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S Salvi

Publications and source records attributed to S Salvi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Efficient simultaneous presentation of NY-ESO-1/LAGE-1 primary and nonprimary open reading frame-derived CTL epitopes in melanoma.

Recent studies have shown that CTL epitopes derived from tumor-associated Ags can be encoded by both primary and nonprimary open reading frames (ORF). In this study we have analyzed the HLA-A2-restricted CD8(+) T cell response to a recently identified CTL epitope derived from an alternative ORF product of gene LAGE-1 (named CAMEL), and the highly homologous gene NY-ESO-1 in melanoma patients. Using MHC/peptide tetramers we detected CAMEL(1-11)-specific CD8(+) T cells in peptide-stimulated PBMC as well as among tumor-infiltrated lymph node cells from several patients. Sorting and expansion of tetramer(+) CD8(+) T cells allowed the isolation of tetramer(bright) and tetramer(dull) populations that specifically recognized the peptide Ag with high and low avidity, respectively. Remarkably, only high avidity CAMEL-specific CTL were able to recognize Ag-expressing tumor cells. A large series of HLA-A2-positive melanoma cell lines was characterized for the expression of LAGE-1 and NY-ESO-1 mRNA and protein and tested for recognition by CAMEL-specific CTL as well as CTL that recognize a peptide (NY-ESO-1(157-165)) encoded by the primary ORF products of the LAGE-1 and NY-ESO-1 genes. This analysis revealed that tumor-associated CD8(+) T cell epitopes are simultaneously and efficiently generated from both primary and nonprimary ORF products of LAGE-1 and NY-ESO-1 genes and, importantly, that this occurs in the majority of melanoma tumors. These findings underscore the in vivo immunological relevance of CTL epitopes derived from nonprimary ORF products and support their use as candidate vaccines for inducing tumor specific cell-mediated immunity against cancer.

Animals↗
PubMed2000

Biochemical analysis of HLA class I subunits expression in breast cancer tissues.

The expression of HLA class I alpha-chain and beta(2)-m subunits was studied at the protein level by a semiquantitative Western blot (WB) approach, in 25 primary breast tumors. The results indicated three pathways of alterations defined comparing the tumor WB gel band with the corresponding PBL gel band: (i) high downregulation pattern (the tumor WB gel band was < or =50% relative to the PBL band), which was found in 44% and 36% of tumors for alpha-chain and beta(2)-m, respectively; (ii) low downregulation pattern (the tumor gel band was between 51% and 75%), which was found in 24% and 20% of tumors for alpha-chain and beta(2)75%), which was found in 32% and 44% of tumors for alpha-chain and beta(2)-m, respectively. The concordance rate with immunohistochemistry (IHC) performed on the same tissue samples was 72% for alpha-chain and 64% for beta(2)-m. This study shows that the use of a semiquantitative WB technique can well define the levels of HLA class I antigens in an autologous setting allowing the biochemical analysis of HLA class I downregulation directly in solid tumor tissues. In addition, the WB technique can be a valuable tool to objectively support the IHC method.

Blotting, Western↗
PubMed2000

Bilateral open treatment of spontaneous pneumothorax: a new access.

A new technique for bilateral apical bullectomy and pleurectomy via axillary minithoracotomy and transmediastinal access to the contralateral side, was used in 13 patients with bilateral apical blebs and/or pneumothorax. The contralateral space is reached at the posterior superior mediastinum, passing between the first thoracic vertebral bodies (T1-T4) and the oesophagus. The contralateral lung apex is then pulled into the thoracotomy side and apical bullectomy carried out by linear stapler. The obvious advantages of avoiding a second thoracotomy while providing complete solution to the clinical problem are particularly important in young patients with spontaneous pneumothorax caused by bilateral apical blebs.

Chest Tubes↗
PubMed2000

Patterns of systolic stress distribution on mitral valve anterior leaflet chordal apparatus. A structural mechanical theoretical analysis.

Increasing diffusion and complexity of mitral valve repair procedures may prompt an interest in the evaluation of the patterns of stress distribution on the chords, which are, from the structural mechanical point of view, the weakest element of valve apparatus. This theoretical analysis concentrates in particular on the mitral valve anterior leaflet. As is known, the vast majority of the chordae are attached to the anterior leaflet within the coaptation area; during systole they are then necessarily parallel, aligned along the same plane as that of the leaflets' coaptation surface, to which they are attached; moreover the thickness of the chordae increases significantly from the marginal chordae to the more central ones. In normal conditions during systole the progressively wider coaptation surface causes the increasing stress to be supported by an increasing number of progressively thicker chords, which are substantially parallel and aligned on the coaptation surface plane in such a way that they can share the stress between them, according to their thickness; in other words chords form a multifilament functional unit which enrolls elements of increasing thickness in response to the mounting stress. The geometrical modifications of the valve apparatus architecture (annulus dilatation, leaflet retraction, chordal elongation or retraction) often associated with valve insufficiency due to chordal rupture, have the common result of causing, during systole, a radial disarrangement of the direction of most of the secondary chordae which are no longer parallel, aligned on the coaptation surface plane. Due to the negligible elastic module of the valve leaflet, in this new arrangement the various chordae cannot share the stress between themselves as they do in a normal physiological situation; on the contrary the thinner chordae nearer to the free margin are also loaded with the peak systolic stress, thus generating conditions favoring their rupture. It can, therefore, be hypothesized that the anatomopathological picture of valve insufficiency due to chordal rupture may be the final event of a series of geometrical modifications of valve apparatus architecture, the common consequence of which is to load thinner marginal chords with peak systolic stress from which they are normally spared, thus favoring their rupture.

Animals↗
PubMed1999

cDNA and protein characterization of human MAGE-10.

MAGE genes are frequently expressed in several types of human malignancy and code for antigens recognized by cytotoxic T lymphocytes. We have previously described a monoclonal antibody (MAb), named 6C1, that recognizes the MAGE-1 protein and cross-reacts with a 72-kDa protein present in lysates of melanoma cells such as MZ2-MEL. To identify this protein, we have screened an expression library prepared from MZ2-MEL cells. Several clones that encoded a protein recognized by antibody 6C1 contained a sequence identical to that of MAGE-10, another member of the MAGE-A gene family. Full-length MAGE-10 cDNA clones, obtained after screening additional cDNA melanoma libraries, were found to be approximately 2.5 kb in length. In vitro translation and transient transfection experiments indicated that MAGE-10 codes for a protein of approximately 72 kDa. This product was recognized by MAb 6C1 as well as by a polyclonal serum raised against a MAGE-10 peptide, thus demonstrating its identity with MAGE-10. Analysis of MAGE-10 mRNA by RT-PCR confirmed its presence in testis and placenta but not in other normal tissues. Expression of MAGE-10 in melanoma tumors was found to parallel that of MAGE-1. Western blot analysis with the polyclonal anti-MAGE-10 antibody showed the presence of MAGE-10 in lysates of purified trophoblast cells. Immuno-cytochemistry of cultured melanoma cells indicated that MAGE-10 is a nuclear protein.

Antibodies, Monoclonal↗
PubMed1999

The clinical impact of dynamic intraventricular obstruction during dobutamine stress echocardiography.

We selected 73 consecutive patients without myocardial-infarction, hypertrophic cardiomyopathy or hypertension complaining of effort chest discomfort/dyspnoea, and/or reporting exercise ischaemic ECG changes, and submitted them to simultaneous dobutamine stress echocardiography (DSE) and 99mTc tetrofosmin SPECT (T SPECT) and to coronary angiography to evaluate the clinical impact of intraventricular obstruction (IVO) during dobutamine infusion. Sixteen patients (22%, 7 males, mean age+/-SD 63+/-8 years, group 1) developed IVO (mean CW Doppler velocity+/-SD: 3.8+/-1.0 m/s) and 57 (41 males, mean age+/-SD 63+/-10 years, group 2) did not. The two groups had similar incidence of angina and ischaemic ECG changes at exercise tolerance test. DSE did not demonstrate wall motion abnormalities in any group 1 patient while T SPECT showed a perfusion defect in the only one with coronary artery disease (CAD). DSE reproduced symptoms in a higher percentage of patients with than without IVO, while there was no statistical difference in the reproduction of ischaemic ECG changes, despite CAD prevalence was much lower in group 1. Group 1 patients remained asymptomatic on beta-blockers at 12-month follow-up. Dobutamine-induced IVO, by reproducing symptoms, suggests that IVO plays a role in the clinical setting in patients without CAD complaining of unexplained reduced effort tolerance who should undergo DSE.

Adult↗
PubMed1999

High frequency of T cell clonal expansions in primary human melanoma. Involvement of a dominant clonotype in autologous tumor recognition.

It was previously found that primary melenomas from HLA-A2-matched patients display an increased expression of a few T cell receptor (TCR) variable-region beta-chain transcripts (BV) compared with autologous peripheral blood lymphocytes (PBL) and uninvolved skin. In order to see whether expansions of clonal/oligoclonal subsets of T cells occurred, complementarity-determining region 3 (CDR3) of BV transcripts overexpressed in the neoplastic infiltrate were cloned and sequenced. Dominant rearrangements were found for BV14, which were commonly increased in the neoplastic lesions of all analysed HLA-A2 melanoma patients, as well as for other overexpressed BV gene families, but none of them could be identified among autologous PBL. No identical CDR3 sequences could be detected in the dominant BV14 rearrangements obtained from the different patients. In one patient a single clonally expanded SLSGTGVNEQF CDR3 clonotype accounted for the entire BV14 relative frequency of expression (24%) in tumor-infiltrating lymphocytes (TIL). Two independent mixed lymphocyte/tumor cultures (MLTC) could be successfully established from TIL of the patient and were found to exert HLA-class-I-restricted cytotoxicity for the autologous melanoma line. BV14 T cells that constituted from 22% to 32% of all T cells present in both MLTC lines, as assessed by flow cytometry, all displayed the same CDR3 clonotype found in vivo and could be shown, by TCR down-modulation experiments, to be involved in autologous tumor recognition. These results support the hypothesis of a tumor-antigen-driven origin of clonally amplified T cells present at high frequency in the in situ neoplastic infiltrate.

Clone Cells↗
PubMed1999

Could the airway epithelium play an important role in mucosal immunoglobulin A production?

Immunoglobulin (Ig) A is the major immunoglobulin of the healthy respiratory tract and is thought to be the most important immunoglobulin for lung defence. The basis for the preferential generation of IgA-secreting cells in the airway mucosa remains unclear. Given the half-life of 5 days for the majority of IgA plasma cells, many IgA plasma cells must develop daily from B cells to guarantee a continuous supply of IgA antibodies in the airway mucosa. For this, the surrounding cells must provide a constant supply of cytokines necessary for B-cell isotype switch, growth and differentiation into IgA-secreting plasma cells. Studies with CD4+ T-cell knockout mice, T-cell receptor knockout mice and mice made transgenic for CTLA4-Ig demonstrate normal mucosal IgA isotype switch, differentiation and IgA production, thereby suggesting that T cells are not critical for mucosal IgA production, and that other cell sources may be more important. Also, the bronchus-associated lymphoid tissue (BALT), which is believed to be the major site where IgA isotype switch and differentiation of B cells into plasma cells occur with the help of cytokines released by T cells, is not a constitutive feature of the normal human lung. This indicates that other parts of the respiratory tract must carry out the BALT function. We have recently demonstrated that healthy human airway epithelial cells constitutively produce IL-5, a major cytokine implicated in the growth and differentiation of post-switch mIgA+ B cells to IgA-producing plasma cells. Several studies have recently reported that the human airway epithelium also constitutively produces IL-2, TGFbeta, IL-6 and IL-10, factors which are essential for B-cell clonal proliferation, IgA isotype switch and differentiation into IgA-producing plasma cells. The close proximity of B cells to the airway epithelium probably ensures a constant supply of growth and differentiation factors necessary for mucosal IgA production. In addition, the epithelial cells produce a glycoprotein, called the secretory component, which not only confers increased stability to S-IgA, but is also quantitatively the most important receptor of the mucosal immune system, since it is responsible for the external transport of locally produced polymeric IgA and IgM. Recent studies also suggest a possible role for epithelial cells in antigen presentation. Dendritic cells situated within the airway epithelium could directly present antigens to B cells and direct their isotype switch towards IgA1 and IgA2 with the help of cytokines produced by epithelial cells. Airway epithelial cells could therefore play a major role in the production of mucosal IgA antibodies which are essential for airway mucosal defence.

Animals↗
PubMed1999

Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers.

Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the impact of DE on human airways, we exposed 15 healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue. Significant increases in neutrophils and platelets were observed in peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response in healthy human volunteers, which is underestimated by standard lung function measurements.

Adult↗
PubMed1999

Interleukin-5 production by human airway epithelial cells.

Interleukin (IL)-5 is a pleiotropic cytokine that exhibits biologic activity on cells of diverse hemopoieitic lineages. IL-5 enhances mediator release from human basophils and plays a pivotal role in the chemoattraction, proliferation, differentiation, survival, and activation of eosinophils. Th2- and Tc2-like T cells, mast cells, basophils, and eosinophils are the known cellular sources of this cytokine. Using a sensitive and novel reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay system, we found that IL-5 messenger RNA (mRNA) was constitutively expressed in bronchial biopsies obtained from healthy individuals, and that the levels of IL-5 mRNA expression decreased 1. 5 h after exposure to 0.12 ppm ozone for 2 h. Because the oxidative effects of ozone are confined to the epithelial cell surface and it is known that ozone induces epithelial damage and shedding, we hypothesized that epithelial cells might be a source of IL-5 mRNA. We demonstrate here that both transformed human bronchial epithelial cell lines (A549 and 16HBE14o-) and primary human bronchial and nasal epithelial cells grown in culture constitutively express IL-5 mRNA, which is upregulated on stimulation with tumor necrosis factor (TNF)-alpha. Culture supernatants derived from A549 cells exposed to TNF-alpha and interferon-gamma demonstrated detectable levels of IL-5 protein, and immunostaining of bronchial biopsies obtained from healthy human airways revealed the presence of IL-5 protein localized to the bronchial epithelium. To our knowledge, this is the first report demonstrating IL-5 production by human airway epithelial cells. This observation provides further evidence for the role of airway epithelium in regulating airway immune responses, in particular enhancing chemotaxis, activation, and survival of eosinophils, which could play an important role in the pathogenesis of bronchial asthma.

Adult↗
PubMed1999

Descending aorta substitution with expandable ends prosthesis. Case report.

A case of esophageal cancer infiltrating the left bronchus pars membranacea and the aneurysmal aortic wall was resected en bloc with the bronchial and aortic wall. Descending aorta was substituted by means of a Dacron prosthesis fitted with expandable devices at both ends, allowing a very significant reduction of the clamping time and simplification of this part of the procedure.

Aortic Aneurysm, Abdominal↗
PubMed1999

[Longitudinal bronchotomy on the pars membranacea for endoscopic foreign body extraction].

Purpose of this paper is to report a case of foreign body obstructing the middle lobe bronchial origin, surgically removed through a longitudinal bronchotomy on the pars membranacea, reached by passing posteriorly to the lung. Anatomical considerations suggest that longitudinal bronchotomy on the pars membranacea of the main bronchial axis (stem bronchi, intermedius br (right), and lower lobar bronchus) gives direct visualization from inside also of foreign bodies sited into the lobar bronchi (sup, middle and lingula), allowing an easy bronchotomy repair, without lumen distortion or stenosis. Since the pulmonary artery is not in contact with this pars membranacea, broncho-arterial fistula in case of suture line dehiscence is quite improbable.

Bone and Bones↗
PubMed1997

Prosthesis for aortic arch substitution.

BACKGROUND: The risk of neurologic complications in aortic arch prosthetic substitution is directly related to the duration of the circulatory arrest. The purpose of this article is to report the experiments on animals of a device for simplifying and quickening the vascular anastomosis in aortic arch substitution. METHODS: The device consists of expandable loops of stainless steel wire, sewn to the proximal end of a Dacron prosthesis. An actuating removable guide allows the stainless steel wire loops to be expanded and tightened, in such a way that the prosthesis diameter is varied, while maintaining a regular cylindric shape. The prosthesis end is then transformed into a rigid cylindrical ring, approximately half the maximal diameter in length, with a variable and controllable diameter. A composite graft was prepared, fitted with the expandable device at the distal end of the main prosthesis as well as at each end of the branches for the supraaortic trunks. Cardiopulmonary bypass was established by cannulation of the right atrium and left iliac artery. The prosthesis was positioned very easily and quickly during a brief hypothermic circulatory arrest; ascending aorta anastomosis was carried out by the standard technique after central nervous system reperfusion was resumed. Acute experiments were carried out in 5 swine. RESULTS: Four of 5 animals survived the procedure without detectable neurologic sequelae. At sacrifice the prosthesis was found to be properly sited without lumen distortion or thrombosis. CONCLUSIONS: The main advantages of this device and modality of arch substitution in a clinical setting would include drastic reduction of the circulatory arrest time, easy and reliable hemostasis of the anastomosis line, and accurate and firm approximation of the dissection layers in case of dissecting aneurysms.

Animals↗
PubMed1996

Aortic wall structural strengthening by intraluminal net prosthesis to arrest aneurysm progression and to prevent dissection and rupture.

The major limitation implicit in the endovascular procedures for aortic prosthetic substitution is that they cannot be used in those tracts of the aorta where important collateral branches originate (aortic arch, thoraco-abdominal tract, upper abdominal), that would be occluded by the prosthesis. In order to overcome this limitation we hypothesized the endovascular positioning of a prosthesis in the form of a wide mesh network that would be gradually and spontaneously covered by new intima and included in the aortic wall. The fabric framework linked to the aortic wall would then condition its significant, regular and uniform mechanical strengthening that fractionates and partially absorbs the centrifuge pulsatile stress of the bloodstream. The purpose of this paper is to report the results of the insertion of a braided Prolene net prosthesis in the first 7 cm of the descending aorta of ten swine. The animals were killed after 6 weeks, the substituted segment removed and aortic wall compliance measured under standardized conditions. The prosthesis was found entirely covered by new intima, well embodied in the aortic wall. The intercostal collateral included in the substituted segment was patent, as proved by bubble formation during underwater insufflation. Compliance of the prosthesis segment was significantly lower than that of the adjacent descending aorta. Histology showed a regular net prosthesis inclusion deep in the neo-intima layer. Present results indicate the technical feasibility of the procedure, achieving significant aortic wall strengthening without affecting the collateral (intercostal) circulation.

Aortic Dissection↗