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Biomedical subjects

Fabrizio Bianchi

Publications and source records attributed to Fabrizio Bianchi.

At least 19 recordsLinked to original sources
PubMed2006

No evidence of chromosome damage in chronic obstructive pulmonary disease (COPD).

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. It is characterized by a progressive airflow limitation resulting from an abnormal inflammatory response of the lungs to inhaled gases and particles. Since oxidative stress is thought to play a role in COPD, and since increased oxidative stress is associated with chromosomal instability in several diseases, we investigated whether such relationship also exists in COPD. Whole blood lymphocytes from 49 COPD patients and 48 age- and sex-matched controls were cultivated in vitro and cytogenetic damage was evaluated by micronucleus (MN) and sister-chromatid-exchange (SCE) assays. In patients with COPD, MN frequency was not significantly different from that of controls. Similarly, SCE frequency did not differ in the two groups suggesting no disturbance in DNA replication. Unlike other diseases characterized by oxidative stress, COPD does not appear to be associated with DNA damage.

Aged↗
PubMed2006

Cancer mortality in an area of Campania (Italy) characterized by multiple toxic dumping sites.

Several recent studies have documented that a widespread practice of dumping toxic wastes has taken place for many years in the Provinces of Naples and Caserta. Extensive programs of environmental monitoring are currently ongoing in the area. In this frame, the Department of Civil Defence of the Italian Government has appointed an ad hoc study group in order to assess the health status of the population resident in the area of interest. The first investigation performed by the study group has been a geographic study on cancer mortality and occurrence of malformations in 196 municipalities constituting the two Provinces. The study detected an area located in the southeastern part of the Province of Caserta and in the northwestern part of the Province of Naples, where cancer mortality and congenital malformations show significantly increased rates with respect to expected figures derived from the regional population. The area highlighted by the study is, in general terms, overlapping with the area where most illegal dumping of toxic wastes took place. It is now recommended that mortality studies be extended to take into account other health outcomes, to search for correlations with environmental exposures, and consider possible confounding factors.

Cohort Studies↗
PubMed2005

Inflammatory markers and serum lipids in idiopathic dilated cardiomyopathy.

Coronary microcirculation is impaired in idiopathic dilated cardiomyopathy (IDC), possibly because of endothelial dysfunction. High-density lipoproteins (HDLs) have the potential to regulate endothelial function and modulate inflammation and the innate immune response. This study investigated whether reduced HDLs, concomitantly with the activation of inflammation, are associated with IDC. Fifty-five patients with IDC, without evidence of other organ or systemic, chronic, or recurrent diseases, were compared with 55 healthy controls for HDLs and complete lipid profiles, C-reactive protein, C3 and C4 complement fractions, soluble intercellular adhesion molecule-1 and soluble endothelial leukocyte adhesion molecule-1, haptoglobin, and ceruloplasmin. Patients with IDC differed from controls, with lower HDL levels, lower apolipoprotein A-I and A-II levels, and higher triglyceride levels, but not on total and low-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein(a). In addition, all measured inflammation markers were significantly greater in patients with IDC than in controls and were negatively correlated with HDLs. A strong and independent association with IDC was found for age, soluble intercellular adhesion molecule-1, and HDLs that, when categorized as <40 or >40 mg/dl, showed the strongest association (prevalence odds ratio 0.10, p <0.0005) with the disease. In conclusion, the data here reported on reduced HDLs and increased endothelial inflammatory activation and the linear negative correlation between HDLs and inflammation markers, particularly soluble intercellular adhesion molecule-1, could suggest a role for HDLs in the endothelial-microvascular dysfunction seen in IDC.

Adult↗
PubMed2005

A cancer-specific transcriptional signature in human neoplasia.

The molecular anatomy of cancer cells is being explored through unbiased approaches aimed at the identification of cancer-specific transcriptional signatures. An alternative biased approach is exploitation of molecular tools capable of inducing cellular transformation. Transcriptional signatures thus identified can be readily validated in real cancers and more easily reverse-engineered into signaling pathways, given preexisting molecular knowledge. We exploited the ability of the adenovirus early region 1 A protein (E1A) oncogene to force the reentry into the cell cycle of terminally differentiated cells in order to identify and characterize genes whose expression is upregulated in this process. A subset of these genes was activated through a retinoblastoma protein/E2 viral promoter required factor-independent (pRb/E2F-independent) mechanism and was overexpressed in a fraction of human cancers. Furthermore, this overexpression correlated with tumor progression in colon cancer, and 2 of these genes predicted unfavorable prognosis in breast cancer. A proof of principle biological validation was performed on one of the genes of the signature, skeletal muscle cell reentry-induced (SKIN) gene, a previously undescribed gene. SKIN was found overexpressed in some primary tumors and tumor cell lines and was amplified in a fraction of colon adenocarcinomas. Furthermore, knockdown of SKIN caused selective growth suppression in overexpressing tumor cell lines but not in tumor lines expressing physiological levels of the transcript. Thus, SKIN is a candidate oncogene in human cancer.

Adenovirus E1A Proteins↗
PubMed2005

Cystathionine beta-synthase c.844ins68 gene variant and non-syndromic cleft lip and palate.

Non-syndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with substantial clinical and social impact and whose causes include both genetic and environmental factors. Folate and homocysteine (Hcy) metabolism have been indicated to play a role in the etiology of CL/P, and polymorphisms in folate and Hcy genes may act as susceptibility factors. We investigated a common polymorphism in the cystathionine beta-synthase (CBS) gene (c.844ins68) in 134 Italian CL/P cases and their parents using the transmission disequilibrium test (TDT). Although no overall linkage disequilibrium was observed, considering the parent-of-origin transmission of the CBS 68 bp insertion a significant (P = 0.002) transmission distortion was detected. When children receive the c.844ins68 allele from the mother compared to the father, they show a 18.7-fold increase in risk for CL/P. This evidence suggests CBS as a candidate gene for CL/P and supports a role of maternal-embryo interactions in the etiology of CL/P.

Alleles↗
PubMed2005

Sex and congenital malformations: an international perspective.

The study evaluated the sex distribution of major isolated malformations and common trisomies among a large and geographically varied sample. Eighteen registries from 24 countries contributed cases, which were centrally reviewed and classified in three clinical types as isolated, associated, or syndromic. We selected cases of 26 major defects (n = 108,534); trisomy 21, 18, and 13 (n = 30,114); other syndromes (n = 2,898); and multiple congenital anomalies (n = 24,197), for a total of 165,743 cases. We observed a significant deviation of sex distribution (compared to a sex ratio of 1.06 or male proportion of 51.4%) for 24 of the 29 groups (a male excess in 16, a female excess in 8), and in 8 of such groups these estimates varied significantly across registries. A male excess was noted for two left obstructive cardiac defects (hypoplastic left heart and coarctation of the aorta) and a female excess for all the main types of neural tube defects. A male excess was seen for omphalocele but not gastroschisis. For neural tube defects the female excess tended to be stronger in areas with historically high prevalence for these defects. For 15 of the 26 birth defects the sex distribution differed among isolated, associated, and syndromic cases. Some of these epidemiologic commonalities are consistent with known or putative developmental processes. Further, the geographic variation for some defects may reflect local prevalence rates and risk factors. Finally, the findings underscore the need for clinical classification (e.g., into isolated, multiple, syndromes) in studies of birth defects.

Abnormalities, Multiple↗
PubMed2005

Gene expression signature for angiogenic and nonangiogenic non-small-cell lung cancer.

Angiogenesis is regarded as essential for tumour growth. However, we have demonstrated that some other aggressive non-small-cell lung carcinomas (n-SCLC) do not have angiogenesis. In this study, using cDNA microarray analysis, we demonstrate that angiogenic and nonangiogenic tumour types can be distinguished by their gene expression profiles. Tissue samples from 42 n-SCLC patients were obtained with consent. In all, 12 tumours were nonangiogenic and 30 angiogenic. The two groups were matched by age, sex, smoking and tumour stage. Total RNAs were extracted followed by microarray hybridization and image scan procedure. Data were analysed using GeneSpring 5.1 software. A total of 62 genes were found to be able to separate angiogenic from nonangiogenic tumours. Nonangiogenic tumours have higher levels of genes concerned with mitochondrial metabolism, mRNA transcription, protein synthesis and the cell cycle. Angiogenic tumours have higher levels of genes coding for membrane vesicles, integrins, remodelling, angiogenesis and apoptosis. These results further support our first finding that nonangiogenic lung tumours are fast-growing tumours filling the alveoli in the absence of vascular remodelling. We raise the hypothesis that in nonangiogenic tumours, hypoxia leads to a higher activation of the mitochondrial respiratory chain, which allows tumour growth without triggering angiogenesis.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Distinct molecular signature of inflammatory breast cancer by cDNA microarray analysis.

Inflammatory breast cancer (IBC) is a clinically distinct and aggressive form of locally advanced breast cancer with largely unknown genetic determinants. Overexpression of the RhoC GTPase and of HER2, and decreased ER-expression are involved in IBC. Multimodality treatment has increased survival but prognosis is still poor. Novel molecular targets for improved neoadjuvant treatment are necessary. Using cDNA microarrays, we performed genome-wide expression profiling of pre-treatment tumour samples of 16 patients with IBC and 18 patients with non-stage-matched non-IBC. Rigid clinical diagnostic criteria according to the TNM classification of the American Joint Committee on Cancer were adopted. Unsupervised hierarchical clustering accurately distinguished IBC and non-IBC samples. A set of 50 discriminator genes was identified in a learning group of tumour samples and was successful in diagnosing IBC in a validation group of samples (accuracy of 88%). Exclusion of ER-related or HER2-related genes did not alter this discriminatory accuracy, indicating that the expression of other genes in addition to ER and HER2 characterize the IBC phenotype. The molecular signature of IBC revealed the overexpression of a large number of NF-kappaB target genes, explaining at least part of the aggressive nature of IBC. Successful validation of some of the overexpressed genes by immunohistochemistry or real-time quantitative PCR demonstrated the robustness of the cDNA microarray experiments. The results of our study provide potential targets for the treatment of patients with IBC.

Belgium↗
PubMed2004

Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.

PURPOSE: Spiral computed tomography (CT) can detect lung cancer at an early stage, but the malignant potential is unknown. The question is, as follows: do these small lesions have the same lethal potential as do symptomatic tumors? EXPERIMENTAL DESIGN: We used a cDNA microarray platform and compared the gene expression profile of spiral CT-detected lung carcinomas with a matched case-control population of patients presenting with symptomatic lung cancer. RESULTS: CT-detected and symptomatic tumors have shown a comparable gene expression profile. Correspondence analysis has demonstrated that nine genes were differentially expressed, although with a high variability across the samples that prevented distinguishing the two groups of tumors. Analysis of these nine genes has suggested that early-detected tumors have higher levels of retinoic acid production and higher expression levels of caveolin 2, matrix Gla, and cystatin A, which are already known to be lost during tumor progression. CONCLUSIONS: All of the tumors observed are histologically malignant according to the WHO Classification. Early lung cancers that are detected by screening have a gene expression pattern similar to, but not identical to, that of symptomatic lung carcinomas.

Aged↗
PubMed2004

Epidemiology of cleft palate in Europe: implications for genetic research.

OBJECTIVE: To describe the epidemiology of cleft palate (CP) in Europe. DESIGN AND SETTING: A descriptive epidemiological study on 3852 cases of CP, identified (1980 through 1996) from more than 6 million births from the EUROCAT network of 30 registers in 16 European countries. RESULTS: Significant differences in prevalence in Europe between registries and within countries were observed. A total of 2112 (54.8%) CP cases occurred as isolated, 694 (18.0%) were associated with other defects such as multiple congenital anomalies, and 1046 (27.2%) were in recognized conditions. The study confirmed the tendency toward female prevalence (sex ratio [SR] = 0.83), particularly among isolated cases (SR = 0.78) even if SR inversion is reported in some registries. A specific association with neural tube defects (NTDs) in some registers is reported. CONCLUSION: The differences identified in Europe (prevalence, sex, associated anomalies) can be only partially explained by methodological reasons because a common methodology was shared among all registries for case ascertainment and collection, and CP is an easy detectable condition with few induced abortions. The complex model of inheritance and the frequently conflicting results in different populations on the role of genes that constitute risk factors suggest the presence of real biological differences. The association of CP/NTD in an area with a high prevalence of NTDs can identify a group of conditions that can be considered etiologically homogeneous. The epidemiological evaluation can guide genetic research to specify the role of etiological factors in each different population

Abnormalities, Multiple↗
PubMed2004

Health effects of exposure to waste incinerator emissions:a review of epidemiological studies.

This review evaluates the epidemiological literature on health effects in relation to incineration facilities. Several adverse health effects have been reported. Significant exposure-disease associations are reported by two thirds of the papers focusing on cancer (lung and larynx cancer, non-Hodgkin's lymphoma). Positive associations were found for congenital malformations and residence near incinerators. Exposure to PCB and heavy metals were associated with several health outcomes and in particular with reduction of thyroid hormones. Findings on non-carcinogen pathologies are inconclusive. Effect of biases and confounding factors must be considered in the explanation of findings. Methodological problems and insufficient exposure information generate difficulties on study results. Research needs include a better definition of exposure in qualitative and quantitative terms in particular by developing the use of biomarkers and by implementing environmental measurements.

Carcinogens↗
PubMed2004

[Prognostic value of high-density lipoproteins in the cardiology unit].

BACKGROUND: Clinical and epidemiological studies have shown an inverse and independent association between high-density lipoproteins (HDL) and risk of developing coronary artery disease. The aim of this study was to estimate the prevalence of the phenotype characterized by low HDL values and to assess the impact of HDL plasma levels on the prognosis of patients hospitalized in the cardiologic unit of our Institute, during 30 months of follow-up. METHODS: Between February 1999 and February 2002, 1169 patients (778 men and 391 women) who had undergone hospitalization, were enrolled in a cardiovascular registry. The lipid profile was evaluated for all patients; a subgroup (n = 626) underwent coronary angiography. Patients were followed up for a mean period of 30 months, during which the frequency of revascularization procedures (coronary angioplasty or bypass), myocardial infarction and death were recorded. RESULTS: Nearly half of the subjects (45%, of which 77% men) showed HDL values < 40 mg/dl, and 25% of the population (80% men) were characterized by extremely reduced HDL concentrations (< or = 35 mg/dl). Patients with coronary atherosclerosis showed HDL levels lower than those of subjects with negative angiography (41.0 +/- 10.8 vs 46.6 +/- 10.9 mg/dl, p < 0.0005). An inverse relationship was found between HDL and coronary artery disease: the risk of developing the illness decreased by 4% for each increase of 1 mg/dl in HDL (p < 0.005); in males < 60 years and females < 65 years, the coronary artery disease risk association increased by 3% (p < 0.005). The risk of interventions decreased by 2% for each increase of 1 mg/dl in HDL (p < 0.01), both in the total population and in males < 60 years and females < 65 years. Finally, patients with HDL < 40 mg/dl showed a higher risk of revascularization interventions (+25%, p < 0.01) in comparison to the subjects with HDL > 40 mg/dl. CONCLUSIONS: This study demonstrates: a) the high prevalence of the phenotype characterized by low plasma concentrations of HDL among patients hospitalized in a cardiologic unit; b) lower HDL values in subjects with coronary atherosclerosis compared to subjects with normal coronary angiography; c) the inverse relationship between HDL and coronary atherosclerosis; d) the prognostic value of HDL as a predictor of surgical revascularization.

Adolescent↗
PubMed2002

Regulation of ADL6 activity by its associated molecular network.

Plant dynamin-like proteins consist of a group of high molecular weight GTPase with diverse structural arrangements and cellular localizations. In addition, unlike animal dynamins, there was no evidence for the involvement of any plant dynamin-like protein in clathrin-mediated vesicle trafficking. In this study we demonstrate that ADL6 (Arabidopsis dynamin-like protein 6), due to its domain arrangement, behaves similarly to the animal dynamins. The association of ADL6 with clathrin-coated vesicles was demonstrated by co-fractionation and immunocytochemical studies. ADL6 also interacted via its C-terminus with gamma-adaptin, an adaptor protein of clathrin-coated vesicles. Our results suggest that ADL6 participates in clathrin-mediated vesicle trafficking originating from the Golgi. In addition, our studies demonstrate that ADL6 intrinsic GTPase activity is regulated by its association with acidic phospholipids and an SH3 (Src homology 3)-containing protein.

Adaptor Protein Complex gamma Subunits↗
PubMedDate not supplied

[Surveillance of congenital malformations in Italy: an investigation in the province of Siracusa].

OBJECTIVE: The study describes briefly the current situation of the surveillance of congenital anomalies in Italy and gives an insight into the province of Siracusa in order to better characterise health status of populations residing in an area at high environmental risk. PARTICIPANTS: The authors, who coordinate the Italian registries of congenital malformations, have collaborated with the Eastern Sicily Registry of congenital malformations (ISMAC) and the registry of diseases of the Siracusa province. DESIGN AND SETTING: Data collected by the ISMAC Registry were used to calculate the prevalence of malformed newborns, resident in the municipalities of the province of Siracusa between 1991-2000. This prevalence was compared to that observed in the rest of the Siracusa province (RSP), in the whole area covered by the ISMAC Registry (ESR) and to the mean prevalence at birth of the North-East, Emilia Romagna, Toscana and Campania Registries (IR). Comparisons were made for all malformations and for groups of malformations (with the exclusion of groups with a 10 year frequence <10 cases in the province of Siracusa). In addition, heterogeneity among the municipalities of the province and temporal trends were statistically tested. MAIN OUTCOME MEASURES: Total, groups and specific congenital malformations. RESULTS: Results were statistically borderline considering all malformations when the Priolo-Augusta-Melilli area was compared to IR and ESR (standardized morbidity ratio SMR(IR)=1.1, SMR(ESR)=1.2) and statistically significant when compared to RSP (prevalences ratio PR(RSP)=1.9). Significant excesses resulted in this area also for hypospadias (SMR(IR)=1.9, SMR(ESR)=2.4, PR(RSP)=2.5) and anomalies of the digestive system (SMR(IR)=2.1, SMR(ESR)=1.9, PR(RSP)=2.6). CONCLUSION: Following these results a case-control study on malformations observed in excess has been activated and a protocol for the surveillance of sensitive diseases in areas at environmental risk is being elaborated.

Catchment Area, Health↗
PubMedDate not supplied

[Cause-specific mortality in an area of Campania with numerous waste disposal sites].

OBJECTIVE: To investigate cause-specific mortality in an area of Campania region, in the surroundings of Naples, characterized by many toxic waste dumping grounds sites and by widespread burning of urban wastes. DESIGN: The study area was characterized by examining the spatial distribution of waste disposal sites and toxic waste dumping grounds, using a geographic information system (GIS). Mortality (1986-2000) was studied in the three municipalities of Giugliano in Campania, Qualiano and Villaricca, encompassing a population of about 150,000 inhabitants. Mortality rates of the population resident in the Campania region were used in order to generate expected figures. OUTCOMES: Causes of death of a priori interest where those previously associated to residence in the neighbourhood of (toxic) waste sites, including lung cancer, bladder cancer, leukemia and liver cancer. RESULTS: Overall 39 waste sites, 27 of which characterized by the likely presence of toxic wastes, were identified in the area of interest. A good agreement was found between two independent surveys of the Regional Environmental Protection Agency and of the environmentalist association Legambiente. Cancer mortality was significantly increased, with special reference to malignant neoplasm of lung, pleura, larynx, bladder, liver and brain. Circulatory diseases were also significantly in excess and diabetes showed some increases. CONCLUSIONS: Mortality statistics provide preliminary evidence of the disease load in the area. Mapping waste dumping grounds provides information for defining high risk areas. Improvements in exposure assessment together with the use of a range of health data (hospital discharge cards, malformation notifications, observations of general practitioners) will contribute to second generation studies aimed at inferring causal relationships.

Cause of Death↗
PubMedDate not supplied

[Studying risks of waste landfill sites on human health: updates and perspectives].

OBJECTIVE: Updating current reviews on epidiomiological studies on health effects of waste landfill sites. MATERIALS: Seven ecological studies, two health monitoring investigations and two environmental investigations performed between 2000 and 2004 are discussed. RESULTS: Excesses of risk for cancer incidence, mortality and congenital malformations or no excesses were reported Increasing of low birth weight and different types of symptoms were consistently found. None or very poor environmental data and individual measurements of exposure were available in the majority of the studies. The use of biomarkers and environmental monitoring data to define individual exposure was suggested by some studies. CONCLUSIONS: The development of new and advanced environmental epidemiology studies on health effects of waste sites exposure is now recommended by the scientific community.

Congenital Abnormalities↗