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Biomedical subjects

G Antonelli

Publications and source records attributed to G Antonelli.

At least 127 records · Page 7Linked to original sources

Inhibition of contact sensitivity to oxazolone by the calmodulin inhibitor trifluoroperazine.

Topical application of trifluoroperazine (TFP), a calmodulin inhibitor, on the skin of CBA mice previously immunized with 2-phenyl-4-ethoximethylene-oxazolone (oxazolone) blocks the expression phase of contact sensitivity. More detailed analysis of the TFP-mediated inhibition of contact sensitivity shows that TFP significantly suppresses the passive transfer of contact sensitivity when added in vitro to oxazolone-immune cells at a molar concentration of 10(-4) -10(-5). Furthermore, the DNA synthesis of draining lymph node cells from immune mice challenged with oxazolone was suppressed when cultured in the presence of TFP. The exposure of spleen and lymph node cells from immune animals to recombinant IL-2 fails to modify the TFP-mediated inhibition of passive transfer and cell proliferation. The TFP topical application opens the possibility to use this compound in the treatment of delayed hypersensitivity-caused skin disorders.

Administration, Topical↗

Pharmacokinetics of recombinant interferon-alpha 2 following intralesional administration in malignant glioma patients.

Pharmacokinetics of recombinant interferon-alpha 2 (rIFN-alpha 2) following intralesional administration into patients with malignant gliomas was investigated. A dose of 5 X 10(6) IU of rIFN-alpha 2 was injected locally postoperatively for 2 weeks each day, and the same dose was then given once a week for 10 additional weeks. During the daily and weekly administration, the IFN was consistently present in the fluid of the postsurgical cavity. Not until 5 weeks after the end of the IFN administration was the IFN undetectable. The decay of IFN injected was minimal.

Adult↗

Influence of monoclonal antibodies against HLA class I and class II antigen on interferon-gamma and -alpha induction.

The effects of several monoclonal antibodies (MAbs) directed against different epitopes of HLA class I and class II antigens on interferon (IFN)-gamma and IFN-alpha production were studied. The results indicate that: these MAbs have a marked inhibitory effect on the production of IFN-gamma induced by alloantigens and microbial antigens; they influence only to a lesser extent staphylococcal enterotoxin B (SEB)- and phytohemagglutinin (PHA)-induced IFN-gamma production; such effects parallel inhibition of lymphoproliferation except for PHA-induced blastogenesis, which is not affected; on the other hand, these MAbs have no effect on the production of IFN-alpha induced by lipopolysaccharide (LPS) or viruses.

Adult↗

Antigen presentation by specifically sensitized macrophages in interferon-gamma induction.

Antigenic stimulation of specifically sensitized T lymphocytes to interferon-gamma (IFN-gamma) production requires the presence of macrophages. This study examines the ability of peritoneal macrophages from immunized mice to present the antigen to antigen-specific lymphocytes. Such cells presented purified protein derivative (PPD) of tuberculin at concentrations as low as 0.1 micrograms/ml to sensitized T lymphocytes. In contrast, peritoneal macrophages from unimmunized animals required 1,000-fold higher concentrations of antigen to stimulate the same lymphocytes. The presentation of low concentrations of antigen by macrophage from immunized animals was significantly blocked by anti-immunoglobulin antibody, indicating that the surface immunoglobulin receptors were critically involved in this phenomenon. These results suggest that surface immunoglobulins serve to focus antigens onto specific macrophages and that such cells are highly efficient at presenting linked antigenic determinants to T cells. The implication of these findings for the mechanism of IFN-gamma induction are discussed.

Animals↗

Hydatid cyst of the interventricular septum causing obstruction of the right ventricular outflow tract: cross-sectional echocardiographic, angiographic and pathological findings.

Cardiac echinococcal cysts rarely involve the interventricular septum; when they do, they cause symptoms mainly related to the compression of the atrio-ventricular conduction pathways. Mild obstruction of the right ventricular outflow tract has also been described in some cases. In the case reported here, an unusual large hydatid cyst located in the interventricular septum produced a marked, symptomatic obstruction of the right ventricular outflow tract (more than 100 mmHg gradient). Surgical resection of the cyst was complicated by a 'stone heart' syndrome, probably because of a severely affected right ventricle. Cross-sectional echocardiography gave the exact site and aetiology of the mass. On the basis of these non-invasive findings, early surgery should be performed on asymptomatic patients to reduce the risk of life-threatening evolutions.

Adult↗

An influenza virus inhibitor that acts late in the replication cycle.

An inhibitor which is active against influenza A virus was found in Neuramide, a complex tissue extract that is used as an anti-herpes zoster virus treatment. Kinetic studies showed that significant inhibition of virus production occurred when the inhibitor was added to infected cultures up to 5 h after virus penetration. Molecular sieving fractionation showed that the antiviral activity was contained in a low-molecular-weight fraction (molecular weight, less than 1,000).

Animals↗

Generation of a soluble IFN-gamma inducer by oxidation of galactose residues on macrophages.

Depletion of macrophages from human peripheral blood mononuclear cells (PBMC) caused a marked decrease in galactose oxidase and sodium periodate, but not a calcium ionophore, stimulated Interferon-gamma (IFN-gamma) production. Reconstitution of such depleted cultures with galactose oxidase treated macrophages, but not lymphocytes, restored IFN-gamma levels to those of control nonfractionated PBMC. Thus, galactose oxidase seemed to act on macrophages which in turn stimulated lymphocyte production of IFN-gamma. Unlike human cells which have terminal galactose residues on glycoproteins, murine cell glycoproteins terminate their oligosaccharide component in the order N-acetyl-neuraminic acid followed by D-galactose, N-acetyl-glucosamine, and glycoprotein. Galactose oxidase or sodium periodate only activated murine macrophages to stimulate lymphocyte IFN-gamma production after exposing D-galactose residues by the removal of the terminal N-acetyl-neuraminic acid residues with neuraminidase. Removal of such exposed terminal galactose residues with beta-galactosidase inhibited the effect of galactose oxidase on murine macrophages. Taken together, these results strongly suggest that oxidation of terminal galactose residues on macrophages is the initial site of action of galactose oxidase and sodium periodate. Studies with Boyden chambers have shown that galactose oxidase-treated macrophages released a soluble factor which stimulates lymphocyte production of IFN-gamma. Based on these findings, it appears that the oxidation of terminal galactose residues on the surface of macrophages leads to the induction and transmission of a soluble signal for lymphocyte production of IFN-gamma.

Animals↗

Membrane events leading to interferon-gamma induction by antigens.

Mitogenic induction of interferon-gamma in human peripheral blood mononuclear cells (PBMC) is prevented by enzymatic cleavage of galactose residues on the cell membrane, and by calcium depletion, suggesting that oxidation of galactose on the membrane glycoproteins and activation of a calcium flux across the membrane are critical events for interferon-gamma induction in nonspecifically stimulated human PBMC. The same experimental design has been applied to human PBMC cultures enriched of specifically sensitized lymphocytes and stimulated with the respective antigens. The results of these experiments show that also antigenic induction of interferon-gamma by purified protein derivative, tetanus toxoid, and MLR requires integrity of galactose residues and calcium intake suggesting that alteration of membrane-bound galactose and activation of a calcium flow are critical triggering events for both specific and nonspecific lymphocyte activation.

Adult↗

Induction of alpha interferon by membrane interaction between viral surface and peripheral blood mononuclear cells.

Cells infected with viruses and fixed when viral antigens appeared at the cell membrane induced much higher alpha interferon (IFN-alpha) levels in human peripheral blood mononuclear cells (PBMC) than free virions. Relatively few inducer cells were sufficient for triggering IFN production. Optimal IFN yields depended on inducer/producer cell ratio. The response was peculiar to PBMC as it was not found in other cells in which IFN can normally be induced by free virions. IFN inducing activity was also exerted by live virus-infected PBMC, showing that this type of induction may have physiological importance. These findings confirm that viral induction of IFN-alpha is activated by some interaction between viral components presented at the cell surface and PBMC membrane. Thus induction of IFN by circulating cells infected by viruses and presenting viral antigens at the surface may be an efficient host defense mechanism. Since IFN yields close to 10(6) international units per milliliter are obtained, this system has potential for large scale production of native IFN-alpha.

Animals↗

[Spontaneous echocontrastography. Analysis of 50 cases, review of the literature and a proposal for its classification].

Spontaneous echocontrastographic effect (SEE) is sometimes detected in cardiac chambers. In order to propose a classification of the phenomenon we reviewed our series of 50 patients with SEE. We detected three type of SEE: type I, II, III. Type I was characterized by the presence of low amplitude echoes with slow and irregular motion in a cardiac chamber, in some cases the cloud of echoes had not defined borders (type IA), in other cases the cloud had well defined borders and was attached to a mural thrombus (type IB). Type II was characterized by the presence of echoes moving quickly across the mitral valve toward the left ventricle apex. Lastly, type III was characterized by the presence of microbubbles slowly and chaotically moving in right cardiac chambers. Type I SEE was detected only in patients with clinical conditions (mitral stenosis, congestive cardiomyopathies) characterized by slow intracardiac flow; type II was detected in 3 patients with mitral prosthesis, in 3 with constrictive pericarditis and 1 with severe aortic insufficiency. Lastly, type III was detected in 5 patients with tricuspid insufficiency.

Adolescent↗

Detection of atrial septal defect by right sternal border echocardiography.

The atrial septum can be visualized by right sternal border 2-dimensional echocardiography (2-D echo). To evaluate the usefulness of this approach in the evaluation of atrial septal defect (ASD), 50 patients who underwent cardiac catheterization were studied by 2-D echo. Twenty-one patients (Group A) had ASD (3 ostium primum, 18 ostium secundum) and 29 (Group B) had mitral valve disease and an intact atrial septum. Subcostal and right sternal border approaches were used to visualize the atrial septum. Both approaches identified the 3 cases of ostium primum ASD; secundum ASD was identified using the subcostal approach in 11 patients and using the right sternal border approach in 13. In 15 patients the ASD was imaged at least by 1 of the 2 approaches. Two-dimensional contrast echocardiography showed a positive or negative contrast effect in 13 of 18 cases (12 with standard approaches, 11 with right sternal border approach). In all patients in Group B, the right sternal border approach showed an intact atrial septum. Thus, the right sternal border approach is a useful approach that increases the sensitivity of 2-D echo in the diagnosis of ASD.

Adolescent↗

Two-dimensional echocardiographic recognition of complications of cardiac invasive procedures.

Two-dimensional echocardiography allowed prompt recognition of a major complication of a cardiac invasive procedure in 6 patients. In 5 cases, a preinvasive echocardiographic study was available for comparison. In 1 patient with perforation of the ventricular septum by a temporary pacemaker, the catheter was visualized as it passed through the ventricular septum, with the tip located against the left ventricular posterolateral wall. In another patient, the intimal flap caused by aortic dissection after left-sided heart catheterization was clearly visualized. In 2 patients with hemopericardium secondary to cardiac perforation during right-sided cardiac catheterization, 2-dimensional echocardiography revealed pericardial effusion not noted in studies performed before the invasive procedure. Two patients in whom hemopericardium occurred from injury by the pericardiocentesis needle also were studied by 2-dimensional echocardiography. Postpericardiocentesis images revealed new intrapericardial abnormalities (a thrombus-like mass and fibrinous strands) not present in the echocardiographic studies performed before pericardiocentesis. Real-time 2-dimensional echocardiography appears to be a good tool in the recognition of the emergencies secondary to cardiac invasive procedures.

Adult↗