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Biomedical subjects

M Fabbri

Publications and source records attributed to M Fabbri.

84 records · Page 5Linked to original sources
PubMedDate not supplied

Biochemical characterization by two-dimensional electrophoresis of lymphocyte antigens involved in cell-to-cell or cell-to-matrix adhesion.

We have exemplified three cases of application of two-dimensional (2-D) electrophoresis to the characterization of lymphocyte membrane antigens. We could show that the proteins recognized by two monoclonal antibodies, LAK1 and LAK2, on the surface of large granular cells mediating natural- and lymphokine-activated killing are distinct molecules. LAK1 is expressed without any structural modification, even on the surface of endothelial cells. Another membrane antigen, recognized by the monoclonal antibody FB12, was shown to have the overall structure of the integrins of the very late activation (VLA) class, being composed of an alpha and of a beta subunit. The latter corresponded to the beta 1 type as already characterized for other VLAs, whereas the alpha chain was different from alpha 1 through alpha 6. The 2-D protocol using immobilized pH gradients for the first dimension allows reliable assessment of the identity of individual components because of the reproducibility of the absolute coordinates for spot position.

Antibodies, Monoclonal↗
PubMedDate not supplied

Tumor infiltrating lymphocytes and continuous infusion interleukin-2 after metastasectomy in 61 patients with melanoma, colorectal and renal carcinoma.

AIMS AND BACKGROUND: Adoptive immunotherapy with tumor infiltrating lymphocyte (TIL) reinfusion plus continuous interleukin-2 (IL-2) infusion could represent an innovative way of treating immunogenic tumors. This study therefore recruited melanoma, colorectal and renal carcinoma patients whose metastases had been surgically removed. STUDY DESIGN: The treatment was initially given to 22 patients with advanced disease and more recently to 39 disease-free (DF) patients after radical metastasectomy. The latter group was selected in view of a theoretically better lymphocyte/tumor cell ratio and with the aim to improve disease-free and overall survival (DFS-OS) in very high risk patients. The starting IL-2 dose was 12 MIU/day (West's schedule); doses were modulated on the bases of toxicity parameters. Even though patients received different total amounts of IL-2, all of them completed the treatment. RESULTS: The treatment was offered to 22 advanced-stage cancer patients (12 melanomas, 9 colorectal carcinomas, 1 kidney carcinoma). Few and short stabilizations were observed with a median survival of 12 months (range, 3-29). Subsequently, another 39 patients were treated in an adjuvant setting after radical metastasectomy (18 melanomas, 19 colorectal carcinomas, 2 kidney cancers). Eleven out of 17 DF melanoma patients (64.7%) are still free of disease after a median of 37+ months (range, 5+ - 69+). In the group of DF colorectal cancer patients eight (44.4%) are still DF after a median of 21+ months (range, 7+ - 67+ months). One of the two patients with kidney cancer is still DF after 28+ months. Two patients (1 melanoma and 1 colorectal cancer) had just been treated and were therefore not evaluable. Severe toxicity occurred in three cases but was rapidly resolved. There was a great diversity in IL-2 doses administered; comparison of the total IL-2 dose administered between the patients who are still DF and those who progressed revealed no difference between the two groups of colorectal cancer patients, whereas melanoma patients who progressed received an average IL-2 dose of 6.5 MIU/day versus 15.8 MIU/day in DF patients. No differences were observed in any of the groups between the number of TILs reinfused and clinical response. CONCLUSIONS: The study is still ongoing; it has been decided to focus on DF melanoma patients after radical metastasectomy, for whom the data seem to be encouraging. Further endpoints of the study are the role of IL-2 dosage in the adjuvant setting, and the possibility to make correlations between biological parameters and clinical results.

Adult↗
PubMedDate not supplied

Noninvasive prediction of restenosis after coronary angioplasty: a head to head comparison among exercise ECG, dipyridamole and exercise thallium scintigraphy.

Restenosis remains the main limitation of percutaneous transluminal coronary angioplasty (PTCA). Since it seems likely that restenosis not severe enough to induce ischemia may be better detected with pharmacological testing than with exercise, we investigated whether dipyridamole thallium scintigraphy is better than exercise-electrocardiogram and exercise-thallium in predicting restenosis after PTCA. Noninvasive tests and re-angiography were performed in 61 consecutive patients, 5-6 months after successful single vessel PTCA. Detection of vessel stenosis greater than or equal to 50% was used as angiographic criteria for restenosis. Exercise-induced angina, ST segment depression greater than or equal to 1 mm at exercise-electrocardiogram and reversible perfusion defects in the area supplied by the dilated vessel, during either dipyridamole and exercise-thallium, were considered noninvasive abnormal responses. The overall restenosis rate was 41% (25/61). Angina was the most specific (97%) of all criteria for restenosis, but also one of the least sensitive (40%), slightly better than exercise-ECG (24%). Exercise-thallium had lower sensitivity (72% vs 88%, p less than 0.05) and negative predictive value (82% vs 91%, p less than 0.05) than dipyridamole-thallium. In patients positive at both exercise-thallium and dipyridamole-thallium testing, mean stenosis at follow-up was more severe (73 +/- 23%) than in patients with positive dipyridamole-thallium and negative exercise-thallium (55 +/- 26%) results, but the difference did not reach statistically significant levels. For these reasons, dipyridamole-thallium seems to be an acceptable alternative to exercise thallium to follow patients after initially successful PTCA.

Aged↗
PubMedDate not supplied

Membrane gangliosides and immuno-mediated cytolysis in drug sensitive and treatment-induced multidrug resistant human ovarian cancer cells.

The pattern of cytoplasmic membrane gangliosides and two cellular features which have been reported to be related to the expression of different membrane gangliosides, namely adhesion to solid substrates and susceptibility to the lytic activity of immune effector cells, have been investigated in drug sensitive A2780 human ovarian cancer cells and in two treatment-induced multidrug resistant sublines (A2780-DX1 and A2780-DX3). The total membrane gangliosides content of A2780 sensitive cells was comparable to that of the two multidrug resistant (MDR) sublines, but the acquisition of the MDR phenotype was characterized by an increased expression of the polysialylated gangliosides (particularly the disialoganglioside GDIa) and decreased expression of the monosialoganglioside GM2. The kinetics of cellular adhesion (both to plastic culture dishes and to extracellular matrix coated dishes) were similar in the three cell lines, indicating that the gangliosides profile seems not to be relevant for cell adhesivity to the above mentioned substrates. When human peripheral blood lymphocytes in toto (PBL) and two lymphokine activated (LAK) T cell subpopulations (CD3+4-8- and CD3-16+) were used as effector cells against A2780 (sensitive) and A2780-DX3 (highly resistant) cells, cytolysis of target cells was more efficient against the A2780-DX3 subline, suggesting a possible role of the ganglioside GD1a as a target structure for LAK immunotherapy.

Antineoplastic Agents↗
PubMedDate not supplied

Efficacy and tolerability of nedocromil sodium versus placebo in chronic reversible obstructive airways disease.

In this 8-week, double-blind, comparative trial of nedocromil sodium (4 mg q.i.d.) versus placebo in 42 patients with chronic reversible obstructive airways disease, there was a trend in favor of nedocromil sodium compared to placebo in parameters assessed by patients (nocturnal symptom scores, evening PEFR values) and those assessed by clinicians (asthma severity scores) compared with baseline values. There was a statistically significant difference (p < 0.05) in favor of nedocromil sodium in the inhaled bronchodilator requirements in the last 2 weeks of treatment. Both patients' and clinicians' evaluation of the overall efficacy of treatment was significant in favor of nedocromil sodium (p < 0.01 and p < 0.05, respectively). The treatments were well tolerated by the majority of patients. From these data, it can be concluded that nedocromil sodium (4 mg q.i.d.) is of value in the preventive treatment of chronic reversible obstructive airways disease.

Adult↗
PubMedDate not supplied

[The assessment of the severity of pulmonary edema by computed tomography. A comparison between high-resolution computed tomography, objective evaluation with density masks and functional tests].

The results of high-resolution computed tomography (HRCT) were correlated with those of pulmonary function tests, chest films and CT expiratory density mask values in the evaluation of pulmonary emphysema in 33 symptomatic subjects. Emphysema was quantitated with both subjective and objective measurements. Conventional chest films were useful to diagnose severe emphysema but its actual extent was more reliably evaluated with CT scoring systems. HRCT and density mask correlated well with function tests, but the former method exhibited stronger correlation with carbon monoxide diffusion capacity. The opposite was true for hyperinflation and expiratory obstruction variables. Subjective CT estimates, which are quick and easy to perform, were seen to correspond more specifically to the pathophysiologic derangement and should therefore be used to evaluate the anatomic extent of disease. The functional severity of emphysema correlated only with the overall extent of disease and not with its regional distribution in the upper or lower lungs. Finally, in 4 cases (12.1%) with low CT scores, FEV1 was reduced but diffusion capacity values were normal. In one of these patients HRCT showed signs of bronchiolitis. In fact, small airway disease might be a more critical factor in determining functional impairment than the actual anatomical emphysema.

Adult↗