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Biomedical subjects

G Ruggiero

Publications and source records attributed to G Ruggiero.

At least 73 records · Page 4Linked to original sources

Structure of (+-)-6-methyl-6,12-methano-6H,12H,13H-[1]benzopyran[4,3-d] [1,3]benzodioxocin-13-one.

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.

Chemical Phenomena↗

Intracellular activity of cefamandole and aztreonam against phagocytosed Escherichia coli and Staphylococcus aureus.

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.

Animals↗

Prognostic significance of circulating immune complexes in a long-term follow-up of breast cancer patients.

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.

Antigen-Antibody Complex↗

Kinetics of phagocytosis and killing of E. coli by murine macrophages in presence of different serum preparations.

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.

Animals↗

Inhibition by anti-HLA class II monoclonal antibodies of monocyte-dependent T cell proliferation induced by monoclonal antibody OKT3.

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.

Antibodies, Monoclonal↗

Presence of endotoxemia and its relationship to liver dysfunction in patients with typhoid fever.

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.

Adolescent↗

Fifty-five thousand cerebral angiographies.

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.

Cerebral Angiography↗

HLA and prognostic factors in primary breast cancer.

A group of 157 women with primary breast cancer (BC) were typed for HLA antigens, and gene frequencies were compared to those of 327 control healthy individuals. Diagnosis of BC was made for all patients on surgical mastectomy specimens; histologic grading, estrogen (ER) and progesterone (PgR) receptors were determined on all primary tumors. Typed antigens included the majority of the specificities controlled by the HLA-A, -B and -C loci, according to the 8th International Histocompatibility Testing Workshop recommendations. No significant discrepancy in their frequencies was found in the undivided sample as compared to controls. The analysis of HLA gene frequency was extended to subsets of patients identified by the following prognostic features: (a) age at tumor diagnosis (pre-menopause vs. post-menopause); (b) receptor status (presence vs. absence of ER and PgR); (c) mammary gland dysplasia (presence vs. absence); (d) histologic grade (grade 3 vs. grades 1 and 2 combined); (e) time to relapse before or after 24 months following mastectomy). A moderate deviation from normal of some genes was found in several subsets, often affecting only one of the antithetical subgroups (feature present vs. feature absent). In the instance of B5, the increase in frequency of the gene in one of the subset pair (ER + subjects) was balanced by a decrease of the same gene in the counterpart (ER-subjects). Increased frequencies were found for the B7 gene in the following prognostic groups: (a) lack of ER (0.08); (b) lack of PgR (0.09); (c) absence of mammary dysplasia (0.075); (d) histologic grade 3 (0.10); and (e) premenopause (0.12), the last two showing significant divergence from normal. When features (d) and (e) on the one hand and (a), (b), (d) and (e) on the other were combined, B7 reached frequencies of 0.18 (p less than 5 X 10(-4] and of 0.29 (p less than 5 X 10(-6], respectively.

Adult↗

Liver disease in hemophiliacs: etiological and biochemical data on 159 cases from our geographical area.

A total of 159 hemophiliacs (149 treated) from our geographical area were screened in 1983 for serological evidence of HBV infection and biochemical evidence of liver disease. All were asymptomatic. HBsAg was detected in 16 cases (10%); anti-HBs and anti-HBc in 106 (67%); 19 (12%) subjects were susceptible to HBV. The HBV infection rate evaluated in 70 patients followed-up from 1980 to 1983 was 28% per year. The cumulative risk of HBV infection as well as the rate of seroconversion to HBV increased with increasing age and with increasing frequency of treatment given during the last 12 months. Anti-delta was detected in the serum of 5 (28%) out of 13 HBsAg-positive cases. Follow-up data showed that in 61% of subjects with liver dysfunction, hepatic damage could not be accounted for by HBV infection. AST and/or gamma-globulin increase was detected in 80% of patients. Abnormalities were more pronounced in HBsAg-positive cases and among them in subjects carrying anti-delta. Further follow-up studies are needed to clarify the long-term prognosis of liver disease in hemophiliacs.

Adolescent↗

Effect of beta-lactam antibiotics at subinhibitory concentrations on the phagocytosis of Staphylococcus aureus by the perfused rat liver.

We evaluated whether the exposure of Staphylococcus aureus to a subinhibitory concentration of penicillin and cefamandole could modify its susceptibility to rat serum factors and to the phagocytic activity of the isolated and perfused rat liver. Control or sub-MIC treated bacteria were added to the circulating medium which contained homologous serum, and the disappearance of bacteria from the perfusate and their recovery in the liver was determined during the 10 min experimental time. Sub-MIC treated bacteria were more susceptible to the bactericidal activity of serum present in the perfusate. However, the clearance rate of bacteria by the liver was decreased for penicillin-treated organisms and unchanged for cefamandole-treated bacteria. The data suggest that beta-lactam antibiotics at sub-MIC levels may modify S. aureus susceptibility to host defense mechanisms.

Animals↗

[Effect of amphotericin B on phagocytosis and intracellular killing of E. coli by rat liver perfused in vitro: preliminary results].

Using isolated and perfused rat livers we found an inhibitory effect on intracellular killing of hepatic macrophages versus E. coli, in presence of therapeutic levels of amphotericin B (5 micrograms/ml). Since an interference of this antibiotic with phagocytic functions of human neutrophils has also been reported, we suggest that amphotericin B may exert a toxic effect on intraphagocytic microbicidal function, possibly by an interaction with membrane sterols.

Amphotericin B↗

[Bactericidal activity of the serum against Staphylococcus aureus grown in the presence of subinhibitory doses of cefamandole and gentamicin].

Growth of S. aureus in the presence of subinhibitory concentrations of cefamandole alone (at 1/5 the MIC) or with gentamicin (both at 1/5 the MIC) produced large, globular cells with reduced viability (50%) as compared to untreated bacteria. Gentamicin (1/5 the MIC) did not modify bacteria and also reduced viability of inoculum (57% vs. controls). Cefamandole treated bacteria were more susceptible to the rat serum bactericidal activity then control bacteria. The growth of S. aureus in the presence of cefamandole plus gentamicin did not modify further bacterial susceptibility to serum opsonins. The data suggest that even at subinhibitory concentrations cefamandole may exert an antibacterial effect by acting in cooperation with serum factors.

Animals↗

Increased phagocytosis and killing of Escherichia coli treated with subinhibitory concentrations of cefamandole and gentamicin in isolated rat livers.

Our purpose was to study whether treatment of Escherichia coli with subinhibitory concentrations of either cefamandole or gentamicin could change bacterial susceptibility to the serum bactericidal effect and to the phagocytic and killing activity of the rat liver reticuloendothelial system. Bacteria were grown overnight with 1/5 or 1/10 of the MIC of each antibiotic. At one-fifth of the MIC, cefamandole induced filamentous elongated bacteria whose viability was decreased by 75%. The susceptibility of control and antibiotic-treated bacteria to serum was tested by measuring the survival of organisms exposed to different concentrations of rat serum in vitro. Susceptibility of bacteria to hepatic macrophage activity was tested by following the hepatic clearance of bacteria after they were added to the perfusate of the isolated rat liver. E. coli treated with subinhibitory concentrations of cefamandole or gentamicin appeared somewhat more resistant to the lytic activity of serum at a concentration of 4%, but not at 20%. Bacteria treated with 1/5 or 1/10 of the MIC of cefamandole or with 1/5 of the MIC of gentamicin were significantly more susceptible to phagocytosis and to the bactericidal activity of liver macrophages. Cefamandole appeared more potent than gentamicin in inducing these effects. The results suggest that subinhibitory levels of antibiotics may alter bacterial cell surface (cefamandole) or may impair the expression of antiphagocytic material (gentamicin), thus favoring phagocytosis and killing by macrophages. Our study provides evidence that antibiotics at subinhibitory concentrations may cooperate with host defence mechanisms against bacterial infections.

Animals↗