed1990

Human basophils express interleukin-4 receptors.

Interleukin-4 (IL-4), a multipotential lymphokine reputed to play an important role in the regulation of immune responses, interacts with a variety of hemopoietic target cells through specific cell surface membrane receptors. The present study was designed to investigate whether human basophils express IL-4 binding sites. For this purpose, basophils were enriched to homogeneity (93% and 98% purity, respectively) from the peripheral blood of two chronic granulocytic leukemia (CGL) donors using a cocktail of monoclonal antibodies (MoAbs) and complement. Purified basophils bound 125I-radiolabeled recombinant human (rh) IL-4 in a specific manner. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high affinity IL-4 binding sites (280 +/- 40 sites per cell in donor 1 and 640 +/- 45 sites per cell in donor 2) with an apparent dissociation constant, kd, of 7.12 x 10(-11) +/- 2.29 x 10(-11) and 9.55 +/- 3.5 x 10(-11) mol/L, respectively. KU812-F, a human basophil precursor cell line, was found to express a single class of 810 to 1,500 high affinity IL-4 binding sites with a kd of 2.63 to 5.54 x 10(-10) mol/L. No change in the numbers or binding constants of IL-4 receptors was found after exposure of KU812-F cells to rhIL-3 (a potent activator of basophils) for 60 minutes. No effect of rhIL-4 on 3H-thymidine uptake, release or synthesis of histamine, or expression of basophil differentiation antigens (Bsp-1, CD11b, CD25, CD40, CD54) on primary human CGL basophils or KU812-F cells was observed.

Antigens, Surface↗
PubMed1990

Structure-function analysis of human IL-6. Epitope mapping of neutralizing monoclonal antibodies with amino- and carboxyl-terminal deletion mutants.

To study the active site(s) of IL-6 we combined mutagenesis of IL-6 with epitope mapping of IL-6 specific mAb. In addition to amino-terminal deletion mutants we described previously, carboxyl-terminal deletion mutants were prepared. Functional analysis showed that deletion of only five carboxyl-terminal amino acids already reduced the bioactivity 1000-fold. A panel of mAb to IL-6 was subsequently analyzed by antibody competition experiments and binding to the amino- and carboxyl-terminal deletion mutants. On the basis of the competition experiments the six neutralizing mAb were divided in two groups (I and II). The binding pattern with the deletion mutants suggested that the region recognized by the four mAb in group I is composed of residues of amino- and carboxyl-terminus: binding of two mAb was abolished after deletion of amino acid Ala I-Ile26, of the third mAb after deletion of the four carboxyl-terminal amino acids whereas the fourth mAb did not bind to either mutant. Group II mAb retained binding to these mutants. Taken together these data suggest that in the native IL-6 molecule amino acid residues of amino and carboxyl terminus are in close proximity and that together they constitute an active site. Furthermore our data suggest that the part of the molecule recognized by group II antibodies is a second site involved in biologic activity.

Amino Acid Sequence↗
PubMed1988

Spontaneous Ig secretion and DNA synthesis in lymphoblastoid B cells appearing after surgery.

A state of immunosuppression or immunodeficiency has been described after surgical trauma. Cellular immune functions are more heavily affected. At present the relationship between these abnormalities and the increased incidence of infections in surgical patients has not been clarified. The activation of the humoral compartment and the appearance of lymphoblastoid B cells spontaneously secreting IgG and IgA have been observed in surgical patients. These cells are a marker of a recent antigenic exposure. In this study the kinetics of appearance of this B cell subset and the relationship between spontaneous Ig secretion and DNA synthesis have been analysed in six cholecystectomized patients. A peak of spontaneous IgG and IgA secretion is evident 5 and 7 days after the intervention. In some patients (two out of six) the appearance of lymphoblastoid B cells is cyclical. A second wave of spontaneous Ig secretion becomes evident 14 days after surgery. Double immunofluorescent staining of peripheral blood lymphocytes for BrdU and cytoplasmic Ig (cIg) was employed to demonstrate that a fraction of lymphoblastoid B cells is actively proliferating and that other cells negative for cIg but active in DNA synthesis appear in the circulation. These data confirm the signs of activation observed after elective surgery in otherwise healthy subjects.

Aged↗
PubMed1988

Spontaneous and polyclonal Ig secretion by circulating B cells after surgery.

Abnormalities of the immune response are commonly observed after surgery. In many cases, they are part of a physiologic rather than of a pathologic response to trauma. In this study we show that after elective surgery in otherwise healthy subjects the B cell compartment is deeply affected, as documented by the appearance, 7 days after the intervention, of circulating lymphoblastoid B cells spontaneously secreting in vitro IgG and IgA antibodies. Analogous lymphoblastoid B cells have been described after in vivo immunization and represent a sensitive marker of the B cell response against the immunizing antigen. To better understand the origin of the reaction, we have analyzed the specificity of the antibodies secreted in culture supernatants. We show that the antibody response is polyclonal, since low titers of antibodies against several different bacterial antigens--such as tetanus toxoid, pneumococcal capsular polysaccharides (PCPs), and the lipopolysaccharides (LPSs) of several enteropathogenic strains of Escherichia coli--are detected. This response seems to reflect the previous immunologic experience of the single patient and to be caused by antigens released from traumatized tissues or absorbed through breaches in skin or mucous membranes.

Adolescent↗
PubMed1986

Methyl tert-butyl ether fails to dissolve retained radiolucent common bile duct stones.

Methyl tert-butyl ether (MTBE) has been recently proposed as a new therapeutic modality for the dissolution of cholesterol gallstones. To further evaluate efficacy and tolerability of this new litholytic agent, we have administered MTBE to 3 patients with nonobstructive radiolucent common bile duct stones after recent surgery. Methyl tert-butyl ether (8-11 ml/day) was infused after aspiration of bile via a Teflon catheter inserted through the postoperative T tube. Gentle aspiration and reinfusion were performed continuously to generate stirring. The total amount of MTBE retrieved during the entire procedure was equivalent to approximately 30% of the volume infused. In all cases, MTBE failed to dissolve the radiolucent stones, which were then dissolved with continuous infusion of monooctanoin via the biliary catheter. The characteristic odor of MTBE was detected on the breath of the patients, and nausea and somnolence developed during the treatment. Serum hepatic and pancreatic enzymes did not change after MTBE. In the third subject, who received 11 ml/day of MTBE for 2 consecutive days (total of 22 ml), histologic evidence of duodenitis was found around the papilla. In our opinion, the lack of efficacy of MTBE in dissolving retained radiolucent common bile duct stones was mainly related to its leakage from the common bile duct into the duodenum and the ensuing local chemical toxicity and systemic absorption. As MTBE needs a persistent stone-solvent contact to exert its litholytic action and, at the same time, its toxicity prevents the infusion of larger doses, MTBE use should be restricted to stones placed in closed chambers, such as the gallbladder.

Aged↗
PubMed1986

Appearance of spontaneously Ig secreting B cells in human peripheral blood after surgery.

Lymphoblastoid B cells, spontaneously secreting specific antibodies of IgG and IgA classes, are constantly detected after in-vivo immunization and represent a sensitive marker of a recent antigenic exposure. In this study we demonstrate that surgical trauma is followed, at a well-defined time after surgery, by the appearance of circulating lymphoblastoid B cells spontaneously secreting IgG and IgA. The kinetics and the functional behaviour of this B cell subset are identical to those of lymphoblastoid B cells observed after in-vivo immunization. Our data indicate that surgical trauma activates a humoral immune response. Antigens released by traumatized tissues or encountered through breaches in skin or mucous membranes might initiate the reaction.

Adolescent↗
PubMed1985

Impaired antipneumococcal antibody production in patients without spleens.

Fifteen splenectomised and 15 normal subjects were studied, in absence of any intentional immunisation, for pokeweed mitogen induced synthesis of antipneumococcal capsular polysaccharide antibodies in vitro by peripheral blood mononuclear cells. Results showed that removal of the spleen had caused a persistent immune deficiency of circulating B cells capable of synthesising IgM antipneumococcal capsular polysaccharide. In vitro synthesis of polyclonal IgM and IgG by peripheral blood mononuclear cells of subjects without spleens was also depressed. These defects were due to an abnormality of the B cell compartment. These data are evidence of the major role of the spleen in the control and production of a consistent part of pokeweed mitogen responsive circulating B cells and add another facet to the complex immune dysfunction of splenectomised subjects. The findings, moreover, may help in understanding the susceptibility of splenectomised people to pneumococcal sepsis and the delayed and impaired antibody response to pneumococcal vaccine.

Adult↗
PubMed1985

Inhibition of lymphocyte function by a naturally occurring nucleoside: 5'-methylthioadenosine (MTA).

The link between immunodeficiencies and nucleoside metabolism is exemplified by the inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase which are associated with an abnormal development of the immune system. In this report we show that high doses of methylthioadenosine (MTA), a natural purine nucleoside, inhibit both the mitogen-induced blastogenesis of human peripheral blood lymphocytes (PBL) and the pokeweed mitogen (PWM)-driven in vitro immunoglobulin synthesis by PBL in a non-toxic and reversible fashion. Our data support the view that both T and B cells are sensitive to MTA inhibition and that PWM-driven Ig production is more affected by MTA than the mitogen-induced PBL proliferation. The observation that MTA causes an evident inhibition of in vitro PWM-driven Ig secretion when added four days after the start of the cultures suggests that MTA can exert its activity not only on proliferation but also on differentiation of B cells.

Adenosine↗
PubMed1985

S-adenosyl-L-methionine protection against alpha-naphthylisothiocyanate-induced cholestasis in the rat.

The effect of S-adenosyl-L-methionine (SAMe) on cholestasis induced by alpha-naphthylisothiocyanate (ANIT) was studied in rats. SAMe significantly attenuated both bile flow impairment and elevated values of serum bilirubin, glutamic pyruvic transaminase and alkaline phosphatase in ANIT-treated animals. These results suggest that SAMe protects the rat liver against the toxic effects of ANIT.

1-Naphthylisothiocyanate↗
PubMed1985

Functional and multimarker analysis of T-cell chronic lymphocytic leukaemia.

The morphology, immunophenotype, cytoenzymatic and functional activities of T lymphocytes from 4 patients with chronic lymphoproliferative disease of T-cell origin were studied. Clonal proliferation was demonstrated by distinctive chromosomal abnormalities involving chromosomes 2 and 14. Patients 1 and 2 were classifiable as OKT4+ T-cell chronic lymphocytic leukaemia (T-CLL) and patient 3 as OKT4+/OKT8+ T-CLL, with helper function in vitro only in patient 1. Patient 4 has low-grade lymphocytosis with benign clinical course, with cells showing morphology of large granular lymphocytes (LGL), and immunophenotype HNK-1+, ER+, Fc gamma receptor+, OKT3+, OKT11+ and OKT8+, as well as natural killer activity, radiosensitive suppressor activity on Ig secretion and responsiveness to PHA; this case was interpreted as LGL leukaemia. This study indicates that a large proportion of cases of true T-CLL may belong to the OKT4 subset, and that extensive investigations should be made of the lymphocytic OKT8+/T gamma forms to characterize them precisely.

Aged↗
PubMed1984

Effect of 3-hydroxy-3-methylglutaric acid administration on bile lipid composition in humans.

The effects of the lipid-lowering agent 3-hydroxy-3-methylglutaric acid (HMGA) on serum lipids and on biliary lipid composition were evaluated in a double-blind, placebo-controlled study in normolipidemic volunteers. After 4 weeks of HMGA administration (1 g three times a day orally) serum total cholesterol showed a significant decrease with regard to both pretreatment values and corresponding values of controls. The bile lipid molar percentage composition and the cholesterol saturation index showed no modification after HMGA and did not differ from the values obtained in the placebo group. These findings indicate that HMGA exerts no adverse effects on bile lipid composition in humans, differing from other hypolipidemic drugs currently in clinical use, which increase the bile cholesterol saturation index.

Adult↗
PubMed1984

Functional and morphological suppressor T cell deficit in acute GVHD.

Bone marrow transplantation (BMT) is currently used to treat patients with severe haematological disorders. One of its major complications is acute graft versus host disease (aGVHD). In this report we show that, during the early stages of lymphoid cell repopulation, an excess of suppressor T cell activity and a deficit of helper T cell activity are easily demonstrated by functional studies in healthy BMT recipients. On the contrary, in patients with active signs of aGVHD, a loss of suppressor T cells, as assessed by coculturing recipient T cells with donor B cells in an in vitro pokeweed mitogen (PWM) dependent Ig secreting assay, is detected. The loss of suppressor T cells in these patients is revealed also by the analysis of peripheral blood lymphocytes with the OKT5 suppressor cytotoxic monoclonal antibody (MoAb) but not with the OKT8 suppressor cytotoxic MoAb. Our data demonstrate that in several BMT recipients, during active aGVHD, a suppressor T cell deficit can be demonstrated both functionally and phenotypically.

Acute Disease↗
PubMed1984

S-adenosyl-L-methionine antagonizes oral contraceptive-induced bile cholesterol supersaturation in healthy women: preliminary report of a controlled randomized trial.

Recent experimental investigations have shown that S-adenosyl-L-methionine (SAMe) reverses estrogen-induced bile secretion impairment. The mechanism of this action seems to be related to the capability of SAMe both to inactivate catecholestrogens by methylation reaction and to methylate membrane phospholipids increasing the liver plasma membrane fluidity reduced by the estrogens. Aim of this investigation was to know whether SAMe also prevents oral contraceptive-induced cholesterol supersaturation of gallbladder bile in humans. To six healthy nonobese women whose bile cholesterol saturation index increased from a mean basal value of 0.77 (SD 0.22) to 1.20 (SD 0.38) (p less than 0.01) after two cycles of treatment with oral contraceptives containing 50 micrograms ethynylestradiol, plus 250 micrograms d-norgestrel, 200 mg SAMe per os tid was administered in addition to the oral contraceptive for other two cycles. The bile cholesterol saturation index decreased to 0.88 (SD 0.26) (p less than 0.05 versus oral contraceptive value). These results indicate that SAMe antagonizes biliary lipid changes induced by estrogen-progestin containing oral contraceptive and suggest its potential usefulness in women on oral contraceptive treatment to prevent lithogenic bile secretion.

Adult↗
PubMed1984

A comparative trial of desferrioxamine and hydroxychloroquine for treatment of porphyria cutanea tarda in alcoholic patients.

Forty male alcoholic patients with porphyria cutanea tarda (PCT) were randomly assigned to 2 groups of 20. The 1st group received desferrioxamine (30 mg/kg body weight/day for 1 week every 3 months) whereas the latter was given hydroxychloroquine (200 mg twice/wk orally). Alcohol abstinence was advised for all patients. Improvement of cutaneous signs was evident after 6 months in hydroxychloroquine-treated subjects and after 12 months in desferrioxamine-treated subjects. At the end of the 1-year clinical trial, significant decreases of serum iron and ferritin were found in all patients, irrespective of the therapy. Urinary total porphyrins were reduced significantly in both groups, but the drop was significantly more evident in hydroxychloroquine- than in desferrioxamine-treated subjects. After 1 year of therapy, 4 desferrioxamine-treated patients vs 16 hydroxychloroquine-treated subjects acquired a normal urinary porphyrin pattern. These results indicate that hydroxychloroquine is more effective than desferrioxamine in inducing clinical and biochemical remission of PCT. Accordingly, hydroxychloroquine should be the preferred alternative to phlebotomy, if the latter is contraindicated.

Adult↗