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Biomedical subjects

L Santambrogio

Publications and source records attributed to L Santambrogio.

At least 19 recordsLinked to original sources
PubMed2006

Change in gene expression profile induced by alpha-melanocyte stimulating hormone in a malignant mesothelioma cell line.

We have previously reported that the peptide a-melanocyte stimulating hormone (alpha-MSH) has antiproliferative effects in human malignant mesothelioma cells. To determine the molecular mechanisms underlying such effects, we investigated the changes in gene expression profile induced by the alpha-MSH analog [Nle4 -DPhe7 ]-alpha-MSH (NDP-alpha-MSH) in a human malignant mesothelioma cell line. The cDNA macroarray technique revealed changes in expression of genes involved in cell growth, adhesion, signal transduction, and transcription. In particular, NDP-alpha-MSH down-regulated expression of B-Myb and Myc, two oncogenes considered of paramount importance for cell proliferation and cancer. Further, NDP-alpha-MSH exerted a favorable transcriptional regulation of certain integrins and their signaling pathways. Finally, peptide treatment was associated with a prominent inhibition of IL-13, a cytokine with tumor-promoting effects. The data indicate that the influences of alpha-MSH extend beyond the established anti-inflammatory effects in normal cells to include cell cycle regulatory properties in malignant cells.

Cell Cycle Proteins↗
PubMed2005

Unusual presentation of a transparietal cavernous hemangioma of the esophagus.

Hemangiomas are tumors of vascular origin and represent less than 3% of benign neoplasm of the esophagus. We herein report a case of a 55-year-old man, who presented transitory dysphagia and weight loss. A malignancy could not be excluded by a complete work-up, including esophagogram, endoscopic biopsies, CT scan, esophageal endoscopic ultrasonography, PET and thoracoscopic biopsies. Only after partial esophagectomy with laparoscopic gastric mobilization was histological diagnosis obtained. In fact, on microscopic observation of the specimen, the neoplasm appeared to be a cavernous hemangioma of the esophageal submucosa with transparietal extension.

Deglutition Disorders↗
PubMed2004

Positive end-expiratory pressure applied to the dependent lung during one-lung ventilation improves oxygenation and respiratory mechanics in patients with high FEV1.

BACKGROUND AND OBJECTIVE: The aim of this study was to test the efficacy of positive end-expiratory pressure (PEEP) to the dependent lung during one-lung ventilation, taking into consideration underlying lung function in order to select responders to PEEP. METHODS: Forty-six patients undergoing open-chest thoracic surgical procedures were studied in an operating room of a university hospital. Patients were randomized to receive zero end-expiratory pressure (ZEEP) or 10 cmH2O of PEEP to the dependent lung during one-lung ventilation in lateral decubitus. The patients were stratified according to preoperative forced expiratory volume in 1 s (FEV1) as an indicator of lung function (below or above 72%). Oxygenation was measured in the supine position, in the lateral decubitus with an open chest, and after 20 min of ZEEP or PEEP. The respiratory system pressure-volume curve of the dependent hemithorax was measured in supine and open-chest lateral decubitus positions with a super-syringe. RESULTS: Application of 10 cmH2O of PEEP resulted in a significant increase in PaO2 (P < 0.05). This did not occur in ZEEP group, considered as a time matched control. PEEP improved oxygenation only in patients with high FEV1 (from 11.6+/-4.8 to 15.3+/-7.1 kPa, P < 0.05). There was no significant change in the low FEV1 group. Dependent hemithorax compliance decreased in lateral decubitus, more in patients with high FEV1 (P < 0.05). PEEP improved compliance to a greater extent in patients with high FEV1 (from 33.6+/-3.6 to 48.4+/-3.9 mLcmH2O(-1), P < 0.05). CONCLUSIONS: During one-lung ventilation in lateral decubitus, PEEP applied to the dependent lung significantly improves oxygenation and respiratory mechanics in patients with rather normal lungs as assessed by high FEV1.

Analysis of Variance↗
PubMed2004

[Various genetic cardiac diseases predispose to arrhythmias and the risk of sudden death].

Identification of underlying genetic factors has added to understanding of arrhythmogenic triggers and determinants of sudden death. Many factors (medications, bradycardia, temperature changes) during general anesthesia could precipitate malignant dysrhythmia in these patients. Criteria for risk stratification for surgical patients are not available: we can only extrapolate information collected from medical patients. We describe 4 patients with suspected Brugada syndrome (only one was confirmed) during genera anesthesia and propose an anesthesiologic management during operation and for the postoperative period (36 hours).

Anesthesia↗
PubMed2003

Diagnosis of complete mainstem bronchus avulsion by 3-dimensional spiral CT scan of the chest.

Tracheobronchial injury (TBI) after blunt trauma of the chest is a rare life-threatening entity that can be successfully managed by surgery if there is an early diagnosis. A 18-year-old man was injured in a motocycle accident. Three consecutive flexible bronchoscopies risulted negative for tracheo-bronchial lesions. Then, the patient was submitted to a spiral CT-scan of the chest with 3-dimensional reconstruction of the tracheobronchial tree that showed a rupture of the right main bronchus from the trachea. The lesion was successfully treated by surgery. Bronchoscopic findings in TBI may be unclear also for an experienced thoracic surgeon.

Accidents, Traffic↗
PubMed2001

RANTES-induced chemokine cascade in dendritic cells.

Dendritic cells (DC) are the most potent APCs and the principal activators of naive T cells. We now report that chemokines can serve as activating agents for immature DC. Murine bone marrow-derived DC respond to the CC chemokine RANTES (10-100 ng/ml) by production of proinflammatory mediators. RANTES induces rapid expression of transcripts for the CXC chemokines KC and macrophage inflammatory protein (MIP)-2, the CC chemokines MIP-1beta and MIP-1alpha, and the cytokines TNF-alpha and IL-6. Synthesis of KC, IL-6, and TNF-alpha proteins were also demonstrated. After 4 h, autoinduction of RANTES transcripts was observed. These responses are chemokine specific. Although DC demonstrated weak responses to eotaxin, DC failed to respond to other chemokines including KC, MIP-2, stromal-derived factor-1alpha, MIP-1beta, MIP-1alpha, monocyte chemoattractant protein-1, T cell activation gene 3, or thymus-derived chemotactic agent 4. In addition, RANTES treatment up-regulated expression of an orphan chemokine receptor termed Eo1. Chemokine induction was also observed after treatment of splenic DC and neonatal microglia with RANTES, but not after treatment of thymocytes or splenocytes depleted of adherent cells. TNF-alpha-treated DC lose responsiveness to RANTES. DC from mice deficient for CCR1, CCR3, and CCR5 respond to RANTES, indicating that none of these receptors are exclusively used to initiate the chemokine cascade. RANTES-mediated chemokine amplification in DC may prolong inflammatory responses and shape the microenvironment, potentially enhancing acquired and innate immune responses.

Animals↗
PubMed2001

Developmental plasticity of CNS microglia.

Microglia arise from CD45(+) bone marrow precursors that colonize the fetal brain and play a key role in central nervous system inflammatory conditions. We report that parenchymal microglia are uncommitted myeloid progenitors of immature dendritic cells and macrophages by several criteria, including surface expression of "empty" class II MHC protein and their cysteine protease (cathepsin) profile. Microglia express receptors for stem cell factor and can be skewed toward more dendritic cell or macrophage-like profiles in response to the lineage growth factors granulocyte/macrophage colony-stimulating factor or macrophage colony-stimulating factor. Thus, in contrast to other organs, where terminally differentiated populations of resident dendritic cells and/or macrophages outnumber colonizing precursors, the majority of microglia within the brain remain in an undifferentiated state.

Animals↗
PubMed2001

Pulmonary lobectomy for lung cancer: a prospective study to compare patients with forced expiratory volume in 1 s more or less than 80% of predicted.

OBJECTIVE: To compare post-operative course, lung function and survival of lung cancer patients with a forced expiratory volume in 1 s (FEV1) more or less than 80% of predicted submitted to lobectomy. METHODS: The data of patients undergoing lobectomy for non small cell carcinoma at the Thoracic Surgery Unit of the Ospedale Maggiore Policlinico of Milan, Italy, were prospectively collected. Inclusion criteria were a radical resectable tumor with size less than 2.5 cm, negative mediastinal nodes, capability to complete pulmonary function tests, Exclusion criteria were FEV1 <40% of predicted, pre- or post-operative chemo or radiotherapy, lobe to be resected receiving more than 30% of the perfusion, incapacity to quit smoking. RESULTS: Eighty-eight patients entered the study and were divided into two groups according to their FEV1%: 45 patients were included in control group (mean FEV1: 92.2%) and 42 in chronic obstructive pulmonary disease group (mean FEV1: 64.2%). Post-operative complications, operative mortality and actuarial survival were the same in the 2 groups. Six months after lobectomy, the mean changes in FEV1 were -14.9% for first group and -3.2% for second group (P<0.001). CONCLUSION: Lobectomy for cancer can be performed successfully also in selected patients with chronic obstructive pulmonary disease. Post-operative course and survival of these patients is not different from that of patients with normal FEV1, on the contrary, patients with low FEV1 may lose less pulmonary function or even mend it.

Aged↗
PubMed2000

Modulation of experimental autoimmune encephalomyelitis: effect of altered peptide ligand on chemokine and chemokine receptor expression.

Experimental autoimmune encephalomyelitis (EAE) is a T helper 1 (Th1) cell mediated demyelinating disease and the principal animal model for multiple sclerosis. Spinal cords from SJL mice primed with proteolipid protein peptide 139-151 (pPLP) expressed the chemokines RANTES, MCP-1, MIP-2, KC, MIP-1alpha, MIP-1beta, Mig, and fractalkine. We also identified IP-10 in these samples and described a sequence polymorphism in this transcript. Chemokine expression was specific for tissues of the central nervous system. MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical score. Chemokine receptor expression generally correlated with ligand expression. pPLP-primed mice expressed the Th1-associated markers CCR5 and CXCR3 on mononuclear cells. In addition, cells expressing CCR1, CCR2, CCR3, CCR4, CCR8, and CXCR2 were detected. Here we demonstrate that altered peptide ligand (APL)-induced protection from EAE was accompanied by modulation of chemokine and chemokine receptor expression. Spinal cord tissue sections from APL-protected mice showed greatly reduced levels of all chemokines and of CCR1, CCR5, CCR8, CXCR2 and CXCR3. The Th2-associated chemokine receptors CCR3 and CCR4 were found in protected mice, supporting the hypothesis that Th1 but not Th2 cells are down-regulated by APL treatment. This report concludes that chemokines and chemokine receptors can be useful tools to follow modulation of autoimmune disease.

Animals↗
PubMed2000

Induction and suppression of an autoimmune disease by oligomerized T cell epitopes: enhanced in vivo potency of encephalitogenic peptides.

T cell epitope peptides derived from proteolipid protein (PLP139-151) or myelin basic protein (MBP86-100) induce experimental autoimmune encephalomyelitis (EAE) in "susceptible" strains of mice (e.g., SJL/J). In this study, we show that the encephalitogenic effect of these epitopes when injected subcutaneously in complete Freund's adjuvant was significantly enhanced if administered to the animal in a multimerized form as a T cell epitope oligomer (i.e., as multiple repeats of the peptide epitope, such as 16-mers). Oligomer-treated SJL/J mice developed EAE faster and showed a more severe progression of the disease than animals treated with peptide alone. In addition, haplotype-matched B10.S mice, "resistant" to EAE induction by peptide, on injection of 16-mers developed a severe form of EAE. Even more striking, however, was the dramatic suppression of incidence and severity of the disease, seen after single intravenous injections of only 50 microg of the PLP139-151 16-mer, administered to SJL/J mice 7 d after the induction of the disease. Although relapse occurred at about day 45, an additional injection several days before that maintained the suppression. Importantly, the specific suppressive effect of oligomer treatment was also evident if EAE was induced with spinal cord homogenate instead of the single peptide antigen. By contrast, the PLP139-151 peptide accelerated rather than retarded the progression of disease.

Animals↗
PubMed2000

Chronic systemic capillary leak syndrome. Report of a case and review of the literature.

Systemic capillary leak syndrome (SCLS) is a rare condition characterized by recurrent episodes of generalized oedema and severe hypotension, associated with paraproteinaemia. In addition to the acute form, a few cases of chronic SCLS have been reported. We describe a 64-year-old woman who was hospitalized because of a 6-month history of progressive generalized oedema with pericardial and pleural effusions, associated with a serum paraprotein. Clinical and laboratory findings were consistent with a chronic form of SCLS. Treatment with prednisone, furosemide and theophylline was started, which led to a gradual improvement in 2 weeks and a persistent remission after 9 months. This report indicates that SCLS may occur in a chronic form, which seems to be responsive to a therapeutic regimen with prednisone, furosemide, and theophylline.

Capillary Leak Syndrome↗
PubMed1999

Abundant empty class II MHC molecules on the surface of immature dendritic cells.

A monoclonal antibody specific for the empty conformation of class II MHC molecules revealed the presence of abundant empty molecules on the surface of spleen- and bone marrow-derived dendritic cells (DC) among various types of antigen-presenting cells. The empty class II MHC molecules are developmentally regulated and expressed predominantly on immature DC. They can capture peptide antigens directly from the extracellular medium and present bound peptides to antigen-specific T lymphocytes. The ability of the empty cell-surface class II MHC proteins to bind peptides and present them to T cells without intracellular processing can serve to extend the spectrum of antigens able to be presented by DC, consistent with their role as sentinels in the immune system.

Animals↗
PubMed1999

Extracellular antigen processing and presentation by immature dendritic cells.

In antigen presentation to CD4(+) T cells, proteins are degraded to peptide fragments and loaded onto class II MHC molecules in a process involving the peptide exchange factors H-2M (murine) or HLA-DM (human). In many antigen-presenting cells these processes occur in intracellular endosomal compartments, where peptides are generated and loaded onto class II MHC proteins for subsequent transport to the surface and presentation to T cells. Here, we provide evidence for an additional antigen-processing pathway in immature dendritic cells (DC). Immature DC express at the cell surface empty or peptide-receptive class II MHC molecules, as well as H-2M or HLA-DM. Secreted DC proteases act extracellularly to process intact proteins into antigenic peptides. Peptides produced by such activity are efficiently loaded onto cell surface class II MHC molecules. Together these elements comprise an unusual extracellular presentation pathway in which antigen processing and peptide loading can occur entirely outside of the cell.

Animals↗
PubMed1999

Antigen presenting capacity of brain microvasculature in altered peptide ligand modulation of experimental allergic encephalomyelitis.

Co-immunization with an altered peptide ligand (LR) partially protects SJL mice from proteolipid protein peptide 139-151-induced experimental allergic encephalomyelitis [Kuchroo, V.K., Greer, J.M., Kaul, D., Ishioka, G.Y., Franco, A., Sette, A., Sobel, R.A., Lees, M.B., 1994. A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a diverse T cell repertoire. J. Immunol. 153, 3326-3336; Santambrogio, L., Lees, M.B., Sobel, R.A., 1998. Altered peptide ligand modulation of experimental allergic encephalomyelitis: immune responses within the CNS. J. Neuroimmunol. 81, 1-13]. Clinical protection was noted despite extensive central nervous system inflammation observed after co-immunization with native and altered peptides. To extend our previous reports on this model, we now compare MHC class II expression and antigen presenting cell activity of cells associated with the blood-brain barrier in diseased and protected mice. Immunohistochemical studies identified MHC class II products on both the endothelial and microglial/macrophage populations. Ex vivo experiments suggested a correlation between the reduced clinical disease observed in the co-immunized mice and the antigen presenting activity of cells at the blood-brain barrier. The results suggest that antigen presenting activity is primarily mediated by macrophage-lineage cells of the central nervous system.

Animals↗
PubMed1998

Altered peptide ligand modulation of experimental allergic encephalomyelitis: immune responses within the CNS.

An altered peptide ligand (analog) of the encephalitogenic epitope of proteolipid protein residues 139-151 (p139-151) in which residues 144 and 147 are substituted with leucine and arginine, respectively (LR), protects from clinical but not histological experimental allergic encephalomyelitis (EAE). To understand in situ events associated with this protection, T cells from brains of mice immunized with either native p139-151, the analog LR or a combination of the two were isolated and characterized. High proportions of cells from co-immunized mice (38%) and LR-immunized mice (58%) reacted to both p139-151 and LR, whereas fewer cells from p139-151 immunized mice (7%) were cross-reactive. T cell clones derived from brains of LR- and co-immunized mice were also cross-reactive in vitro. By reverse transcriptase-based polymerase chain reaction, higher levels of TGF-beta mRNA, and lower levels of TNF-alpha and IFN-gamma mRNA were found in the central nervous system (CNS) tissue of LR and co-immunized mice. Immunohistochemistry demonstrated greater TGF-beta immunoreactivity in CNS inflammatory foci in co-immunized and LR-immunized mice. There were no significant differences in CD4+ or CD8+ cell infiltrates among the groups and differences in other cytokines were not identified by immunocytochemistry. Protection from clinical EAE in LR and co-immunized mice was partially abolished by anti-TGF-beta antibody treatment. Thus, protection from clinical disease following immunization with the analog LR is associated with infiltration into the CNS of a T cell population that could potentially recognize the native PLP peptide and with enhanced TGF-beta production by cells within CNS inflammatory foci.

Animals↗
PubMed1998

Buttressing staple lines with bovine pericardium in lung resection for bullous emphysema.

The utility of buttressing an endoscopic mechanical stapler with strips of bovine pericardium in resection of pulmonary bullous areas was evaluated by comparing the duration of air leakage in two randomized patient groups, one with and one without buttressing. The duration of air leakage was not related to bulla size in either group but showed a linear relation with the radiologic emphysema score in both groups (p < 0.001) and was shorter when the stapler had been fitted with bovine pericardium, but significantly reduced (p = 0.019) only in patients with a high emphysema score. The duration of air leakage was thus related to emphysema score, and in patients with high scores was shortened by application of bovine pericardium to the stapler.

Adult↗