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Biomedical subjects

G Molinari

Publications and source records attributed to G Molinari.

At least 37 records · Page 2Linked to original sources

Protective immune response against Streptococcus pyogenes in mice after intranasal vaccination with the fibronectin-binding protein SfbI.

Despite the significant impact on human health of Streptococcus pyogenes, an efficacious vaccine has not yet been developed. Here, the potential as a vaccine candidate of a major streptococcal adhesin, the fibronectin-binding protein SfbI, was evaluated. Intranasal immunization of mice with either SfbI alone or coupled to cholera toxin B subunit (CTB) triggered efficient SfbI-specific humoral (mainly IgG) and lung mucosal (14% of total IgA) responses. CTB-immunized control mice were not protected against challenge with S. pyogenes (90%-100% lethality), whereas SfbI-vaccinated animals showed 80% and 90% protection against homologous and heterologous challenge, respectively. Multiple areas of consolidation with diffused cellular infiltrates (macrophages and neutrophils) were observed in lungs from control mice; the histologic structure was preserved in SfbI-vaccinated animals, which occasionally presented focal infiltrates confined to the perivascular, peribronchial, and subpleural areas. These results suggest that SfbI is a promising candidate for inclusion in acellular vaccines against S. pyogenes.

Adhesins, Bacterial↗

Invasion and survival of Streptococcus pyogenes in eukaryotic cells correlates with the source of the clinical isolates.

The invasiveness of 96 group A streptococci (GAS) isolates (56 from throat or skin and 40 from blood) were analyzed. GAS invasion strongly correlated with the source of the isolates, whereas no correlation was observed with the Vir type. Isolates from throat or skin exhibited the highest invasion efficiency (57% were between 0.1% and 10%). In contrast, 77.5% of the blood isolates were noninvasive (efficiency <0.01%) and only 7.5% exhibited rates comparable to those of throat or skin isolates (>0.1%). Immunofluorescence studies of 34 selected isolates showed that attachment and invasion are strain-related. Although isolates with high invasiveness usually exhibit high attachment, isolates that showed high attachment and no invasion or poor attachment and efficient internalization were identified. The ability of GAS to invade and survive within eukaryotic cells may provide bacteria a sure niche, in which they are protected against host defense mechanisms or antimicrobial agents favoring their local persistence.

Adhesins, Bacterial↗

The fibronectin-binding protein of Streptococcus pyogenes, SfbI, is involved in the internalization of group A streptococci by epithelial cells.

Streptococcus pyogenes organisms (group A streptococci) are considered to be highly adhesive extracellular pathogens. However, it has recently been reported that S. pyogenes has the capacity to efficiently invade eukaryotic cells. In this study, we demonstrate that the interaction of S. pyogenes fibronectin-binding protein (SfbI) with fibronectin on nonphagocytic HEp-2 cells triggers bacterial internalization. Blocking of the SfbI adhesin by either antibodies against the whole protein or antibodies against the fibronectin-binding domains of SfbI, as well as pretreatment of HEp-2 cells with purified SfbI protein, prevents both S. pyogenes attachment and internalization. Inert latex beads precoated with the purified SfbI protein are ingested by eukaryotic cells, demonstrating that SfbI is per se enough to trigger the internalization process. Experiments performed with a recombinant SfbI domain encompassing the two fibronectin-binding regions of the SfbI molecule demonstrated that these binding regions are essential and sufficient to activate uptake by HEp-2 cells. These results demonstrate that the fibronectin-binding protein SfbI is involved in both S. pyogenes' attachment to and ingestion by HEp-2 cells and contribute to elucidation of the underlying molecular events leading to eukaryotic cell invasion by S. pyogenes.

Adhesins, Bacterial↗

Bacteria involved in the blockage of biliary stents and their susceptibility to antibacterial agents.

Endoscopically inserted stents are used for the palliation of obstructive jaundice, but infections and blockage of these stents by biliary sludge and bacterial biofilm may develop, presenting major complications. To analyze which bacteria are involved in this process, 25 biliary stents were examined. Eighty-one microorganisms were isolated: 59 gram-negative bacteria (54 Enterobacteriaceae and 5 Pseudomonas aeruginosa), 19 gram-positive bacteria (all Enterococcus spp.), and 3 Candida albicans. The Enterobacteriaceae were sensitive to netilmicin (100%), imipenem (98%), ciprofloxacin (96%), cefotaxime (69%), and piperacillin (57%), whereas Enterococcus spp. were sensitive to imipenem (79%), piperacillin (75%), ciprofloxacin (63%), and ampicillin (58%). The unpredictable aetiology and high rates of antibiotic resistance suggest that bacteriological monitoring is mandatory to avoid treatment failures in these patients.

Adult↗

Right ventricular dysplasia as a generalized cardiomyopathy? findings on magnetic resonance imaging.

The aim of our study was to define cardiac morphological and functional abnormalities of right ventricular dysplasia by magnetic resonance imaging. Twenty-two healthy volunteers (age, 37.7 +/- 14.2 years) free of cardiac or respiratory diseases (group I) and 12 patients (age, 41.9 +/- 15.8 years) with clinical, electrophysiological and cineangiographic diagnosis of right ventricular dysplasia (group II) underwent magnetic resonance imaging at 0.2 Tesla. End-diastolic diameter, trabecular disarray and segmental wall motion abnormalities were evaluated for the right ventricle as were adipose replacement and fractional shortening for both ventricles. The right ventricular end-diastolic diameter was significantly enlarged in group II (P = 0.0023). Right ventricular trabecular disarray was mild in two group I subjects, and moderate in seven and massive in five group II patients. Right ventricular systolic bulges were found in seven group II patients, aneurysms in five. Excellent agreement was found between magnetic resonance imaging and cineangiography for bulges, aneurysms and tricuspid regurgitation (P < 0.0001). On spin-echo images, signal hyperintensities, due to adipose replacement, were found in 44 cardiac regions in group II: right ventricular outflow tract (12), sub-tricuspid posterobasal region (8), right ventricular apex (9), right ventricular anterior wall (6), interventricular septum (4), left ventricular lateral wall (4), left ventricular apex (1). Significant signal-to-noise ratio differences were found between group II abnormal areas and group I myocardial tissue for the right (P < 0.0001) and left ventricles (P = 0.0006). Fractional shortening in the right and left ventricles were significantly reduced in group II (P = 0.0002 and P = 0.00016, respectively). Magnetic resonance imaging can be considered a very useful diagnostic tool for the detection of features typical of right ventricular dysplesia, such as adipose replacement, trabecular disarray, bulges and aneurysms and provides useful information about cardiac function and regional wall motion. It indicates that left ventricular involvement occurs in a significant fraction of patients, and suggests that right ventricular dysplasia may be a generalized cardiomyopathy.

Adolescent↗

[Retrospective study of 135 cases of lung neoplasms diagnosed between 1983 and 1993].

The authors expose the results of a retrospective study concerning 135 cases of neoplasia diagnosed by their Department between 1983 and 1993. The patients' age, their sex, their consume of tobacco, their survival from the moment of the diagnosis have been considered in the study. Likewise the clinical instrumental researches and their reliability, the different incidence of the examined pathology in the first and in the second part of the period considered. It is emerged from the collected data, that also in our territory there is an increasing tendency in the incidence of lung neoplasia, a generally short survival after the diagnosis, a strong prevalence of smokers among those people affected from the disease, the difficulty of an early diagnosis due to scarce specificity of the commonest symptoms. The final auspicious is that a more incisive diligence in prevention and significant progresses in clinical pharmacological research may determine a notable reduction of the incidence of such a dramatic pathology.

Adult↗

The coronary subclavian steal syndrome: an uncommon sequel to internal mammary-coronary artery bypass surgery.

Coronary subclavian steal syndrome is a possible sequel in patients who have undergone myocardial revascularization with an internal mammary artery. We report a case of this syndrome in a 67-years-old man. In 1990 he underwent a quadruple bypass: aorta-obtuse margin, aorta-right coronary (two sequential), internal artery mammary-descending coronary artery. Three months later he started to have angina pectoris. In April 1992 an aortic arch angiography and a coronary angiography were performed. The examination showed an occlusion of the left subclavian artery at its origin. The artery was opacified countercurrently by the left vertebral artery but the left mammary artery was not opacified. Left coronary angiography showed a very severe disease of left anterior descending coronary artery and retrograde flow through the anastomosis in the left mammary artery. The patient underwent a left common carotid-subclavian artery bypass operation using a 6 mm vascutex graft. Eighteen months later the patient is doing well without angina pectoris and with very little alteration of the perfusion in the left frontal lobe observed by SPECT neuroimaging with a lipophilic tracer (99mTc-HMPAO). We think that the coronary-subclavian steal syndrome can be treated successfully with low risk by means of common carotid-subclavian artery bypass.

Aged↗

Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory concentrations of azithromycin and other macrolide antibiotics.

The ability of three macrolide antibiotics (erythromycin, clarithromycin and azithromycin) to inhibit the expression of several pathogenicity traits of Pseudomonas aeruginosa at concentrations that do not affect the rate of growth of this microorganism was investigated. Sub-MICs of azithromycin manifested the broadest spectrum of action and strongly suppressed the synthesis of elastase, proteases, lecithinase and DNase. Clarithromycin and erythromycin were far less effective. Gelatinase was reduced almost to the same level by the three antibiotics, while haemolysins and lipase were only marginally affected. Loss of motility was a strain and drug-dependent event, but all the macrolides tested shared the ability to induce this effect. However, only azithromycin totally suppressed synthesis of pyocyanin in all isolates. These results indicate that newer macrolides and especially axithromycin are endowed with a remarkable ability to inhibit in vitro the expression of a number of physiological processes that are considered more essential than replication in the pathogenesis of P. aeruginosa. Since erythromycin sub-MICs have already been shown to exert beneficial effects in clinical practice, our data, pointing to a much higher potency of azithromycin, suggest its use in future studies.

Anti-Bacterial Agents↗

Antibody responses in the serum and respiratory tract of mice following oral vaccination with liposomes coated with filamentous hemagglutinin and pertussis toxoid.

Mice were orally vaccinated with liposomes coated with filamentous hemagglutinin (FHA) and detoxified pertussis toxin (PT) of Bordetella pertussis. FHA- and PT-specific immunoglobulin G (IgG) was detected in serum, and both IgG and IgA were detected in lung washes following the immunization. Antibody responses in mice immunized with liposomes coated with FHA and PT were significantly higher than those in mice immunized with free FHA and PT, which demonstrated the adjuvanticity of the liposome carrier. The results indicate the potential usefulness of this approach for eliciting immune responses against FHA and PT (and perhaps other pertussis antigens) in humans and its possible utility in large-scale vaccination to protect against both B. pertussis infection and disease.

Adhesins, Bacterial↗

[Heart involvement in thymic neoformations: the role of magnetic resonance tomography. Experience in 3 cases].

Three paracardiac masses (1 thymic cyst, 2 thymomas) were studied by magnetic resonance imaging (MRI) using spin-echo, multi-echo, and gradient-echo sequences (cine-MR). MRI showed: a pedunculate cystic lesion, typical for thymic origin, in Case 1; cardiac and pulmonary infiltration, and 3 intracardiac metastases, in Case 2; cardiovascular compression but not infiltration, in Case 3. In 3/3 cases MRI was superior to transthoracic echocardiography (TTE), and in 2/2 MRI was superior to computed tomography (CT), not performed in Case 2 (allergy to contrast agents). MRI may be considered the most important technique to evaluate cardiovascular involvement by thymic neoplasms. MRI should be performed after TTE and makes CT unnecessary.

Adult↗