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G Ruggiero

Publications and source records attributed to G Ruggiero.

At least 55 records · Page 3Linked to original sources
PubMed1996

CD40 expressed on thymic epithelial cells provides costimulation for proliferation but not for apoptosis of human thymocytes.

Human thymic epithelial cells express CD40, so we examined the possible role of CD40 in activation of thymocytes. We observed that both CD4+CD8- and CD4-CD8+ thymocytes proliferate after stimulation by anti-CD3 mAb in the presence of cultured thymic epithelial cells. Costimulation of CD4+ thymocytes by thymic epithelial cells is partly inhibited by an anti-CD40 mAb, but this mAb has no effect on costimulation of CD8+ thymocytes. The selective costimulatory ability of CD40 for CD4+ thymocytes was confirmed in experiments in which thymocytes were stimulated with anti-CD3 in the presence of murine P815 cells transfected with CD40 cDNA. The level of costimulation induced by P815-CD40 was comparable with that induced by P815 cells expressing CD80 (B7.1). Treatment of thymocytes with the Ca2+ ionophore ionomycin and the phorbol ester PMA or with anti-CD3 mAb resulted in up-regulation of the CD40 ligand, suggesting that this molecule is involved in CD40-mediated costimulation of human thymocytes. Costimulation of thymocytes by CD80 strongly increased anti-CD3-induced death of fetal thymocytes. In contrast, costimulation by CD40 did not increase anti-CD3-mediated apoptosis of these thymocytes. To confirm that CD40 does not affect anti-CD3-induced cell death, we established a variant of the Jurkat T leukemic cell line that constitutively expresses CD40L and analyzed the sensitivity of this cell line for activation-induced apoptosis. In contrast to CD80, CD40 failed to increase anti-CD3-mediated apoptosis in CD40L+ Jurkat cells, whereas both CD40 and CD80 strongly increased IL-2 production induced by anti-CD3. These findings suggest that costimulation by CD40 is involved in clonal expansion of CD4+ thymocytes but not in activation-induced cell death.

Antibodies, Monoclonal↗
PubMed1996

Unorthodox antibiotic combinations including ciprofloxacin against high-level gentamicin resistant enterococci.

Development of high-level gentamicin resistance among enterococci represents a serious therapeutic problem as it precludes synergy between aminoglycosides and cell-wall active agents. As part of a search for active antibiotic combinations against enterococci with high-level gentamicin resistance, we tested by the time kill curve method the efficacy of ciprofloxacin combined with ampicillin, trimethoprim-sulphamethoxazole, vancomycin or teicoplanin against ten isolates of Enterococcus faecium, three of Enterococcus casseliflavus and 13 of Enterococcus faecalis that exhibited a MIC of gentamicin > or = 2000 mg/L. Most of the E. faecium were also resistant to ampicillin and to ciprofloxacin. The combination of ciprofloxacin with ampicillin was bactericidal against five of seven E. faecium strains that exhibited a ciprofloxacin MIC < or = 4 mg/L, but was inactive against the three E. faecium that were highly resistant to ciprofloxacin. This combination was also bactericidal against the E. casseliflavus and all the E. faecalis strains. The combination of ciprofloxacin with trimethoprim-sulphamethoxazole was bactericidal against five of the seven E. faecium and seven of the nine E. faecalis strains with a ciprofloxacin MIC < or = 4 mg/L. No bactericidal activity of this combination was seen against the enterococci that were highly resistant to either ciprofloxacin or to trimethoprim-sulphamethoxazole. The combination of ciprofloxacin with glycopeptides was inactive against E. faecium and E. casseliflavus and against E. faecalis, it was either ineffective or antagonistic; in only one case it was bactericidal. Five strains of E. faecium were resistant to all antibiotic combinations tested.

Ampicillin↗
PubMed1996

Stimulation through CD50 (ICAM-3) induces both activation and programmed cell death of human thymocytes.

CD50 (ICAM-3) has been identified as the third CD11a/CD18 (LFA-1) counter receptor. We investigated the expression and possible role of this molecule in the induction of early and late activation events in human thymocytes. We observed that CD50 expression is acquired by early T cell progenitors (CD34+) and maintained during thymic development, reaching the highest levels in the most mature population of thymocytes (CD3high). Neither basal nor cytokine-induced expression of CD50 was observed on untransformed human thymic epithelial cell lines. Cross-linking of CD50 expressed on the surface of human thymocytes, by using mAbs recognizing epitopes not related to the CD11a binding site, transduced transmembrane signals leading to an increase of intracellular calcium concentration. This calcium mobilization was inhibited when CD50 was co-cross-linked with CD45, suggesting that tyrosine phosphorylation is also involved in CD50 signaling. The same anti-CD50 mAbs that were able to affect intracellular calcium levels were shown to induce CD69 but not CD25 expression on human thymocytes. This effect was preferentially observed on CD3low/CD3high thymocyte subpopulations. Cross-linking of CD50 also significantly increased activation-induced cell death of human thymocytes. These results support the idea that CD50 molecule can play a role in developing functionally mature T lymphocytes.

Antibodies, Monoclonal↗
PubMed1996

Epidemiology, clinical spectrum and prognostic value of mixed cryoglobulinaemia in hepatitis C virus patients: a prospective study.

A prospective study was undertaken to evaluate the prevalence, incidence, clinical spectrum and prognostic value of mixed cryoglobulinaemia in HCV infection. Four-hundred and thirty-two consecutive patients with chronic liver disease, 303 HCV-related, 81 HBV-related, 14 nonB-nonC related, and 34 of non-viral aetiology were studied. Cryoglobulinaemia was detected in 139 (46%) of the HCV-related chronic hepatitis patients, in 4 (5%) of the HBV-related and in none of the chronic hepatitis patients of any other aetiology. Cryoglobulinaemia was associated with liver cirrhosis, the duration of liver disease and predominantly with the female sex. HCV and anti-HCV antibodies were present in all the cryoprecipitates. All the HCV genotypes were associated with cryoglobulinaemia. In a high percentage of patients, the amount of cryoglobulinaemic was low and about half of the cryoglobulinaemic patients showed a clinical syndrome. The incidence per year of cryoglobulinaemia (6%) and of related signs was low. A higher incidence of malignant lymphoproliferative diseases was observed in type II cryoglobulinaemia. The presence of a cryoglobulinaemia-related clinical syndrome plays a role in the prognosis of patients with chronic hepatitis C.

Case-Control Studies↗
PubMed1995

Resistance to aminoglycosides and other antibiotics among clinical isolates of Enterococcus spp.

We conducted a study on 81 clinical isolates of enterococci (65 Enterococcus faecalis and 16 Enterococcus faecium) collected consecutively over a one year period at our University Hospital. Of them, 10 (15%) Enterococcus faecalis and 6 (38%) Enterococcus faecium showed high level resistance to aminoglycosides, were all acquired in surgical units and in five cases they were responsible for invasive infections. Ampicillin and imipenem were active only against Enterococcus faecalis. Vancomycin and teicoplanin were bacteriostatic; however, teicoplanin MICs were lower and in 45% of cases its MBC values were within clinically achievable serum concentrations. Ciprofloxacin and cotrimoxazole were active in vitro.

Aminoglycosides↗
PubMed1994

Prevalence of antibiotic resistance among clinical isolates of methicillin-resistant staphylococci.

The prevalence of methicillin-resistant and multiply antibiotic-resistant staphylococci causing infections in hospitalized patients was studied over a two-year period. Among 122 clinically significant staphylococci, the prevalence of methicillin resistance was 66%, with a higher prevalence of Staphylococcus haemolyticus (85%) and Staphylococcus epidermidis (83%) observed than of Staphylococcus aureus (49%). Multiple antibiotic resistance was observed more frequently among coagulase-negative staphylococcus (52 to 70%) than among Staphylococcus aureus (17%). All strains of methicillin-resistant Staphylococcus aureus were susceptible to glycopeptide antibiotics and to trimethoprim-sulfamethoxazole, whereas approximately 50% of coagulase-negative staphylococci exhibited either moderate susceptibility or resistance to teicoplanin. For these latter strains, vancomycin remains the agent of choice, whereas teicoplanin cannot be recommended unless its efficacy is established by MIC determination.

Anti-Bacterial Agents↗
PubMed1993

HLA class II molecules transduce accessory signals affecting the CD3 but not the interleukin-2 activation pathway in T blasts.

MHC class II molecules play a central role in the control of the immune response, but their biologic function and mechanism of action on the surface of activated human T lymphocytes are not entirely understood. In our study, the functional role of HLA class II molecules in T-blast proliferation was investigated by analyzing in parallel the IL-2- and CD3-driven activation pathways. The results indicate that the cross-linking of class II and CD3 molecules significantly increased the CD3-mediated T-blast proliferation, while no effect was observed on the IL-2-driven cell activation. This phenomenon was not confined to either CD4+ or CD8+ subsets nor was specifically affected by CD45 triggering. Biochemical studies showed that signaling via MHC class II molecules in T blasts led to PKC membrane translocation and IP accumulation. The simultaneous triggering of CD3 and HLA class II molecules led to a synergistic effect on IP accumulation but did not increase the CD3-mediated PKC membrane translocation. Our data suggest that HLA class II molecules are involved in T-cell-T-cell interactions and can mediate accessory signals, affecting the T-lymphocyte activation state.

CD3 Complex↗
PubMed1993

Clinical efficacy of dirithromycin versus miocamycin in tonsillopharyngitis.

A single-blind, randomized, parallel-group study was conducted to compare the efficacy and safety of dirithromycin with miocamycin in the treatment of streptococcal pharyngitis/tonsillitis caused by Group A streptococci. The study population consisted of 60 patients: 30 were randomized to receive 500 mg dirithromycin od and 30 to receive 600 mg miocamycin bd. All 30 dirithromycin-treated patients were eligible for efficacy analysis. A favourable clinical response was observed in 100% of these patients at the post-therapy visit. In the miocamycin-treated group, 28 of 30 (93.3%) patients were eligible for efficacy analysis; a favourable clinical response was observed in 100%. Bacteriological cure of evaluable dirithromycin- and miocamycin-treated patients was 96.7% and 92.9%, respectively. No statistically significant post-therapy differences in clinical or bacteriological response rates were noted between the two groups. Adverse event analysis showed no significant differences between treatment groups. There were no serious adverse events during the study. Two miocamycin-treated patients were prematurely withdrawn from the study due to adverse events (diarrhoea). Analysis of clinical laboratory data revealed no statistically significant differences between the treatment groups that were considered to be drug related. The results of this study suggest that dirithromycin has comparable safety and efficacy to miocamycin in the treatment of streptococcal pharyngitis/tonsillitis infections caused by Group A streptococci.

Adolescent↗
PubMed1992

[Usefulness and limitations of vaccination against influenza].

Influenza viruses have caused major epidemics of respiratory disease and a high mortality in patients with advanced age and in those with underlying health conditions. It has been estimated in the USA that, during a moderate epidemic of influenza, there is an excess of 170,000 hospitalizations and approximately 20,000 to 40,000 influenza-associated deaths per years. Costs may exceed 1 billion dollars per year. Influenza viruses have been difficult to control because of a large animal reservoir and of the frequent change of the virus antigenic structure by major (shift) and minor (drift) variations. Current killed trivalent vaccines are made of two influenza A subtypes plus influenza B virus. Because of the antigenic variation, vaccine composition needs to be changed almost every year in order to contain the strains most likely to be effective. There are two types of vaccines--"whole" and "split". The latter has been treated to reduce pyrogenic components and is particularly indicated in children. Vaccine efficacy varies according to how closely the immunizing strains resemble the circulating wild strain. It also depends on the viral strains which had appeared in the preceding years (herd immunity), on the number of the doses administered and on the interval between the vaccination and the natural challenge. The antibody response to vaccine is short-lived. It is greatest in normal adults and lowest in aged and in immunosuppressed patients. Vaccination reduces clinical infections by 70-80% in children and adults, but only by 30% in elderly patients living in institutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

HLA class II molecules on monocytes regulate T cell proliferation through physical interaction in the CD3 activation pathway.

HLA class II molecules are involved in the OKT3-induced T cell activation, since monoclonal antibodies (mAb) to monomorphic determinants of class II antigens are able to inhibit T cell proliferation. This effect involves several of the events leading to T cell activation and proliferation, i.e. interleukin (IL) 1, IL 6 and IL2 secretion and IL2 receptor expression. The main target of the inhibition is represented by monocytes, and the interference of anti-class II mAb in the direct interaction of monocytes with T cells is likely to play a relevant role in the inhibition mechanism. To test this hypothesis, we investigated in the present study the effect of anti-class II mAb on the proliferation of T cells stimulated with mAb OKT3 in the presence of paraformaldehyde-treated monocytes. We show that the inhibition of proliferation is specific and dose dependent, and seems to involve particular class II epitopes. Addition of fixed monocytes to inhibited T cell cultures restores proliferation to a moderate extent, only if monocytes are added within the first 12 h of culture, suggesting that class II antigens or spatially related molecules deliver signals concurrently with the mitogenic stimulus. The blocking capability of anti-class II mAb was not restricted to the CD4+ or the CD8+ T cell subsets, suggesting that, under inhibitory conditions, these mAb affect other structures on the T cell surface, relevant to the monocyte-T cell interaction.

Antibodies, Monoclonal↗
PubMed1991

Giant aneurysm of the calloso-marginal artery.

A giant aneurysm of the right callosomarginal artery is reported in a 3-month-old child. This location is rare: including our case reported here, only three cases have been described. Clinicoradiological findings are presented and the surgical procedure is illustrated.

Female↗
PubMed1991

Immunogenicity of anti-idiotypic antibodies and of their F(ab')2 fragments.

Within the idiotype/anti-idiotype network, immunoglobulins act alternatively as reactive molecules and as antigens. To investigate the antigenic properties of immunoglobulins, we evaluated the immunogenicity in rabbits of three murine monoclonal anti-idiotypic antibodies and of their F(ab')2 fragments. These antibodies, bearing the internal image of a human melanoma antigen, may be useful in view of a human therapeutic application. The effect was evaluated as specific anti-anti-idiotypic response, related to the immunogenicity of the idiotypic epitopes in the combining sites of the immunoglobulins, and as total anti-murine immunoglobulin response, which represents the recognition of all the immunological determinants of the molecule. The results showed that the administration of the F(ab')2 fragments results in either higher or similar degrees of anti-anti-idiotypic immunization, compared to those induced by the whole immunoglobulins. Nevertheless, when anti-anti-idiotypic immunogenicity was increased, the anti-murine response did not increase proportionally. This suggests that the use for in vivo administration of F(ab')2 fragments is more convenient than the use of their original molecules, since this results, at least, in a similar or eventually in an increased specific immunogenicity, while the possibility of aspecific recognition is reduced.

Animals↗
PubMed1991

Activity of aminoglycosides against phagocytosed bacteria.

The intracellular activity of streptomycin, gentamicin, and netilmicin on Escherichia coli phagocytosed by murine peritoneal macrophages was studied using a sensitive and standardized method. Intracellular activity of streptomycin and gentamicin at therapeutic concentrations was seen after 1 h of incubation of antibiotics with macrophages containing phagocytosed bacteria, whilst for netilmicin a significant intracellular activity was observed only after 3 h exposure. The activity of these antibiotics against intraphagocytic bacteria was significantly lower than that observed against extracellular bacteria. Sub-inhibitory concentrations of streptomycin were active against intracellular E. coli. Streptomycin was also active for a phagocytosed streptomycin-resistant strain of E. coli, but this activity was eliminated when the O2-dependent killing mechanisms of macrophages were inhibited by sodium fluoride. The data demonstrate that aminoglycosides may exert a dose-dependent intraphagocytic activity against E. coli that correlates with the time of incubation of the antibiotics with infected macrophages. Streptomycin appears to be the most effective agent followed by gentamicin and the least active was netilmicin. In the case of streptomycin, the intraphagocytic activity seems to be due, at least in part, to the stimulation of O2-dependent cellular microbactericidal mechanisms.

Animals↗
PubMed1990

Inhibition by anti-HLA class II monoclonal antibodies of monoclonal antibody OKT3-induced T cell proliferation. Studies at the mRNA level.

mAb to monomorphic determinants of HLA class II Ag have been shown to inhibit monocyte-dependent OKT3-induced T cell proliferation, indicating that MHC class II molecules play a regulatory role also in Ag nonrestricted, CD3-induced T cell proliferation. This effect involves several steps in the process of T cell activation and proliferation, including IL-1 beta, IL-6, and IL-2 secretion and IL-2R alpha expression. In the present study, we analyzed the effect of an anti-HLA class II mAb (Q5/6) on the mRNA expression of genes related to monocyte and T cell activation. mRNA levels for early (early c-myc, c-fos) and late (late c-myc, N-ras, c-myb) genes involved in T cell activation were determined as well as mRNA levels for IL-1 beta, IL-6, IFN-gamma, IL-2, and IL-2R alpha. The kinetics of mRNA induction for ICAM-1 was also investigated. The results show that in T lymphocytes the expression of c-fos and early c-myc mRNA was unaffected by mAb Q5/6, whereas the c-myb and N-ras mRNA levels were strongly diminished as well as those of IL-2, IL-2R alpha, and IFN-gamma mRNA. An early increase of ICAM-1 mRNA was partially inhibited. In monocytes, a marked reduction of IL-1 beta and IL-6 mRNA was found. It is concluded that the HLA class II determinant involved in the inhibition mechanism can be engaged in the control of IL-1 beta and IL-6 mRNA levels and constitute an accessory signal up-regulating IL-2 and IL-2R alpha gene activation, through a pathway not affecting c-myc and c-fos expression.

Antibodies, Monoclonal↗
PubMed1990

Monoclonal antibody OKT3-induced T cell proliferation: differential role of HLA class II determinants expressed by T cells and monocytes.

Monoclonal antibodies (MAb) to monomorphic determinants of HLA Class II antigens inhibit monocyte-dependent T cell proliferation induced by MAb OKT3 to a different extent, suggesting a differential regulatory role of the corresponding determinants in T cell proliferation. To elucidate the mechanism(s) underlying this pattern, the MAb CR10-343 and Q5/6 with high inhibitory effect and MAb CR11-462 and CR12-356 with low inhibitory effect were characterized. Cross-inhibition studies showed that the four MAb recognize distinct determinants. The determinants recognized by MAb CR10-343 and CR12-462 are spatially close. The determinants recognized by the four MAb appear to be functionally independent in MAb OKT3-induced T cell proliferation, since the inhibitory effect of the combination of MAb CR10-343 and Q5/6 and of the MAb CR11-462 and CR12-356 was additional but not synergistic. To compare the functional activity of HLA Class II determinants expressed by monocytes and by activated T cells in MAb OKT3-induced T cell proliferation, the effect of the four MAb on MAb OKT3-induced T cell proliferation in a monocyte-dependent and in a monocyte-free system was studied. Dose-response and proliferation kinetics studies showed that the four MAb display a similar inhibitory effect on MAb OKT3-induced T cell proliferation in a monocyte-free system. These results suggest fine differences in the role played by monocyte- and T cell-bound HLA Class II determinants in the regulation of MAb OKT3-induced T cell proliferation. This functional heterogeneity may enhance the flexibility of HLA Class II antigens to mediate cell-cell interactions involved in the proliferative response to a variety of mitogenic stimuli.

Antibodies, Monoclonal↗
PubMed1990

Influence of subinhibitory concentrations of loracarbef (LY 163892) and daptomycin (LY 146032) on bacterial phagocytosis, killing and serum sensitivity.

The aim of this study was to evaluate whether pre-exposure of bacteria to a subinhibitory concentration (sub-MIC) of loracarbef (LY 163892) or daptomycin (LY 146032) could modify bacterial susceptibility to serum bactericidal activity and to phagocytosis and killing by murine peritoneal macrophages and by human polymorphonuclear leucocytes. Escherichia coli, Haemophilus influenzae type b and Staphylococcus aureus grown in the presence of one quarter the MIC of loracarbef, and S. aureus exposed to one quarter the MIC of daptomycin were phagocytosed and killed in numbers significantly higher than non-exposed bacteria. Pre-exposure to loracarbef resulted in increased susceptibility of E. coli and H. influenzae type b to the bactericidal activity of antiserum, but exposure to loracarbef or daptomycin did not modify serum sensitivity of S. aureus. Loracarbef treatment and antiserum enhanced phagocytosis and killing of E. coli and H. influenzae type b to a greater extent than either antibiotic treatment or antiserum alone. These data indicate that loracarbef and daptomycin at sub-MIC enhance the susceptibility of bacterial pathogens to cellular and host defence mechanisms.

Bacteria↗