Ascending aorta aneurysm in an asymptomatic child with cystic medial necrosis and familiar history of aortic disease.
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Biomedical subjects
Publications and source records attributed to G Salamone.
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Physical and functional association between the beta2-integrin Mac-1 (CD11b/CD18) and receptors of immunoglobulin G (IgG) (FcgammaRs) has been previously reported. In this study, we examined the modulation of Mac-1 expression by IgG in different leucocyte populations. Our data show that human monocytes, but not neutrophils, macrophages, dendritic or natural killer cells, downregulate the expression of Mac-1 after overnight exposure to surface-bound IgG. This effect, which requires at least 6 h of incubation, is not associated with a general downmodulation of membrane antigens, and is selectively induced by immobilized IgG (iIgG), as the stimulation of monocytes with N-formyl-methionyl-leucyl-phenylalanine, lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha) or soluble IgG did not modify the Mac-1 expression after 18 h in culture. The loss of Mac-1 was completely prevented by blocking antibodies (Abs) directed to FcgammaRII (CD32) or CD18. On the other hand, the serine protease inhibitor, phenyl methyl sulphonyl fluoride, but not inhibitors of cysteine proteases or neutral endopeptidases, partially prevented the downregulation of Mac-1 by iIgG. Monocytes cultured overnight on iIgG exhibited a dramatic decrease in their capacity to ingest zymosan particles that could be attributed to the reduced expression of Mac-1. However, there was no inhibition of TNF-alpha production induced by zymosan, suggesting that Mac-1-dependent responses require different levels of its expression to be fully activated.
We examined the ability of TNF-alpha to modulate human neutrophil apoptosis. Neutrophils cultured with TNF-alpha alone undergo a low but significant increase in the number of apoptotic cells. More interestingly, when neutrophils were pretreated with TNF-alpha for 1-2 min at 37 degrees C and then were exposed to a variety of agents such as immobilized IgG, IgG-coated erythrocytes, complement-treated erythrocytes, zymosan, PMA, zymosan-activated serum, fMLP, Escherichia coli, and GM-CSF for 3 h at 37 degrees C, a marked stimulation of apoptosis was observed. Similar results were obtained in neutrophils pretreated with TNF-alpha for 30 min, 1 h, 3 h, and 18 h. Dose-dependent studies showed that TNF-alpha enhances neutrophil apoptosis at concentrations ranging from 1 to 100 ng/ml. In contrast to the observations made in neutrophils pretreated with TNF-alpha, there was no stimulation of apoptosis when TNF-alpha was added to neutrophils previously activated by conventional agonists. Experiments performed to establish the mechanism through which TNF-alpha promotes neutrophil apoptosis showed that neither reactive oxygen intermediates nor the Fas/Fas ligand system appear to be involved. Our results suggest that TNF-alpha plays a critical role in the control of neutrophil survival by virtue of its ability to induce an apoptotic death program which could be triggered by a variety of conventional agonists.
Malignant B cells from chronic lymphocytic leukemia (B-CLL) patients have a long survival in vivo, although, in culture, they spontaneously die by apoptosis. Here, we analyzed the capacity of accessory leukocytes to modulate apoptosis of B-CLL cells in vitro. To this end, we performed long-term cultures using total mononuclear cells (TMC) from B-CLL patients and TMC depleted from monocytes, NK cells and T lymphocytes (B-CLL cells). In all the patients studied (n = 25) the presence of accessory leukocytes markedly prolonged the survival of B-CLL cells. The anti-apoptotic effect was exerted by monocytes and, to a lesser degree, NK cells, partially through the release of soluble factors. Indeed, accessory leukocytes separated from leukemic cells by semipermeable membranes were still able to prolong B-CLL cell survival. By flow cytometric analysis we found that the protective effect of non-malignant cells was associated with delayed down-regulation of Bcl-2 expression on leukemic cells. By contrast, the expression of Fas and Fas ligand proteins was unchanged in most samples. Our findings suggest that monocytes and NK cells, by delaying leukemic cell apoptosis, may play a role in B-CLL cell accumulation in vivo.
The interaction of immunoglobulin G (IgG) antibodies with FcgammaR constitutes a critical mechanism through which IgG antibody effector functions are mediated. In the current work we have examined whether human neutrophil FcgammaR exhibit pH dependence in their association with IgG. Binding assays were performed in culture medium adjusted to different pH values. It was found that the binding of either heat-aggregated human IgG (AIgG), soluble immune complexes (sIC) or IgG-coated erythrocytes (IgG-E) was markedly higher at pH 6.5 than at pH 7.3. This effect was not observed when saturation of FcgammaR was achieved, suggesting that acidic pH increases the avidity of FcgammaR for IC without modifying the total binding capacity. Similar results were observed for the binding of AIgG to either monocytes, natural killer (NK) or K562 cells, suggesting that acidic pH increases the avidity of both, FcgammaRII and FcgammaRIII. Additional experiments were performed to analyse whether the binding of IgG to FcgammaRI also showed pH dependence. To this aim, we employed interferon-gamma-treated human neutrophils and mouse inflammatory macrophages, previously incubated with blocking antibodies directed to FcgammaRII and FcgammaRIII. Acidic pH did not enhance the binding of AIgG nor monomeric IgG under these experimental conditions. Further studies are required to determine whether the enhancement of FcgammaR avidity for IC could be attributed to titration of histidine(s) residues on the Fc fragment of IgG.
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Between December 1975 and February 1984 five patients with Transposition of the great arteries and large ventricular septal defect underwent repair by arterial switching with reimplantation of the coronary arteries. They ranged in age from 2 to 28 months and weighted between 3.2 and 10 kg. The oldest patient had underwent banding of the pulmonary artery together with a Blalock-Hanlon septectomy at 6 months of age. Direct reconstruction of the "new" pulmonary artery was achieved in 4 patients. The first of these patients operated upon on December 1975 died of acute left ventricular ischemia due to compression of the main left coronary artery caused by the newly reconstructed pulmonary artery. This death appears to be technically avoidable by using the method recently reported by Lecompte. One patient who was in good hemodynamic status died of mediastinitis 2 months after the repair. At necropsy the repair was found intact and the woven dacron conduit used to reestablish the continuity to pulmonary artery was found grossly infected. The remaining three patients continue to be asymptomatic 48, 40 and two months respectively after repair. Our small experience supports the anatomic correction as the procedure of choice for the surgical treatment of most of the patients with Transposition of the great arteries and large ventricular septal defect.
AIM OF THE STUDY: Evaluation of total thyroidectomy, subtotal thyroidectomy and lobectomy in the management of multinodular non-toxic goitre. MATERIALS AND METHODS: 225 patients: 101 total thyroidectomies, 64 sub-total thyroidectomies, 29 lobo-hystmectomies. Hemorrages, recurrent nerve palsies, post-operatory hypocalcemias, clinical and ultrasonographic relapses, undesired effects of ormonal therapy and hypothyroidism after partial resection (considered risk factor for recurrence) have been pointed out. RESULTS: All three procedures showed a low incidence of recurrent nerve palsy; lobectomy didn't show post-operatory hypocalcemia, that appeared respectively in 26.6% and 23% after sub-total and total thyroidectomy. Recurrence's percentage in patients followed-up, was 18.2% after lobectomy and 12.2% after sub-total thyroidectomy, but in that group we observed 46.9% of hypothyroidism (vs. 9.1% after lobectomy) and 8.6% of undesired effects of therapy. Reoperations showed inferior laringeal palsy and post-operatory hypocalcemia significantly more elevated. DISCUSSION: Compared to lobectomy, total thyroidectomy showed higher risk of hypoparathyroidism; compared to subtotal thyroidectomy, it showed on all occasions less incidence of complications. Endocrinological follow-up is easier after total thyroidectomy. CONCLUSIONS: According to our results, we deem the indications for lobectomy have to be limited to the patients having solitary nodule, undoubtedly benign, without familiarity or other environmental risk factor of goitre.
AIM OF THE STUDY: Report as contribution to the controversy between supporters of total thyroidectomy versus "less than total" thyroidectomy. MATERIALS AND METHODS: 42 patient operated on over six years; 35 treated with total thyroidectomy, 7 with lobohystmectomy. RESULTS: In the patients who underwent total thyroidectomy we observed recurrent nerve lesions in 5.7%, hypoparathyroidism in 14.3% and 1 lymph nodal relapse (it was a cancer stay III); in patients who underwent lobohystmectomy, we observed 1 temporary recurrent nerve palsy (14.2%) and 1 lymph nodal relapse (14.2%). DISCUSSION: The choice between total thyroidectomy and lobohystermectomy depends upon different goals: reduction in risk of relapse in total thyroidectomy, to minimize complications in lobohystmectomy. In our series the risk of lymph nodal relapse seems to depend more on biological characters of the tumour than surgical tech of lymphadenectomy; however, this occurrence does not change prognosis. CONCLUSIONS: In our experience, potential multifocality of the disease, low risk of hyatrogenic lesions and easy postoperatory management make total thyroidectomy the our preferred technique. Informed consensus is mandatory in order to involve the patients to the best choice.