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Biomedical subjects

M Ceppi

Publications and source records attributed to M Ceppi.

At least 19 recordsLinked to original sources
PubMed2005

[Pulmonary infiltrates and peripheral blood eosinophilia].

A 43-year-old asthmatic woman was hospitalised because of fever, cough, expectorations and asthenia. Chest X-rays showed bilateral pulmonary infiltrates. Peripheral blood eosinophilia was greater than 9 G/l. Bronchoalveolar lavage revealed a massive eosinophilia. The clinical features were consistent with a chronic eosinophilic pneumonia. All the symptoms resolved with the initiation of prednisone treatment. The differential diagnosis of eosinophilic pneumonia is discussed.

Adrenal Cortex Hormones↗
PubMed2005

Double-stranded secondary structures on mRNA induce type I interferon (IFN alpha/beta) production and maturation of mRNA-transfected monocyte-derived dendritic cells.

BACKGROUND: The development of dendritic cell (DC)-based vaccines using antigen-encoding mRNA requires identification of the critical parameters for efficient ex vivo loading of DCs. Exogenously delivered mRNA can induce DC activation, but the molecular mechanisms involved are unknown. The aim of the present study was to identify the means by which mRNA-dependent activation of DCs occurs. METHODS: In vitro transcribed mRNA molecules were delivered into porcine monocyte-derived DCs (MoDCs) using different non-viral gene transfer procedures. Using the green fluorescent protein (GFP) as reporter gene, as well as rhodamine-labeled RNA, intracellular delivery and transfection efficiency were assessed by confocal microscopy and flow cytometry. DC activation was monitored in terms of MHC class II and CD80/86 upregulation, as well as the production of type I interferon (IFN-alpha/beta). RESULTS: mRNA-lipofected MoDCs produced type I IFN and upregulated MHC class II and CD80/86. Computational analysis of the mRNA molecules predicted highly ordered secondary structures forming double-stranded RNA (dsRNA). This dsRNA was also detectable by immunofluorescence in mRNA-lipofected cells, using antibody specific for dsRNA. Digestion of the mRNA prior to lipofection with a double-strand-specific RNase, but not a single-strand-specific RNase, abrogated DC activation. Impairment of protein kinase R (PKR) with 2-aminopurine also interfered with the activation. CONCLUSIONS: Double-stranded secondary structures on mRNA delivered by lipofection can activate MoDCs. This could have important implications for mRNA-based immunomodulation of DCs, DC-based immunotherapy, and formulation of RNA-based vaccines. In addition, this report describes the first in vitro steps towards development of a novel large animal model system to evaluate DC-based vaccines against infectious diseases.

Animals↗
PubMed2005

Identification of classical swine fever virus protein E2 as a target for cytotoxic T cells by using mRNA-transfected antigen-presenting cells.

Vaccination of pigs against Classical swine fever virus (CSFV) by using live-virus vaccines induces early protection before detectable humoral immune responses. Immunological analyses indicate that this is associated with T-cell activation, underlining the importance of targeting cytotoxic T-lymphocyte (CTL) responses for vaccine improvement. Antigen-presenting cells (APCs) transfected with mRNA encoding structural protein E2 or non-structural viral proteins NS3-NS4A were used to identify viral genes encoding CTL epitopes. Monocyte-derived dendritic cells (DCs) and fibrocytes served as the APCs. In vitro translation of the mRNA and microscopic analysis of transfected cells demonstrated that E2 and NS3-NS4A could be identified. APCs transfected with either of the mRNA molecules restimulated CSFV-specific T cells to produce gamma interferon and specific cytotoxic activity against CSFV-infected target cells. The presence of CTL epitopes on E2 was confirmed by using d/d-haplotype MAX cells expressing E2 constitutively as target cells in d/d-haplotype CTL assays. A potent CTL activity against E2 was detected early (1-3 weeks) after CSFV challenge. This work corroborates the existence of CTL epitopes within the non-structural protein domain NS3-NS4A of CSFV. Furthermore, epitopes on the E2 protein can also now be classified as targets for CTLs, having important implications for vaccine design, especially subunit vaccines. As for the use of mRNA-transfected APCs, this represents a simple and efficient method to identify viral genes encoding CTL epitopes in outbred populations.

Animals↗
PubMed2004

Interaction of classical swine fever virus with dendritic cells.

Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte- and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-alpha/TNF-alpha or polyinosinic-polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN-alpha responses in these DCs and even suppressed pIC-induced IFN-alpha induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF-alpha were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation.

Animals↗
PubMed2004

A mortality cohort study among workers in a graphite electrode production plant in Italy.

BACKGROUND: Graphite electrode manufacturing workers are exposed to coal tar and its volatiles containing a variety of polycyclic aromatic hydrocarbons (PAH), silica and graphite dusts, and asbestos. AIMS: To investigate mortality from cancer and other diseases among workers in a graphite electrode production plant in Italy. METHODS: A total of 1291 males actively employed between 1 January 1950 and 31 December 1989 who had worked at the plant for at least one year were studied. The follow up extended from 1950 to 1997. Standardised mortality ratios (SMR) and their 95% confidence intervals (CI) were computed using mortality rates for the Italian and regional male population. RESULTS: Excess mortality was observed for all causes (SMR 1.44, CI 1.32 to 1.56), all cancers (SMR 1.27, CI 1.07 to 1.50), liver cancer (SMR 4.19, CI 2.68 to 6.23), silicosis (SMR 66.39, CI 52.56 to 82.7), and cirrhosis and other chronic diseases of the liver (SMR 1.87, CI 1.31 to 2.59) in comparison with the national male population. When regional rates were used to calculate the number of expected deaths, SMRs remained higher for silicosis (SMR 57.32, 42.11 to 76.22), and liver cancer (SMR 2.57, 1.57 to 3.97). Mortality from silicosis was increased in workers hired at young ages (<25 years, SMR 81.79; 25-34 years, SMR 82.73), and in workers aged <45 at death (SMR 333.3, CI 159.8 to 613). Mortality from liver cancer increased threefold (SMR 3.11, CI 1.78 to 5.05) in workers with more than 10 years of employment at the plant during the manufacture of Karbate products. CONCLUSIONS: Results support the association between excess mortality from silicosis and occupational exposure to siliceous sands experienced during graphite electrode manufacturing. The observed excess mortality from liver cancer is compatible, to some extent, with exposures that may have occurred during the manufacture of phenolic and furfuryl resins treated products, although a role of lifestyle factors and viral infections cannot be excluded.

Adult↗
PubMed2001

Occupational exposure to carbon black and risk of bladder cancer.

Exposure to carbon black has been linked to risk of lung and bladder cancer. We therefore investigated the frequency of these cancers in a group of 2286 longshoremen who were exposed occupationally to carbon-black dust. We identified 208 cancers (standardised incidence ratio 96, 95% CI 83-109), 53 lung cancers (108, 81-141), and 32 bladder cancers (130, 89-184). Longshoremen exposed to high concentrations of carbon black (n=14) had a significantly increased frequency of bladder cancer (204, 112-343). We conclude that the increase in bladder cancer in longshoremen is probably related to high exposure to carbon black.

Adult↗
PubMed2001

Analysis of 13 (32)P-DNA postlabeling studies on occupational cohorts exposed to air pollution.

Industrial and urban workers may be exposed to significant levels of air pollutants resulting from the incomplete combustion of organic matter. The authors performed a meta-analysis of 13 DNA-adduct studies ((32)P-DNA postlabeling technique) on occupational cohorts exposed to air pollution. The association between levels of DNA adducts and air pollution exposure was significant both in heavily exposed industrial workers and in less severely exposed urban workers. Moreover, in an analysis using the seven studies that reported measuring levels of benzo[a]pyrene (B(a)P), a typical marker of exposure, DNA adduct levels in exposed workers (versus those in referents) were significantly correlated with air levels of B(a)P. The relation between DNA adducts and B(a)P was found to be linear at low doses and sublinear at high doses, indicating that DNA adduct formation tends to reach some kind of saturation point at higher levels of exposure to the chemical mixtures present in fumes. When the authors examined the efficiency of DNA adduct production associated with increasing air pollution exposures, the production of DNA adducts per unit of exposure was significantly decreased at higher B(a)P exposure levels. These findings suggest that linear downward extrapolations based on DNA adduct levels associated with B(a)P concentrations of > or =20 ng/m(3) might be affected by underestimation bias.

Air Pollutants, Occupational↗
PubMed2001

A historical cohort mortality study among shipyard workers in Genoa, Italy.

BACKGROUND: A historical cohort mortality study was conducted among 3984 shipyard workers assigned to ship repair, refitting, and construction in the harbor of Genoa, Italy, between 1960 and 1981. These workers were exposed to asbestos fibers, welding fumes and gases, silica dust, polycyclic aromatic hydrocarbons, and solvents. METHODS: Workers were classified in 20 different job-titles depending upon the type of activity. Standardized mortality ratios (SMRs) were computed using male residents of the Province of Genoa as the referent population. RESULTS AND CONCLUSIONS: For the whole cohort significantly increased SMRs were detected for all causes, all cancers, liver, larynx, lung, pleural and bladder cancers, respiratory tract diseases, and cirrhosis of the liver. The analysis by job-title showed increased SMRs not only for pleural cancer, but also for lung, laryngeal cancers and respiratory tract diseases in occupations entailing heavy asbestos exposure. Bladder and liver cancers and liver cirrhosis mortality also appeared to be related to occupational exposure.

Adult↗
PubMed2001

Selective enhancement of gene transfer by steroid-mediated gene delivery.

The incorporation of transgenes into the host cells' nuclei is problematic using conventional nonviral gene delivery technologies. Here we describe a strategy called steroid-mediated gene delivery (SMGD), which uses steroid receptors as shuttles to facilitate the uptake of transfected DNA into the nucleus. We use glucocorticoid receptors (GRs) as a model system with which to test the principle of SMGD. To this end, we synthesized and tested several bifunctional steroid derivatives, finally focusing on a compound named DR9NP, consisting of a dexamethasone backbone linked to a psoralen moiety using a nine-atom chemical spacer. DR9NP binds to the GR in either its free or DNA-crosslinked form, inducing the translocation of the GR to the nucleus. The expression of transfected DR9NP-decorated reporter plasmids is enhanced in dividing cells: expression of steroid-decorated reporter plasmids depends on the presence of the GR, is independent of the transactivation potential of the GR, and correlates with enhanced nuclear accumulation of the transgene in GR-positive cells. The SMGD effect is also observed in cells naturally expressing GRs and is significantly increased in nondividing cell cultures. We propose that SMGD could be used as a platform for selective targeting of transgenes in nonviral somatic gene transfer.

Active Transport, Cell Nucleus↗
PubMed2001

HUman MicroNucleus project: international database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei.

Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5 per thousand and the interquartile range was between 3 and 12 per thousand. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods.

Adolescent↗
PubMed2000

Mesothelioma and lung tumors attributable to asbestos among petroleum workers.

BACKGROUND: Asbestos exposure has been definitively found to be associated with both mesothelioma and lung cancer. Nevertheless, in the overall population of oil refinery workers potentially exposed to asbestos, many studies clearly show a definitely increased risk of mesothelioma, but no proven excess of lung cancer after comparison to the general population. Through the presentation of new data and the re-appraisal of two recent and independent epidemiological studies conducted in Liguria, Italy, and Ontario, Canada, we attempt to shed light on this apparently paradoxical finding. METHODS: Lung cancer mortality was studied among maintenance workers exposed to asbestos, and among two other subgroups of refinery employees: blue collar and white collar workers. The comparison with blue collar workers was performed in order to take into account the role of healthy worker effect, smoking habit, and the socioeconomic level. The comparison with white collar workers was performed to control for other occupational lung carcinogens. RESULTS AND CONCLUSIONS: Results reveal a consistency between the two studies and show that 96-100% of the mesotheliomas and 42-49% of the lung tumors arising among maintenance workers were attributable to asbestos exposure. Our new analysis, estimating two cases of asbestos-related lung cancer for each case of mesothelioma, confirms published findings on the magnitude of asbestos-related tumors in oil refineries.

Asbestos↗
PubMed1999

Analysis of correlated data in human biomonitoring studies. The case of high sister chromatid exchange frequency cells.

Sister chromatid exchange (SCE) analysis in peripheral blood lymphocytes is a well established technique that aims to evaluate human exposure to toxic agents. The individual mean value of SCE per cell had been the only recommended index to measure the extent of this cytogenetic damage until the early 1980's, when the concept of high frequency cells (HFC) was introduced to increase the sensitivity of the assay. All statistical analyses proposed thus far to handle these data are based on measures which refer to the individual mean values and not to the single cell. Although this approach allows the use of simple statistical methods, part of the information provided by the distribution of SCE per single cell within the individual is lost. Using the appropriate methods developed for the analysis of correlated data, it is possible to exploit all the available information. In particular, the use of random-effects models seems to be very promising for the analysis of clustered binary data such as HFC. Logistic normal random-effects models, which allow modelling of the correlation among cells within individuals, have been applied to data from a large study population to highlight the advantages of using this methodology in human biomonitoring studies. The inclusion of random-effects terms in a regression model could explain a significant amount of variability, and accordingly change point and/or interval estimates of the corresponding coefficients. Examples of coefficients that change across different regression models and their interpretation are discussed in detail. One model that seems particularly appropriate is the random intercepts and random slopes model.

Adult↗
PubMed1998

[Carbamazepine-induced agranulocytosis. Apropos of 2 cases].

Carbamazepine-induced agranulocytosis (CIA) is a rare event. We report on two cases, highlighting the wide variability of the bone marrow, which may show pseudohypercellularity with disappearance of neutrophils and excess of immature cells (myeloblasts and promyelocytes), thus mimicking the features of acute myeloid leukemia. Although its pathogenesis is still unclear, CIA must be considered as an idiosyncratic hemopathy and moreover it appears to be an unpredictable complication among patients taking the drug. It should be clearly distinguished from the benign neutropenia frequently associated with carbamazepine therapy and often self-limiting. Anyhow a careful clinical and hematological monitoring is the only mean to recognize promptly this life-threatening disease and to treat it with the withdrawal of the drug and the administration of an adequate anti-infectious therapy.

Aged↗
PubMed1997

Mortality in a cohort of tannery workers.

OBJECTIVES: To evaluate the mortality of a group of tannery workers. METHODS: The cohort consisted of 1244 workers (870 men and 374 women) employed at a chrome tannery between 1955 and 1988. A total of 36414 person-years of follow up was calculated (369 people had died). National and regional mortalities were used to estimate the expected numbers. RESULTS: All cause mortality was similar to that of the general population. The most remarkable excess was for bladder cancer (observed 10, standardised mortality ratio (SMR) 242, 95% confidence interval (95% CI) 116 to 446). An excess of colorectal cancer (observed 17, SMR 180, 95% CI 105 to 288) was also found, based on an increased risk of both colon (SMR 166) and rectal cancer (SMR 206). No recognisable patterns emerged from the analyses by years since first employment, calendar year of hire, or lagging exposures. CONCLUSIONS: The increased mortality from bladder cancer is likely due to exposure to benzidine based leather dyes. If the apparent excess of colorectal cancer is real, its causes are as yet unknown.

Adolescent↗
PubMed1996

[Primary thrombocythemia in a female carrier of IgA deficiency].

We describe a case of essential thrombocythemia observed in a 67-year-old woman with severe IgA-deficiency. The the best of our knowledge, this is the first report concerning the onset of a chronic myeloproliferative disease (CMPD) in a patient affected with primary immunodeficiency, in particular IgA-defect. The association may be merely coincidental; otherwise hemopoietic growth factors acting on myeloid progenitor cells could play a role in this relationship. It has recently been shown that serum levels of many cytokines are elevated in patients with CMPD and probably contribute to enhance proliferation of the malignant clones; on the other hand interleukin-6 seems to account for reactive thrombocytosis, and significant amounts of circulating interleukin-4 and interleukin-6 have been detected in IgA-deficient patients. Overproduction of the two cytokines may depend on recurrent infections, but it could also represent a primary abnormality, with a putative role in the pathogenesis of the immune defect. These findings suggest that high levels of growth factors could induce myeloid hyperproliferation and so expose stem cells to genetic mutations responsible for malignant transformation.

Aged↗
PubMed1995

The mortality rate of the province of birth as a risk indicator for lung and stomach cancer mortality among Genoa residents born in other Italian provinces.

This study analyses the relationship between migration and mortality for lung and stomach cancer, these diseases being those considered susceptible to changes in environmental conditions and individual habits that usually follow migration. Mortality rate of the province of birth was used as the index of risk related to migration. Data were analysed using the Poisson regression model for grouped data. Results indicate that migration determines modifications in the mortality rates of the migrant populations for the diseases under study. For lung cancer, the analysis showed a greater risk for migrants originating from areas with high rates and that migrants had a reduced risk in comparison with natives of Genoa. With regard to stomach cancer, the study revealed that migrants originating from high risk areas had higher relative risks than the Genoa natives, even if these were lower than expected when compared to the risks of the populations in the regions from which the migrants originated.

Emigration and Immigration↗