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L Beretta

Publications and source records attributed to L Beretta.

At least 19 recordsLinked to original sources
PubMed2006

Validity of the Saint George's Respiratory Questionnaire in the evaluation of the health-related quality of life in patients with interstitial lung disease secondary to systemic sclerosis.

OBJECTIVES: Interstitial lung disease (ILD) profoundly affects the health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc). We tested the validity of the Saint George's Respiratory Questionnaire (SGRQ), a lung-specific HRQoL-evaluation tool, in a population of SSc patients with ILD. METHODS: Twenty-eight consecutive SSc patients with a restrictive pulmonary involvement, defined as a forced vital capacity <80% of the predicted, with no pulmonary hypertension were considered. All the patients filled in the Medical Research Council (MRC) scale for perceived breathlessness, the SGRQ and the Disability Index of the Health Assessment Questionnaire (HAQ DI), and underwent evaluation with complete pulmonary function testing (PFT), 6-minute walk distance (6MWD) and high-resolution computed tomography (HRCT). RESULTS: The SGRQ 'activity' scores inversely correlated with the 6MWD (r = -0.86, P < 0.001) and forced vital capacity percentage of predicted values (r = -0.47) and directly correlated with HRCT (r = 0.41, P < 0.05), MRC (rho = 0.64, P < 0.001) or HAQ DI scores (r = 0.62, P < 0.001), independently of disease duration or subset. On the contrary, HAQ DI scores were influenced by those variables and corrected correlations with 6MWD (r = 0.56, P < 0.001) or HRCT scores (r = 0.36, P = NS) were less strong than those observed with the SGRQ. CONCLUSIONS: The SGRQ, although not specifically designed for scleroderma, is a valid respiratory-specific questionnaire for the evaluation of HRQoL in patients with SSc-related ILD. The SGRQ performs better in relation to exercise capacity and lung imaging than other non-respiratory-specific questionnaires widely used in scleroderma studies. Further studies are needed to address its ability to assess changes over time or in response to therapy.

Adult↗
PubMed2006

Proteomics for the early detection and treatment of hepatocellular carcinoma.

The prognosis for hepatocellular carcinoma (HCC) is poor and has not improved in recent years, largely owing to lack of early diagnosis, frequent recurrence after surgery and resistance to chemotherapy. Proteomics holds the promise of improving our understanding of HCC carcinogenesis and progression as well as of discovering novel diagnostics and therapeutics. Proteomic analyses of HCC cell lines, animal models and serum and tumor tissue from patients with HCC have been performed to date. Proteomic technologies have greatly improved in the past few years as reviewed here. It is anticipated that with the recent development of protein tagging, protein separation methods and mass spectrometry sensitivity, proteomic studies of HCC will allow the identification of diagnostic and prognostic biomarkers as well as therapeutic targets, which could greatly improve the clinical management of HCC patients.

Animals↗
PubMed2006

HLA-B35 upregulates the production of endothelin-1 in HLA-transfected cells: a possible pathogenetic role in pulmonary hypertension.

HLA-B35 is associated with an increased risk for developing isolated pulmonary hypertension (iPHT) in systemic sclerosis, but the mechanisms underlying this association have not been fully elucidated yet. Endothelin-1 (ET-1) is the main pathogenetic molecule implied in the development of iPHT; therefore, we sought to determine if ECV304 cells transfected with the HLA-B35 allele produce increased amounts of ET-1 after incubation with physiological concentrations of interleukin-1 beta (IL-1beta). ECV304 cells transfected with HLA-B*3501 and HLA-B*0801 polymorphic alpha chain or with pIRESneo2 were incubated with 100 U/ml of IL-1beta for 6, 12, 24, 36 and 48 h. ET-1 levels were determined using EIA kit (CAYMAN Chemical, Ann Arbor, MI) in supernatants from different cell cultures; the relative expression of the preproendothelin-1 (PPET-1) gene was also determined by reverse transcription-polymerase chain reaction. Cells expressing the HLA-B35 allele showed significantly increased levels of ET-1 at all the selected times compared with controls or HLA-B8-transfected cells. The relative expression of the PPET-1 gene was also increased in a proportionally direct manner. The HLA-B35 allele influences the production of ET-1 in HLA-B35-transfected ECV304 cells by promoting the expression of its precursor, PPET-1. Our results provide an explanation for the epidemiological association existing between iPHT and HLA-B35.

Alleles↗
PubMed2005

An Italian survey of severe head trauma management during extracranial surgery.

BACKGROUND AND OBJECTIVE: Anaesthetic drugs and procedures interfere with secondary brain injury following severe head trauma, yet studies regarding the anaesthetic management of these patients are lacking. We investigated the behaviour of Italian anaesthetists regarding this topic. METHODS: A questionnaire investigating the approach to a patient with severe head trauma requiring an urgent splenectomy for ruptured spleen was sent to 250 Italian anaesthetists. Questions regarded the pre-, intra- and postoperative phases, and concerned the rationale use and availability of specific monitoring systems, and indications for invasive procedures and use of drugs, fluids and blood products. RESULTS: There were 162 (64.8%) responders. Seventy-five percent believed that early tracheal intubation within the emergency room was necessary, while 25% postponed it to the operating room. Basic monitoring was defined as essential by all responders, 147 (90.7%) considered invasive arterial pressure monitoring to be essential. Fifty-seven (84%) anaesthetists working in hospitals without neurosurgical facilities would have transferred the patient after splenectomy. Prophylactic hyperventilation was frequently used (36%). Sixty-eight percent of responders would have preferred in intracranial pressure monitoring inserted before laparotomy, but only 35% actually had this possibility. In case of acute intraoperative arterial hypotension after splenectomy, 54% of the responders advocated the use of blood or blood products to optimize peripheral oxygen transport. CONCLUSIONS: More widespread knowledge of certain areas of severe head trauma management such as early tracheal intubation, avoidance of prophylactic hyperventilation, adequate invasive monitoring, appropriate use of blood products, and timing of transfer to hospitals with neurosurgical facilities is needed.

Anesthesia↗
PubMed2001

Activation of the interferon-inducible protein kinase PKR by hepatocellular carcinoma derived-hepatitis C virus core protein.

Hepatitis C virus (HCV) is a major etiological agent of chronic liver disease and hepatocellular carcinoma (HCC). We demonstrate herewith that HCV core proteins encoded by sequences isolated from HCC tumor tissues, but not those derived from their non-tumor counterparts in the same liver, co-localise in vitro and in vivo and co-immunoprecipitate with PKR in hepatocytic Huh7 cells. We show that this association in fact augments the autophosphorylation of PKR and the phosphorylation of the translation initiation factor eIF2alpha, which are two markers of PKR activity. The present study therefore identifies a novel model of virus-cell interactions whereby a viral protein, the HCV core, activates PKR activity.

Amino Acid Sequence↗
PubMed2001

Profiling changes in gene expression during differentiation and maturation of monocyte-derived dendritic cells using both oligonucleotide microarrays and proteomics.

Dendritic cells (DCs) are antigen-presenting cells that play a major role in initiating primary immune responses. We have utilized two independent approaches, DNA microarrays and proteomics, to analyze the expression profile of human CD14(+) blood monocytes and their derived DCs. Analysis of gene expression changes at the RNA level using oligonucleotide microarrays complementary to 6300 human genes showed that approximately 40% of the genes were expressed in DCs. A total of 255 genes (4%) were found to be regulated during DC differentiation or maturation. Most of these genes were not previously associated with DCs and included genes encoding secreted proteins as well as genes involved in cell adhesion, signaling, and lipid metabolism. Protein analysis of the same cell populations was done using two-dimensional gel electrophoresis. A total of 900 distinct protein spots were included, and 4% of them exhibited quantitative changes during DC differentiation and maturation. Differentially expressed proteins were identified by mass spectrometry and found to represent proteins with Ca(2+) binding, fatty acid binding, or chaperone activities as well as proteins involved in cell motility. In addition, proteomic analysis provided an assessment of post-translational modifications. The chaperone protein, calreticulin, was found to undergo cleavage, yielding a novel form. The combined oligonucleotide microarray and proteomic approaches have uncovered novel genes associated with DC differentiation and maturation and has allowed analysis of post-translational modifications of specific proteins as part of these processes.

Amino Acid Sequence↗
PubMed2001

Translational control of the proteome: relevance to cancer.

Translational control is an important but relatively unappreciated mechanism that regulates levels of protein products. In addition to a global translational control that regulates the cell's response to external stimuli such as growth factors, cytokines, stress and viral infections, selective translational control has recently been demonstrated to affect many genes related to growth and apoptotic processes. Modifications in the 5'untranslated region of these specific mRNAs may lead to an up-regulation of the protein product by as much as 100-fold. Translational infidelity has been reported in some human cancers for oncogenes such as c-myc and mdm2. Furthermore, modulation of selective translational control has also been demonstrated in cells over-expressing the translation initiation factor elF4E. Elevated levels of elF4E were found in a broad spectrum of solid tumors (breast, head and neck, colon and bladder carcinomas as well as in non-Hodgkin's lymphomas). Other translation initiation factors and translation components such as elongation factors and ribosomal proteins have also been reported to be overexpressed in some human tumors. This review discusses the relevance of these observations to a cell's proteome and for tumorigenesis and how the genomics and proteomics can be used to advance our understanding of the role of translational control in cancer.

Eukaryotic Initiation Factor-4E↗
PubMed2001

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study.

BACKGROUND: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. AIM: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. METHODS: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. RESULTS: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. CONCLUSIONS: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.

Administration, Oral↗
PubMed2001

Expression of hepatitis C virus NS5A natural mutants in a hepatocytic cell line inhibits the antiviral effect of interferon in a PKR-independent manner.

The impact of hepatitis C virus NS5A protein mutations on interferon alfa (IFN-alpha) signaling pathway, cell proliferation, and viability is an important issue that is still under debate. We have therefore combined transient and stable expression in a human hepatocytic cell line (Huh7) of 3 full-length NS5A sequences, isolated from patients with or without response to IFN-alpha therapy. Expression of all 3 NS5A-reduced IFN-alpha global antiviral activity on both vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) replication. We did not show, however, an effect of these 3 NS5A proteins on double-stranded RNA-dependent kinase (PKR) expression and activity as well as colocalization and coimmunoprecipitation between NS5A and PKR. We also failed to show an effect of the 3 NS5A mutants tested on cell proliferation and viability. Overall, our results support an important role of NS5A in controlling IFN-alpha antiviral activity; they show, however, that PKR-independent mechanisms are implicated, at least in liver-derived cells.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Proteomic-based approach for the identification of tumor markers associated with hepatocellular carcinoma.

There is increasing evidence for an immune response to cancer in humans, demonstrated in part by the identification of autoantibodies to tumor antigens. The identification of panels of tumor antigens that elicit a humoral response may have utility in cancer screening, diagnosis or in establishing prognosis. Several approaches are currently available for the identification of tumor antigens. We have used a proteomic-based approach for the identification of tumor antigens that induce an antibody response which we have applied to hepatocellular carcinoma, a major type of cancer worldwide. Two-dimensional gel electrophoresis allows simultaneous separation of several thousand individual proteins from tumor tissue or tumor cell lines. Proteins eliciting a humoral response in HCC were identified by 2-D Western blotting using sera from patients with hepatocellular carcinoma, followed by mass spectrometry analysis and database search. The common occurrence of autoantibodies to specific proteins may have utility for HCC screening and diagnosis.

Antigens, Neoplasm↗
PubMed2000

Neuro-Link, a computer-assisted database for head injury in intensive care.

Reliable information is vital for clinical trials, so we developed a database, for head trauma victims admitted to neuro-intensive care units (NICU). This database, first step in a sequential project, comprises 176 selected fields mainly focused on the early post-traumatic phase and has a user-friendly computerized interface. The software was tested for a trimester in 18 Italian neuro-intensive care units. The paper describes the main features of the database, the results of a three months' data collection test, its limitations and its potential improvements. A description of the database fields and a brief summary of the 282 patients included so far are also presented.

Adolescent↗
PubMed2000

Defect in the regulation of 4E-BP1 and 2, two repressors of translation initiation, in the retinoid acid resistant cell lines, NB4-R1 and NB4-R2.

We recently reported evidence for differential regulation of the translation machinery during human myeloid differentiation, specific to the monocytic/macrophage pathway or to the granulocytic pathway. A decrease in translation rates and concomitant regulation of two repressors of translation initiation, 4E-BP1 and 4E-BP2 (eIF4E-binding proteins 1 and 2), occur in cells induced to differentiate along the monocytic/macrophage pathway or along the granulocytic pathway. Induction of HL-60 and U-937 cell differentiation into monocytes/macrophages results in a dephosphorylation and consequent activation of 4E-BP1. In contrast, following treatment of HL-60 cells with retinoic acid (RA) which results in a granulocytic differentiation of these cells, 4E-BP1 protein expression is decreased whereas 4E-BP2 protein expression is strongly increased. In this study, we further investigated the regulation of 4E-BP1 and 4E-BP2 in the RA-induced differentiation process using the NB4 promyelocytic cell line and the RA maturation-resistant NB4 subclones, NB4-R1 and NB4-R2. RA treatment resulted in a decrease in 4E-BP1 protein and mRNA expression and concomitant increase in 4E-BP2 protein expression, in NB4 cells, but not in NB4-R1 and NB4-R2 cells. The increase in 4E-BP2 protein expression was not correlated to an increase in 4E-BP2 mRNA level suggesting a post-transcriptional regulation of 4E-BP2 expression. In RA-primed cells, cAMP induce maturation of NB4-R1, but not NB4-R2 cells. cAMP treatment resulted in a down-regulation of 4E-BP1 protein and mRNA expression in RA-primed NB4-R1, but not NB4-R2 cells. However, 4E-BP2 expression was not modified in both cell types following cAMP treatment. This indicates that 4E-BP1 down-regulation is associated with granulocytic maturation, whereas post-transcriptional regulation of 4E-BP2 expression is associated with the early action of RA.

Adaptor Proteins, Signal Transducing↗
PubMed2000

The natural history of ulcerative proctitis: a multicenter, retrospective study. Gruppo di Studio per le Malattie Infiammatorie Intestinali (GSMII).

OBJECTIVE: The aim of this study was to evaluate the clinical features and the long term evolution of patients with a well defined initial diagnosis of ulcerative proctitis. METHODS: Patients with an original diagnosis of ulcerative proctitis who had been seen at any of 13 institutions from 1989 to 1994 were identified. Data on disease onset and subsequent evolution were recorded. In addition, 575 patients with more extensive disease, treated in the same centers, were used as controls. RESULTS: A total of 341 patients satisfied the inclusion criteria. The percentage of smokers in these patients was slightly lower than in controls; no differences were found in the other clinical/demographic variables evaluated. A total of 273 patients entered long term follow-up (mean, 52 months). Proximal extension of the disease occurred in 74 of them (27.1%). The cumulative rate of proximal extension and of extension beyond the splenic flexure was 20% and 4% at 5 yr and 54% and 10% at 10 yr, respectively. The risk of proximal extension was higher in nonsmokers, in patients with >3 relapses/yr, and in patients needing systemic steroid or immunosuppressive treatment. Refractory disease was confirmed as an independent prognostic factor at multivariate analysis. CONCLUSIONS: Proximal extension of ulcerative proctitis is frequent and may occur even late after the original diagnosis. However, the risk of extension beyond the splenic flexure appears to be quite low. Smoking seems to be a protective factor against proximal extension, whereas refractoriness is a risk factor for proximal extension of the disease.

Adolescent↗
PubMed2000

Impaired translational response and increased protein kinase PKR expression in T cells from lupus patients.

Activation of peripheral blood T cells results in a rapid and substantial rise in translation rates and proliferation, but proliferation in response to mitogen stimulation is impaired in systemic lupus erythematosus (SLE). We have investigated translation rates and initiation factor activities in T cells from SLE patients in response to activating signals. Activation by PMA plus ionomycin strongly increased protein synthesis in control T cells but not in T cells from SLE patients. The rate of protein synthesis is known to be strongly dependent on the activity of two eukaryotic translation initiation factors, eIF4E and eIF2alpha. We show that following stimulation, eIF4E expression and phosphorylation increased equivalently in control and SLE T cells. Expression of eIF4E interacting proteins - eIF4G, an inducer, and 4E-BP1 and 4E-BP2, two specific repressors of eIF4E function - and the phosphorylation level of 4E-BP1, were all identical in control and SLE T cells. In contrast, the protein kinase PKR, which is responsible for the phosphorylation and consequent inhibition of eIF2alpha activity, was specifically overexpressed in activated SLE T cells, correlating with an increase in eIF2alpha phosphorylation. Therefore, high expression of PKR and subsequent eIF2alpha phosphorylation is likely responsible, at least in part, for impaired translational and proliferative responses to mitogens in T cells from SLE patients.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Guidelines for the treatment of adults with severe head trauma (part I). Initial assessment; evaluation and pre-hospital treatment; current criteria for hospital admission; systemic and cerebral monitoring.

If pragmatic recommendations for treatment of severely head-injured patients could really be applied, they would probably have a considerable impact in terms of reduction in mortality and disability. Since 1995 a Group of Italian Neurointensivists and Neurosurgeons belonging to the Italian Societies of Neurosurgery (SINch) and Anesthesiology & Intensive Care (SIAARTI) has produced this first part of recommendations that are completed by Medical treatment (Part II) and Surgical treatment criteria (Part III). These recommendations reflect a multidisciplinary consent but are based on scientific evidence, when available, and take origin mainly from expert opinions and the current clinical and organizational situation. For this aspect they differ from other American and European guidelines, which are strictly based on criteria of proven efficacy. These recommendations aim at providing a practical reference for all those dealing with severe head injuries from first-aid to intensive care units, setting out the minimal goals of management to be reached throughout the country. For these reasons they need continual critical review and updating. Main clinical aims are: 1) to prevent secondary cerebral damage by continuous and meticulous maintenance of systemic homeostasis 2) to standardize methods of neurological evaluation and CT scan classification and scheduling; 3) to give simple indications for systemic and cerebral monitoring 4) to pragmatically discuss the organizational scenarios and specify the minimal safe clinical approach when patients are treated in non-specialized settings. Briefly, smooth tracheal intubation and ventilation in all comatose patients, administration of rapidly metabolized sedative and analgesic drugs to permit frequent neurological evaluation, restoration of volemia and systolic blood pressure above 110 mm Hg, oxygen saturation >95% and normocapnia, are all recommended from the very early treatment and transport. Homogeneity of language, reliable and correctly tested Glasgow Coma Score and pupillary reflexes, and a simple CT scan classification are recommended to improve communications and clinical decisions in the multidisciplinary setting of management. In comatose patients, cerebral perfusion pressure, intracranial pressure and oxygen jugular saturation must be monitored according to specific criteria, which are described. Therapy with hyperventilation and mannitol should be used only in case of clinical deterioration and uncal herniation. This therapy could be useful to gain time to reach neurosurgery. The aim of these recommendations is to achieve safer management of severely brain injured patients, immediate diagnosis of clinical deterioration and successful identification and treatment of surgical lesions. The impact of these guidelines requires further verification.

Adult↗
PubMed2000

Guidelines for the treatment of adults with severe head trauma (part II). Criteria for medical treatment.

Since 1995 a Group of Italian Neurointensivists and Neurosurgeons belonging to the Italian Societies of Neurosurgery (SINch) and Anesthesia & Intensive Care (SIAARTI) has produced some recommendations for treatment of adults with severe head trauma. They have been published in 3 parts: Part I (Initial assessment, Evaluation and pre-hospital treatment, Criteria for hospital admission, Systemic and cerebral monitoring), Part II (Medical treatment) and Part III (Surgical treatment criteria). These recommendations reflect a multidisciplinary consent and are mostly based on expert opinion. The main aim is to provide a practical reference for all those dealing with severe head injuries from first-aid to intensive care units, setting out the minimal goals of management to be reached throughout the Country. These recommendations need a continuous critical review and updating. Medical treatment is aimed at preventing or minimizing secondary brain damage following acute brain injury, provided that surgical masses have been promptly identified and removed. In order to assure cerebral perfusion, systemic hemodynamics and respiratory exchanges should be normal. Volemia is crucial, and mean arterial pressure should remain above 90 mmHg. Good general intensive care, including gastroprotection, water-electrolyte balance, infection control, nutrition and physiotherapy, is assumed as the basis for brain-oriented therapy. Intracranial hypertension requires an approach based on various steps. First, factors that can directly rise intracranial pressure (ICP) such as venous outflow obstruction, fever, pain etc. should be checked and corrected. Second, Mannitol, CSF withdrawal, sedation and moderate hyperventilation should be applied. This can be done by targeting specific problems with specific treatment (which is possible when the cause of ICP rise is known) or in a step-wise approach, by using less aggressive interventions before than more aggressive ones, with a higher risk of complications. Third, extreme treatment, such as barbiturates, should be reserved to cases with refractory intracranial hypertension. The main goal of ICP treatment is not simply ICP reduction, but the maintenance of adequate cerebral perfusion pressure.

Adult↗
PubMed2000

Guidelines for the treatment of adults with severe head trauma (part III). Criteria for surgical treatment.

The Guidelines of the surgical management of severe head injury in adults, as evolved by the Neurotraumatology Group of the Italian Neurosurgery Society and the Italian Society for Anaesthesia, Analgesia, Reanimation and Intensive Care are presented and briefly discussed. Guidelines presented here are of a pragmatic nature, based on consensus and expert opinion. Aspects pertaining to specific indications to surgery and/or to the possibility of conservative management of different traumatic intracranial lesions are highlighted. The importance of surgery in preventing secondary insults to the traumatised brain is emphasised.

Adult↗