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Biomedical subjects

Roberto Dominici

Publications and source records attributed to Roberto Dominici.

14 recordsLinked to original sources
PubMed2007

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Female↗
PubMed2006

A novel polymorphism in SEL1L confers susceptibility to Alzheimer's disease.

Alzheimer's disease (AD) is considered to be a conformational disease arising from the accumulation of misfolded and unfolded proteins in the endoplasmic reticulum (ER). SEL1L is a component of the ER stress degradation system, which serves to remove unfolded proteins by retrograde degradation using the ubiquitin-proteosome system. In order to identify genetic variations possibly involved in the disease, we analysed the entire SEL1L gene sequence in Italian sporadic AD patients. Here we report on the identification of a new polymorphism within the SEL1L intron 3 (IVS3-88 A>G), which contains potential binding sites for transcription factors involved in ER-induced stress. Our statistical analysis shows a possible role of the novel polymorphism as independent susceptibility factor of Alzheimer's dementia.

Aged↗
PubMed2006

[Biochemical markers for predicting chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use].

Chemotherapy is a well established therapeutic approach for several malignancies, but its clinical efficacy is often limited by related cardiotoxicity leading to cardiomyopathy evolving towards heart failure that may worsen the patient outcome. To detect cardiac damage, the most frequently adopted diagnostic approach is the estimation of left ventricular ejection fraction by echocardiography, showing, however, low sensitivity in early prediction of cardiomyopathy, when appropriate treatments could still improve the patient's outcome. Cardiospecific biomarkers, like cardiac troponins, show high diagnostic efficacy in the early, subclinical phase of disease, becoming positive approximately 3 months before clinical onset of cardiomyopathy. Furthermore, the increase in their concentrations is well correlated with the disease severity and may predict the occurrence of major cardiac events during follow-up. On the other hand, negative troponin concentrations may identify patients with a very low risk of cardiomyopathy (negative predictive value = 99%). For cardiac natriuretic peptides, definitive evidence about a diagnostic or prognostic role in predicting chemotherapy-induced cardiomyopathy is lacking and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined.

Biomarkers↗
PubMed2005

DNA sequence variations in the prolyl isomerase Pin1 gene and Alzheimer's disease.

Senile plaques and neurofibrillary tangles (NFT) are the prominent lesions in the brain of Alzheimer's disease (AD) patients. NFT are mainly composed of an abnormally phosphorylated form of tau protein, which has lost its function to bind microtubules and promote their assembly. Tau hyperphosphorylation critically decreases tau function and precedes neurodegeneration. The majority of tau phosphorylation sites are Ser/Thr-Pro motifs, which are known to exist in two distinct cis and trans conformations. The prolyl isomerase Pin1 catalyses the conversion of those conformations. Pin1 binds to tau specifically at the Thr231-Pro site and restores tau function, either by inducing conformational changes or facilitating dephosphorylation. It has been shown that Pin1 expression levels inversely correlate with the predicted vulnerability of different brain areas to neurodegeneration and soluble Pin1 is depleted in neurons from AD brains; furthermore, Pin1 knock-out mice develop signs and symptoms of tau-related pathologies late in life. It seems that Pin1 plays an important role in maintaining tau function, thereby preserving neuronal homeostasis and preventing age-dependent neurodegeneration. DNA sequence variations in Pin1 gene may affect its expression level or function and influence the individual risk for developing AD. We screened by denaturing high performance liquid chromatography the genomic DNA of 120 AD subjects and 134 age-matched controls and we found very few and rare sequence variations in the promoter region and in exons 2 and 3. We conclude that Pin1 is a very well conserved gene, whose rare nucleotide variations have no effect on the individual genetic risk for AD.

Aged↗
PubMed2005

Influence of the Glu298Asp polymorphism of NOS3 on age at onset and homocysteine levels in AD patients.

The distribution of the Glu298Asp polymorphism in NOS3 gene was determined in 405 Italian patients with "probable" Alzheimer's disease (AD) compared with 253 age-matched controls. Total plasma homocysteine (tHcy) levels were evaluated in 97 patients and 23 controls, and were correlated with the Glu298Asp genotype. A significantly increased frequency of the Glu/Glu genotype in late onset AD (LOAD) patients was found. tHcy levels were significantly increased in patients compared with controls and, notably, higher in LOAD than in early onset AD (EOAD). Stratifying by the Glu298Asp genotype, a trend toward an increase of tHcy was present in Glu/Glu homozygous. This wild type genotype seems to be associated with LOAD. tHcy levels are significantly increased in AD compared with controls and, moreover, higher in LOAD than in EOAD, possibly in correlation with the microvascular disease occurring with aging. Besides, a contribution of the Glu/Glu genotype in increasing tHcy levels has been observed.

Age Distribution↗
PubMed2005

Apolipoprotein E haplotyping by denaturing high-performance liquid chromatography.

The apolipoprotein E ( APOE ) gene in humans contains two single-base polymorphisms in exon 4, which result in three common alleles, conventionally named epsilon2 , epsilon3 and epsilon4 . Numerous studies have shown an important association between the epsilon4 variant and an increased risk of Alzheimer's disease; other data suggest a possible linkage of APOE genetic heterogeneity with lipid profile and an increased risk of atherothrombotic stroke and coronary heart disease. APOE genotyping is therefore an increasingly common assay in laboratory medicine. The most widely used technique for APOE genotyping is based upon restriction isotyping, i.e., amplification of the fragment of exon 4 containing the most common sequence variations, followed by enzymatic digestion of the amplicon and fragments analysis by gel electrophoresis. We developed a novel, reliable and fast method that exploits the sensitivity and specificity of denaturing high-performance liquid chromatography in detecting single-nucleotide polymorphisms. We show that, in most cases, with a single chromatographic separation it is possible to correctly identify the six different APOE allelic patterns, without any manipulation after the polymerase chain reaction amplification. When compared to restriction isotyping, our method is much faster, less labor intensive and similarly inexpensive.

Alleles↗
PubMed2004

Measurement of C-reactive protein: two high sensitivity methods compared.

C-reactive protein (CRP) is an acute phase marker and a predictor of the risk of developing atherosclerotic complications. However, as a predictor of this risk, high sensitivity measurements are needed, and high sensitive CRP (hsCRP) assays have been developed. In this study, we experimentally compared two hsCRP assays, based on nephelometry and turbidimetry, both implemented on automated analyzers. Linearity, imprecision, turbidity interference, and results in the assay of 96 samples have been compared. Method comparison of the same two analytical systems in the assay of CRP was also performed on the basis of results in an interlaboratory external quality assessment scheme (EQAS). The two systems were found to perform substantially equally, both in hsCRP and in CRP measurement, but in the hsCRP assay the precision of nephelometry (CV% in the interval 3.0-5.8) was lower than that of turbidimetry (CV% in the interval 1.8-2.3). The classification of results by the two methods into three predefined relative risk classes gave 18% rate of discordance, in any case by one class only. The two methods proved reliable and comparable in the measurement of hsCRP, but precision should be improved.

Arteriosclerosis↗
PubMed2004

Plasma or serum samples: measurements of cardiac troponin T and of other analytes compared.

Conflicting data in the literature concern possible differences in the immunochemical measurement of cardiac troponins, either in plasma or in serum. In order to address this specific point, 96 serum and heparin-plasma pairs were obtained for cardiac marker measurement [cardiac troponin T (cTnT); myoglobin (Myo) and creatine kinase-MB isoenzyme (CK-MB)]; 29 additional "common" analytes were measured in 77 such samples. The cardiac markers were measured by electrochemiluminescence (Elecsys 2010, Roche); the other analytes by established automated methods (Modular, Roche). Mean plasma/serum ratios for cTnT (0.95), creatine kinase-MB (1.01) and myoglobin (0.99) were comparable with those of the 29 common analytes (interval of means 0.83-1.05). The distribution of the plasma-serum differences also showed similarities between cardiac markers and other analytes. A few outlier plasma-serum differences (3-5%) were measured for both categories of analytes. Addition of heparin to serum (51 samples) caused decreased cTnT (mean ratio 0.92). In 3 of 51 such samples the cTnT decrease was more marked, but in a second sample from the same subjects (1 week later) such a prominent, heparin-induced loss of cTnT no longer appeared. In conclusion, plasma-serum differences in immuno-reactive cTnT compare with those observed for other analytes. In occasional heparin-plasma samples immunochemical measurement of cTnT may give exceptionally low values. However, in our sample group of 96 patients (cTnT lower or higher than the cut-off in, respectively, 24 and 72 patients), no misclassification occurred if plasma instead of serum cTnT values were considered.

Biomarkers↗
PubMed2004

Clinico-pathological significance of cell-type-specific loss of heterozygosity on chromosome 7q21: analysis of 318 microdissected thyroid lesions.

A careful pathological examination often reveals the presence of different lesions at various stages of tumor progression and invasion, even in those thyroid glands presenting with solitary nodules. Each thyroid lesion is composed of many different cell types, reflecting the marked heterogeneity of normal thyroid tissue. Among the different chromosome regions altered in thyroid tumors, 7q21 appears to be specifically involved in malignant tumors, especially of the follicular type. This study was conducted to analyze the loss of heterozygosity (LOH) pattern at 7q21 in pure populations of cells from each single lesion harbored in surgically removed thyroid glands, and to evaluate its clinical significance. One hundred and forty-two thyroid glands were examined, all showing, as a common trait, a goitrous appearance associated with one single lesion in 114 cases and with more than one in the remaining 28 cases. A total number of 318 lesions was analyzed, consisting of 142 goiters (TG), 48 hyperplasias (TH), 80 adenomas (TA) and 48 carcinomas (TC). Five different types of cells were isolated by laser capture microdissection from each lesion. DNA was analyzed by PCR and polyacrylamide gel electrophoresis in search of LOH affecting five microsatellite markers, D7S660, D7S630, D7S492, D7S657, and D7S689. We detected LOH at 7q21 not only in thyroid malignant tumors but also in benign lesions. Allelic loss occurred exclusively in dark nucleus and eosinophilic cytoplasm cells, commonly observed in the follicular type of lesions. In these types of lesions allelic loss frequency increases along with neoplastic transformation (9% in TG, 41% in TH, 68% in TA and 100% in TC), and is directly correlated with thyroid gland volume as well as with the presence of multiple lesions. The highest LOH rate was observed for D7S492, indicating that the recurrent region of deletion was localized at the corresponding genetic locus at 7q21.2, in the same position where the common fragile site FRA7E was previously mapped. LOH at this locus represents an early event in the development of follicular TC and is associated with intense growth of thyroid glands.

Adenocarcinoma, Follicular↗
PubMed2002

Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1 alpha.

A strong correlation between the TT(-889) genotype over CC(-889) of the interleukin-1 alpha (IL-1 alpha) transcription regulatory region and age of Alzheimer's disease onset has recently been reported. To determine the functional effects of the genetic variants on plasma protein levels, we cloned the promoter region and determined its activity. The TT genotype significantly increased the transcriptional activity of the IL-1 alpha gene with respect to the CC genotype. A slight increase of the IL-1 alpha mRNA and protein levels was also observed in the plasma.

Alleles↗
PubMed2002

The Interleukin 1-beta exonic (+3953) polymorphism does not alter in vitro protein secretion.

Several studies have described polymorphisms in the genes encoding interleukin-1alpha (IL-1alpha) and IL-1beta cytokines and their implication in the onset of Alzheimer disease or in linkage disequilibrium with an as yet to be identified second locus on chromosome 2. However, these results have been associated with the sporadic forms of Alzheimer disease. Here we present data on the effects of the interleukin 1-beta exonic polymorphism (+3953) using a series of cohort healthy control samples and in vitro protein secretion assays.

Cohort Studies↗
PubMed2002

Intermethod variation in serum carcinoembryonic antigen (CEA) measurement. fresh serum pools and control materials compared.

This study was undertaken to evaluate the feasibility of using commercial control materials in a regional external quality assessment scheme (EQAS) for serum carcinoembryonic antigen (CEA) measurement. We have assessed the commutability of 12 commercial control materials using five automated immunochemical systems. We compared the intermethod behavior of the materials with that of 12-14 patient serum pools. In a total of 48 comparisons (12 materials x 4 pairs of analytical systems), seven instances of non-commutability were apparent, as shown by normalized residuals falling outside the +/-3 interval. The use of non-commutable materials generates two negative effects. In EQAS, the interlaboratory variation recorded is not representative of the variation expected in the assay of patient sera; in interlaboratory harmonization programs, recalibration with non-commutable materials increases, instead of decreasing, the interlaboratory variation. Both these effects were shown to occur in CEA measurement with the tested materials and systems. The materials planned to be used in our EQAS turned out to be commutable: this gave us the guarantee of measuring realistic interlaboratory variation values, although the check for commutability should be extended to all the analytical systems used by the participants in the scheme.

Calibration↗
PubMed2002

Fecal elastase-1 as a test for pancreatic function: a review.

Pancreatic elastase-1 is a specific human protease synthetized by the acinar cells. Immunoreactive elastase-1 cannot be detected in either porcine or bovine pancreatic enzyme preparations. It is very stable and, in contrast to fecal chymotrypsin, elastase is unaffected by exogenous pancreatic enzyme treatment, and correlates well with exocrine pancreatic function tests. The measurement of this proteolytic enzyme in stool by means of an enzyme-linked immunosorbent assay (ELISA) is a sensitive, specific, and relatively inexpensive non-invasive test. It is an accurate function test for patients with chronic pancreatitis confirmed by endoscopic retrograde cholangiopancreatography and computerized axial tomography. It shows higher sensitivity and specificity for exocrine pancreatic insufficiency than fecal chymotrypsin determination and is comparable to oral pancreatic function tests such as the pancreolauryl test.

Animals↗