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Biomedical subjects

G Molinari

Publications and source records attributed to G Molinari.

At least 19 recordsLinked to original sources
PubMed2005

Interactions between ephrin-B and metabotropic glutamate 1 receptors in brain tissue and cultured neurons.

We examined the interaction between ephrins and metabotropic glutamate (mGlu) receptors in the developing brain and cultured neurons. EphrinB2 coimmunoprecipitated with mGlu1a receptors, in all of the brain regions examined, and with mGlu5 receptors in the corpus striatum. In striatal slices, activation of ephrinB2 by a clustered form of its target receptor, EphB1, amplified the mGlu receptor-mediated stimulation of polyphosphoinositide (PI) hydrolysis. This effect was abolished in slices treated with mGlu1 or NMDA receptor antagonists but was not affected by pharmacological blockade of mGlu5 receptors. An interaction among ephrinB2, mGlu1 receptor, and NMDA was supported by the following observations: (1) the NR1 subunit of NMDA receptors coimmunoprecipitated with mGlu1a receptors and ephrinB2 in striatal lysates; (2) clustered EphB1 amplified excitatory amino acid-stimulated PI hydrolysis in cultured granule cells grown under conditions that favored the expression of mGlu1a receptors; and (3) clustered EphB1 amplified the enhancing effect of mGlu receptor agonists on NMDA toxicity in cortical cultures, and its action was sensitive to mGlu1 receptor antagonists. Finally, fluorescence resonance energy transfer and coclustering analysis in human embryonic kidney 293 cells excluded a physical interaction between ephrinB2 and mGlu1a (or mGlu5 receptors). A functional interaction between ephrinB and mGlu1 receptors, which likely involves adaptor or scaffolding proteins, might have an important role in the regulation of developmental plasticity.

Analysis of Variance↗
PubMed2005

Left ventricular myocardial mass determination by contrast enhanced colour Doppler compared with magnetic resonance imaging.

OBJECTIVE: To assess the feasibility of using contrast enhanced colour Doppler echocardiography to determine left ventricular (LV) mass and to compare its accuracy with LV mass obtained by magnetic resonance imaging (MRI). METHODS: Images were acquired in the short axis plane of the heart, derived from coronal and sagittal scout views and double oblique angulation. The LV mass was calculated by two methods: Simpson's rule and the area-length method. Levovist (Schering AG, Berlin, Germany) 2.5 g was given by slow intravenous bolus or infusion over about 45 seconds for contrast imaging. LV images were captured in the apical two chamber, four chamber, and three chamber views. Each contrast harmonic colour Doppler image was converted to a cavity-only image by simple image mathematics. RESULTS: 27 (77.1%) of the patients (mean (SD) age 66.2 (8.9) years) were men. There was a mean (SD) interval of 6.6 (8.6) days (range 0-27 days) between echocardiography and MRI. The mean (SD) LV mass determined by MRI Simpson's rule method was 171.0 (52.4) g (range 105.1-318.7 g). The mean LV mass (SD) determined by the echocardiographic Simpson's rule method was 178.2 (47.0) g (range 112.6-307.6 g). The mean (SD) MRI area-length LV mass was 187.3 (64.5) g (range 109.0-393.6 g). The linear regression correlation between LV mass determined by MRI Simpson's and echocardiographic Simpson's methods was excellent (y = 1.022x, R2 = 0.986) with a mean (SD) difference of 7.20 (20.9) g. The linear regression correlation between the MRI area-length LV mass and MRI Simpson's LV mass was excellent (y = 1.101x, R2 = 0.989) with a mean (SD) difference of 16.3 (22.3) g. CONCLUSIONS: LV mass may be obtained reliably by contrast enhanced colour Doppler and two dimensional echocardiography. The contrast Doppler method accurately determines LV mass with excellent agreement with the MRI technique.

Aged↗
PubMed2004

Nine years' experience of telecardiology in primary care.

The ITMS telecardiology network started in April 1995. Over nine years, about 7000 peripheral medical users (mainly general practitioners), who were experienced in using transtelephonic electrocardiography and who were spread throughout Italy, conducted teleconsultations with the Telecardiology Centre. A total of 106,942 patients were evaluated. Teleconsultation was carried out for non-cardiac symptoms or routine control for 30,444 patients (28%) and for symptoms suggestive of heart disease for 76,498 (72%). After teleconsultation, 61,908 patients (58%) were reported to have no heart disease, 27,947 patients (26%) had their drug dose adjusted and remained at home, 11,503 patients (11%) were sent to their cardiologist for further investigations and 5584 patients (5%) were urgently hospitalized. Among the hospitalized patients, the echocardiogram demonstrated an ST-elevation coronary syndrome in 1785 patients (32%), a non-ST-elevation coronary syndrome in 2236 (40%) and a life-threatening arrhythmia in 1354 (24%). Telecardiology improves the decision making of general practitioners, avoids unnecessary hospitalizations, reduces the time before treatment in cardiac emergencies, rationalizes health-care costs and promotes home care.

Adult↗
PubMed2002

Cor triatriatum sinistrum and persistent left superior vena cava: an original association.

Cor triatriatum sinistrum is a rare congenital heart disease usually diagnosed in symptomatic children. Symptoms depend on the degree of obstruction to pulmonary venous return with pulmonary hypertension and other associated abnormalities. Persistent left superior vena cava is quite a common congenital heart disease (about 0.5% in healthy populations). It should be suspected every time a dilated coronary sinus is detected at the echo examination. Transthoracic and transoesophageal examinations visualize the site and the size of the fibrous membrane as well as the degree of obstruction, and allow the evaluation of pulmonary pressures that are very important clues for prognosis and therapy. This case report describes the clinical signs and the diagnostic ultrasound findings evaluated in comparison with magnetic resonance imaging, a well-defined gold standard in heart disease of this uncommon congenital association.

Abnormalities, Multiple↗
PubMed2002

The role of telecardiology in supporting the decision-making process of general practitioners during the management of patients with suspected cardiac events.

We studied the role of telecardiology in reducing unnecessary hospital admissions of patients with suspected life-threatening cardiac events (CEs), evaluated by general practitioners (GPs). Over one month, 456 consecutive patients (mean age 65 years, SD 19) complaining of typical (10%) or atypical (42%) chest pain, palpitations (19%), dyspnoea (19%) or syncope (10%) were enrolled. Before teleconsultation, the GPs recorded their own opinion (based on clinical evaluation only) about the presence of a CE. Following transmission of the electrocardiogram (ECG), this opinion was compared with that of the cardiologist. In total there was agreement between the GP and cardiologist about the presence of a CE in 316 of the patients (69%) and disagreement in 140 patients (31%). This represents a specificity and sensitivity of the GPs' diagnosis of 76% and 47%, respectively. For 84 of 134 patients judged as having a CE by the GP, telecardiology avoided hospitalization; on the other hand, telecardiology identified a CE in 56 of 322 patients judged as not having a CE by the GP. Telecardiology is a useful tool with which to reduce unnecessary hospitalizations in patients with suspected life-threatening CEs.

Adult↗
PubMed2001

MR evaluation of coronary stents with navigator echo and breath-hold cine gradient-echo techniques.

The aim of this study was to evaluate coronary artery stents with MR. Thirty-eight patients underwent MR imaging 48.1 +/- 6.6 days (range 38-60 days) after placement of 47 coronary stents of 11 different types, using navigator echo (NE) and cine gradient-echo (GE) techniques. For both sequences the low signal artifact was used to localize the stent, whereas the flow-related high signal before and distal to the stent was considered as a patency sign. Exercise electrocardiographic test (EET) had been performed 1-7 days before MR. No adverse event with possible relation to the MR examination was observed. All the stents were recognized as signal void with GE, and all but one with NE. Of the 2 patients with positive EET, the first one, with a stent on the left anterior descending coronary artery, presented low signal distal to the stent at both MR sequences, suggesting dysfunction [60% stenosis at conventional coronary angiography (CCA)]; the second one, with two sequential stents on the right coronary artery, presented lack of signal distal to the stents at both MR sequences, suggesting occlusion (97% stenosis at CCA). For the 44 remaining stents in 36 patients with negative EET, MR high signal before and distal to the stent suggested patency at both sequences. MR seems to be a safe and promising technique for non-invasive evaluation of coronary stents.

Adult↗
PubMed2001

Long-term follow-up of right ventricular monomorphic extrasystoles.

OBJECTIVES: The purpose of this study was to verify in a long-term follow-up whether frequent monomorphic right ventricle extrasystoles may progress to arrhythmogenic right ventricular dysplasia (ARVD). BACKGROUND: Frequent monomorphic right ventricle extrasystoles are generally considered benign. However, in patients with this pattern, cardiac magnetic resonance (MR) has recently shown anatomical and functional abnormalities of the right ventricle. METHODS: Sixty-one patients who had been classified by noninvasive examinations as having frequent idiopathic right ventricle ectopy were contacted after 15 +/- 2 years (12 to 20) and submitted to clinical examination, electrocardiogram (ECG), Holter monitoring, stress test, signal averaged ECG, echocardiography and, in 11 patients, cardiac MR. The primary end point was to ascertain the presence of cases of sudden death or progression to ARVD. RESULTS: At the end of the follow-up, 55 patients were alive; six died, none of sudden death; eight stated to be well but refused further examinations. The 47 patients examined had normal ECG; in 24 patients (51%), extrasystoles were no longer present at Holter monitoring; late potentials were present in up to 15% of the patients; the right ventricle was normal at echocardiography. In 8 of 11 patients (73%), cardiac MR showed focal fatty replacement and other abnormalities of the right ventricle. CONCLUSIONS: In this long-term follow-up study, no patient died of sudden death nor developed ARVD; two-thirds of the patients were asymptomatic, and, in half of the patients, ectopy had disappeared. Focal fatty replacement in the right ventricle was present in most.

Adolescent↗
PubMed2001

The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells.

Group A streptococci (GAS) specifically attach to and internalize into human epithelial host cells. In some GAS isolates, fibronectin-binding proteins were identified as being responsible for these virulence traits. In the present study, the previously identified global negative regulator Nra was shown to control the binding of soluble fibronectin probably via regulation of protein F2 and/or SfbII expression in the serotype M49 strain 591. According to results from a conventional invasion assay based on the recovery of viable intracellular bacteria, the increased fibronectin binding did not affect bacterial adherence to HEp-2 epithelial cells, but was associated with a reduction in the internalization rates. However, when examined by confocal and electron microscopy techniques, the nra-mutant bacteria were shown to exhibit higher adherence and internalization rates than the corresponding wild type. The mutant bacteria escaped from the phagocytic vacuoles much faster, promoting consistent morphological changes which resulted in severe host cell damage. The apoptotic and lytic processes observed in nra-mutant infected host cells were correlated with an increased expression of the genes encoding superantigen SpeA, the cysteine protease SpeB, and streptolysin S in the nra-mutant bacteria. Adherence and internalization rates of a nra/speB-double mutant at wild-type levels indicated that the altered speB expression in the nra mutant contributed to the observed changes in both processes. The Nra-dependent effects on bacterial virulence were confined to infections carried out with stationary growth phase bacteria. In conclusion, the obtained results demonstrated that the global GAS regulator Nra modulates virulence genes, which are involved in host cell damage. Thus, by helping to achieve a critical balance of virulence factor expression that avoids the injury of target cells, Nra may facilitate GAS persistence in a safe intracellular niche.

Bacterial Adhesion↗
PubMed2000

Magnetic resonance imaging of athlete's heart: myocardial mass, left ventricular function, and cross-sectional area of the coronary arteries.

To evaluate left ventricular myocardial mass and function as well as ostial coronary artery cross-sectional area in endurance athletes, an athlete group of 12 highly trained rowers and a control group of 12 sedentary healthy subjects underwent MR examination. An ECG-gated breath-hold cine gradient-echo sequence was used to calculate myocardial mass, end-diastolic and end-systolic volumes, stroke volume, and cardiac output, all related to body surface area, as well as ejection fraction. A 3D fat-saturated ECG- and respiratory-triggered navigator echo sequence was used to evaluate coronary arteries: left main (LM), left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Cross-sectional area was calculated and divided for body surface area. Myocardial mass was found significantly larger in athlete group than in control group (p = 0.0078), the same being for end-diastolic volume (p = 0.0078), stroke volume (p = 0.0055), LM (p = 0.0066) and LAD (p = 0.0129). No significant difference was found for all the remaining parameters. Significant correlation with myocardial mass was found for LM (p < 0.001) and LAD (p = 0.0340), not for LCx and RCA. Magnetic resonance imaging is a useful tool in evaluating the myocardial hypertrophy and function of athlete's heart. Magnetic resonance angiography is a valuable noninvasive method to visualize the correlated cross-sectional area increase of the left coronary artery system.

Adult↗
PubMed2000

Adipose replacement and wall motion abnormalities in right ventricle arrhythmias: evaluation by MR imaging. Retrospective evaluation on 124 patients.

We reevaluated the magnetic resonance (MR) examinations of 38 healthy volunteers (control group, CG) and of 124 patients with RV arrhythmia with left bundle branch block (LBBB) morphology: 45 with episodes of RV sustained tachycardia and of polymorphic RV premature beats (RVST-PPB group); 36 with only RV outflow tract sustained or not sustained tachycardia (RVOTT group); 43 with RV monomorphic premature beats (RVMPB group). All the examinations were reevaluated in a blinded fashion for detecting myocardial adipose replacement (AR) and wall bulges or aneurysms. In RVST-PPB patients, no AR was observed in 9%; 1 RV region involvement, 0%; 2 regions, 4%; > or = 3 regions, 87%; left ventricle (LV), 15%. RVOTT patients: 28%, 53%, 14%, 5%, and 0% [corrected], respectively. RVMPB patients: 33%, 46%, 19%, 2%, and 0% [corrected], respectively. In CG, AR was observed in 11% (in RV outflow tract), RV bulges were detected in 75% [corrected] of RVST-PPB, 39% of RVOTT, and 14% of RVMPB patients, none of the CG; RV aneurysms in 33% of RVST-PPB patients, none of RVOTT patients, RVMBP patients, and CG. A significant difference among groups for RV and LV AR as well as RV bulges and aneurysms was found (p < 0.0001). In the direct comparisons, significant differences were found for: disease duration (RVST-PPB vs. RVMPB, p = 0.0396); RV AR (all the patients groups vs. CG, RVST-PPB vs. RVOTT or RVMPB, p < 0.0001); RV aneurysms (RVST-PPB vs. CG, RVST-PPB vs. RVOTT or RVMPB, p < 0.0002); bulges (all comparisons, p < 0.0174). AR is confirmed as a structural substrate in RV arrhythmias. Number and extension of MR abnormalities are correlated to different degrees of RV arrhythmias.

Adolescent↗
PubMed2000

Value of navigator echo magnetic resonance angiography in detecting occlusion/patency of arterial and venous, single and sequential coronary bypass grafts.

Aim of our work was to validate magnetic resonance angiography (MRA) in detecting occlusion/patency of coronary artery bypass grafts. Twenty patients with previous history of bypass surgery and recurrent episodes of chest pain were enrolled. Two patients could not be studied (claustrophobia, erratic breathing). Thus, 18 patients with 51 bypasses were examined using a navigator echo sequence: 21 arterial grafts (six sequential) and 30 saphenous vein grafts (five sequential). All patients had undergone contrast conventional angiography 3-15 days before MRA. The magnetic resonance (MR) data set was analyzed by two independent readers blinded to the results of conventional angiography (occlusion of 12 of 51 grafts). At magnetic resonance, two bypasses of the posterior descending artery, patent at conventional angiography, could not be visualized because of imaging slab malpositioning. Interobserver concordance was 96% (47/49). Magnetic resonance and conventional angiography provided identical answers in 47 out of 49 (96%) of the examined grafts. Eleven out of 12 occluded grafts and 36 out of 37 patent grafts were correctly identified with MR. As far as occlusion is concerned, the sensitivity of MR was 91%, the specificity 97%. To summarize, a 30 min outpatient MR examination is highly reliable in determining occlusion/patency of arterial and venous, single and sequential bypasses.

Coronary Angiography↗
PubMed2000

Two distinct pathways for the invasion of Streptococcus pyogenes in non-phagocytic cells.

Adherence to and invasion of epithelial cells represent important pathogenic mechanisms of Streptococcus pyogenes. A fibronectin-binding surface protein of S. pyogenes, Sfbl protein, has been implicated in both adherence and invasion processes. Invasion of Sfbl-containing strains has been suspected to be responsible for the failure of antibiotics treatment to eradicate S. pyogenes. In this study, we tested the adherence and invasion properties of two well-characterized clinical isolates: A40, which expresses Sfbl; and A8, which is Sfbl negative and is unable to bind fibronectin. In strain A40, Sfbl was the main factor required for attachment and invasion by using fibronectin as a bridging molecule and the alpha5beta1 integrin as cellular receptor. The uptake process was characterized by the generation of large membrane invaginations at the bacteria-cell interface without evidence of actin recruitment or cellular injury. A40 cells were located in phagosomes and, only 24 h after infection, a consistent part of the bacterial population reached the cytoplasm. In contrast, uptake of strain A8 required major rearrangements of cytoskeletal proteins underneath attached bacteria. In A8, a proteinaceous moiety was involved, which does not interact with alpha5beta1 or need any known bridging molecule. Bacterial attachment stimulated elongation and massive recruitment of neighbouring microvilli, which fused to surround streptococcal chains. They led to the generation of large pseudopod-like structures, which engulfed bacteria that were rapidly released and replicated in the cytoplasm. The identification of two completely different uptake pathways reported here provided further evidence regarding the diversity of S. pyogenes isolates and might contribute towards understanding the pathogenesis and persistence of S. pyogenes.

Actins↗
PubMed2000

Co-operative binding of human fibronectin to Sfbl protein triggers streptococcal invasion into respiratory epithelial cells.

Streptococcal fibronectin binding protein I (SfbI) mediates adherence to and invasion of Streptococcus pyogenes into human epithelial cells. In this study, we analysed the binding activity of distinct domains of SfbI protein towards its ligand, the extracellular matrix component fibronectin, as well as the biological implication of the binding events during the infection process. By using purified recombinant SfbI derivatives as well as in vivo expressed SfbI domains on the surface of heterologous organism Streptococcus gordonii, we were able to dissociate the two major streptococcal target domains on the human fibronectin molecule. The SfbI repeat region exclusively bound to the 30 kDa N-terminal fragment of fibronectin, whereas the SfbI spacer region exclusively bound to the 45 kDa collagen-binding fragment of fibronectin. In the case of native surface-expressed SfbI protein, an induced fit mode of bacteria-fibronectin interaction was identified. We demonstrate that binding of the 30 kDa fibronectin fragment to the repeat region of SfbI protein co-operatively activates the adjacent SfbI spacer domain to bind the 45 kDa fibronectin fragment. The biological consequence arising from this novel mode of fibronectin targeting was analysed in eukaryotic cell invasion assays. The repeat region of SfbI protein is mediating adherence and constitutes a prerequisite for subsequent invasion, whereas the SfbI spacer domain efficiently triggers the invasion process of streptococci into the eukaryotic cell. Thus, we were able to dissect bacterial adhesion from invasion by manipulating one protein. SfbI protein therefore represents a highly evolved prokaryotic molecule that exploits the host factor fibronectin not only for extracellular targeting but also for its subsequent activation that leads to efficient cellular invasion.

Adhesins, Bacterial↗
PubMed2000

Three-dimensional, navigator-echo MR coronary angiography in detecting stenoses of the major epicardial vessels, with conventional coronary angiography as the standard of reference.

PURPOSE: To test three-dimensional (3D), navigator-echo magnetic resonance (MR) coronary angiography in detecting stenoses of the coronary arteries. MATERIALS AND METHODS: Forty-two patients (age range, 50-79 years) underwent MR coronary angiography (1.5 T). A navigator-echo sequence was used. Two or three 15% overlapped transverse slabs were acquired. Data were analyzed by readers blinded to conventional coronary angiographic results. On conventional coronary angiograms, coronary arterial stenoses of 50% or greater narrowing were considered significant. On MR coronary angiograms, the major coronary vessels were subdivided into proximal (within 5 cm) and distal (beyond 5 cm) segments, except for the left main vessel. Stenoses of 50% or greater were identified on reformatted multiplanar MR coronary angiograms. RESULTS: Three MR coronary angiographic examinations were aborted because of patient claustrophobia; 39 of 39 left main, 117 of 117 proximal, and 78 of 117 distal segments were visualized. MR coronary angiography showed a sensitivity of 82% (95% CI: 73%, 91%) and a specificity of 89% (95% CI: 85%, 94%) in overall stenoses identification, of 90% (95% CI: 81%, 99%) and 90% (95% CI: 83%, 96%) for proximal segments, and of 68% (95% CI: 50%, 86%) and 81% (95% CI: 71%, 92%) for distal segments, respectively. CONCLUSION: Navigator-echo, 3D MR coronary angiography is a promising sequence for assessing coronary arterial stenoses, but further improvements are required for distal segments.

Aged↗
PubMed2000

Coronary aneurysms and stenosis detected with magnetic resonance coronary angiography in a patient with Kawasaki disease.

Coronary artery abnormalities in Kawasaki syndrome develop in about 15-25% of young patients, mostly as aneurysms. In the long-term evolution of coronary artery disease thrombotic occlusion of aneurysms, premature atherosclerosis, and stenosis, are observed. Magnetic resonance is an emerging modality in the angiographic assessment of coronary arteries. The authors report a case of coronary artery aneurysms and stenosis in a 26-year-old patient with Kawasaki disease detected by magnetic resonance coronary angiography and confirmed by conventional coronary angiography.

Adult↗
PubMed1999

Fc-mediated nonspecific binding between fibronectin-binding protein I of Streptococcus pyogenes and human immunoglobulins.

Fibronectin-binding protein I (SfbI) from Streptococcus pyogenes plays a key role in bacterial adhesion to, and invasion of, eukaryotic cells. In addition, SfbI exhibits a considerable potential as mucosal adjuvant and can trigger polyclonal activation of B cells. Here, we report that SfbI is also capable of binding human IgG in a nonimmune fashion. SfbI was reactive with IgG1, IgG2, IgG3, and IgG4 isotypes (type IIo IgG-binding profile). The affinity constant (Kd) of the SfbI-IgG interaction was in the range of 1-2 x 10(-5) M. Further studies demonstrated that the SfbI binding was mediated by the Fc component of the IgG molecule. Experiments performed using purified recombinant proteins spanning different domains of SfbI showed that the IgG-binding activity was restricted to the fibronectin-binding domains, and in particular to the fibronectin-binding repeats. Finally, the presence of recombinant SfbI resulted in an impairment of both phagocytosis of IgG-coated RBCs and Ab-dependent cell cytotoxicity by macrophages. These results demonstrated for the first time that, in addition to its major role during the colonization process, SfbI may also favor bacterial immune evasion after the onset of the infection by interfering with host clearance mechanisms.

Adhesins, Bacterial↗
PubMed1999

Streptococcal invasion.

The genus Streptococcus consists of large number of species many of which are pathogenic to humans and animals. Although streptococci have long been considered as extracellular pathogens, they are capable of causing serious invasive infections such as necrotizing fasciitis and meningitis. Streptococcal invasion, therefore, has been a focus of many studies in recent years. Streptococci are efficiently internalized by nonprofessional phagocytes and the current research interest has shifted to determine the role of this invasion in the natural infection process. Moreover, characterization of bacterial and eukaryotic components involved in the uptake process might be useful in developing new strategies for combating streptococcal infections.

Adhesins, Bacterial↗