Biomedical subjects
Publications and source records attributed to G Ruggiero.
A six-month analysis of a controlled trial on the treatment of chronic hepatitis B in children shows that prednisone priming followed by alpha-interferon 2A was effective in 6 of 9 treated patients in reducing HBV replication and disease activity.
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)
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.
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.
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.
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.
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.
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.
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.
A derivative of warfarin, racemic C19H14O4, Mr = 306.32, monoclinic, Cc, a = 9.594 (2), b = 20.437 (4), c = 7.793 (2) A, beta = 109.94 (3) degree, V = 1436.4 (11) A3, Z = 4, Dx = 1.416 g cm-3, lambda(CuK alpha) = 1.5418 A, mu = 7.742 cm-1, F(000) = 640, T = 293 K, final R = 0.053 for 1224 observations. The title molecule, formed by spontaneous dehydration of 2'-hydroxy-warfarin, is a cyclic ketal in which the side-chain phenyl is disposed pseudoaxially and is linked through a 2'-oxygen to the ketal carbon in a fixed cis 1,3-diaxial configuration. Two dihydropyran rings are formed; one fused with the benzopyran ring adopts an e,f-diplanar conformation, the other is a chroman and is in a similar conformation.
The intracellular activity of cefamandole and aztreonam against phagocytosed Escherichia coli and cefamandole against phagocytosed Staphylococcus aureus was studied using a sensitive and standardized method of murine peritoneal macrophages. Cefamandole and aztreonam exerted an intracellular antibacterial activity against E. coli which was greater than their extracellular one. With concentrations of both antibiotics up to 16 x MBC a dose-dependent decrease of the initial number of intracellular E. coli which ranged from 32% to 90% was observed. However, similar antibiotic concentrations above the MBC affected the viability of extracellular E. coli by only 20% to 30%. The intracellular antibacterial activity of both antibiotics against E. coli was further enhanced by immune serum. Cefamandole at 4 x the MBC did not affect the survival of intracellular S. aureus, but killed 41% of extracellular bacteria by 1 h and 99% after 3 h. The intracellular activity of both antibiotics against E. coli was also maintained in NaF-pulsed macrophages which have an impaired oxidative metabolism. The data suggest that both cefamandole and aztreonam possess an intracellular antibacterial activity against E. coli that seems at least in part due to a positive cooperation of antibiotics with the O2-independent microbicidal system of macrophages.
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The purpose of the present study was to investigate the prognostic value of circulating immune complexes (CIC) in surgically treated breast cancer patients as compared with other well-known prognostic factors. CIC of IgG and IgM classes were determined by a C1q immunoenzymatic assay in serum samples of 122 patients before mastectomy and 51 of them were found positive for IgG. The other class of CIC was virtually absent. No relevant differences of distribution of other prognostic parameters such as estrogen and progesterone receptors, histological grading, nodal and menopausal status were found according to CIC levels. Level of IgG CIC was affected by surgical removal of the tumor since significant reduction of it was observed 2 weeks after mastectomy; however, this reduction did not show prognostic significance. The patients included in the present study were subjected to a 7-year follow-up; eventually a significant association was observed between preoperative IgG CIC and relapse of the disease. Patients with positive values of immune complexes relapsed more frequently than those with negative values. Serial determinations of IgG CIC were carried out within the 24 months following mastectomy and statistically evaluated for their prognostic use. No significant association was found between increase of IgG CIC level and relapse of the disease.
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In this study we evaluated the kinetics of phagocytosis and killing of E. coli by thioglycollate-elicited murine peritoneal macrophages and the role of specific antibodies and complement present in different serum preparations in modulating these processes. In our system phagocytosis of E. coli by macrophage monolayer was exponential for 180 min. The killing activity was high in the first 30-60 min and then virtually ceased. The least phagocytosis and killing occurred in presence of heat-inactivated fetal calf serum (HFCS). These activities were 2-fold increased in presence of normal mouse serum (NMS) or heat-inactivated newborn calf serum (HNCS) and were highly stimulated in presence of immune mouse serum (IMS). IMS without complement was less efficient in enhancing phagocytosis and killing by macrophages. However when IMS or HNCS were deprived of specific antibodies their activity was remarkably reduced. When macrophages containing phagocytized bacteria were reincubated with different sera, multiplication of intracellular E. coli occurred with HFCS, NMS or antibody-deprived IMS or HNCS. In contrast, a significant decrease in the survival of intracellular bacteria was seen in presence of IMS, HNCS or complement-deprived IMS. The results indicated that specific bacterial antibodies play a major role in the phagocytic process and in the activation of killing mechanisms. However optimal macrophage activity resulted from the presence of both specific antibodies and complement.
The inhibitory effect of monoclonal antibodies (mAb) to monomorphic (locus-restricted and locus-shared) and polymorphic determinants of HLA class II antigens on the monocyte-dependent proliferation of T cells stimulated with mAb OKT3 has been studied. The effect appears to be specific, dose dependent, is not mediated by the Fc portion of mAb and reflects their interaction with the corresponding determinants. The anti-HLA class II mAb do not have to be present in the culture throughout the incubation period, but are essential in early phases of mAb OKT3 T cell activation. Both monocytes and T cells are the targets of the inhibition exerted by the anti-HLA class II mAb. Their inhibitory effect involves several steps in the sequence of events which leads to T cell proliferation, including interleukin (IL) 1 and 2 secretion, and IL2 receptor expression.
Twenty-one patients with typhoid fever were studied to evaluate the presence of endotoxin in peripheral blood and its relationship to the incidence and features of hepatic dysfunction which may occur during this disease. The limulus test for endotoxin was positive in the plasma samples of all patients prior to treatment. Liver dysfunction, as assessed by fasting and postprandial serum bile acid levels and by standard biochemical tests, occurred in 90% of patients. In seven, the injury was purely cholestatic (elevation of postprandial serum bile acid levels, alone); in 12, it was of mixed cholestatic-hepatocellular type (elevation of both serum bile acids and aminotransferase levels). After recovering, the limulus test was negative and liver function tests returned to normal values in all patients. The results demonstrate that endotoxemia is present in patients with typhoid fever. In addition, since endotoxin can impair bile secretion, our results suggest that endotoxin may have a pathogenetic role in the development of liver injury during typhoid fever.
A large series of patients submitted to cerebral angiography at the Bellaria Hospital in Bologna are presented in a preliminary report. Experience gained is discussed from the standpoints of success versus failure and of the complications. It is concluded that direct percutaneous cerebral angiography, if used selectively, still has a role to fill in a modern neuroradiology department, because of its safety. It is especially well suited for the examination of older patients. For angiography of the external carotid and the vertebral artery femoral catheterization is more suitable.