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Biomedical subjects

M Betti

Publications and source records attributed to M Betti.

At least 19 recordsLinked to original sources

Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma in a general population study.

Differences in response to carcinogenic agents are due to the allelic variants of the genes that control it. Key genes are those involved in the repair of the DNA damage caused by such agents. This paper describes the results of a case-control epidemiological study designed to determine the genotypes of four of these genes in persons exposed to a single genotoxic factor, i.e. asbestos, who had or had not developed malignant mesothelioma (MM). Our working hypothesis was that an imperfect DNA repair, as revealed by subtle polymorphic variants, could reduce protection against the chronic DNA insult provoked by asbestos and eventually result in mutagenesis and cancer. Seven variants (i.e. XRCC1-R399Q-NCBI SNP, XRCC1-R194W, XRCC3-T241M, XRCC3-IVS6-14, XPD-K751Q, XPD-D312N, OGG1-S326C) were investigated in 81 patients and 110 age and sex-matched controls, all residents at Casale Monferrato, a Piedmontese town highly exposed to asbestos pollution. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When considered as a categorical variable, XRCC1-399Q showed an increased OR both in heterozygotes (OR=2.08; 95% CI=1.00-4.33) and homozygotes (2.38; 95% CI=0.82-6.94), although individual ORs were not significant. When it was considered as a continuous variable OR was significant (OR=1.68; 95% CI: 1.02-2.75). When genotypes were divided into "non-risk" and "risk" genotypes, i.e. those thought to be associated with increased risk in the light of the functional significance of the variants, XRCC1-399Q (Q homozygotes+Q/R heterozygotes versus R homozygotes) had an OR=2.147 (95% CI: 1.08-4.28), whereas that of XRCC3-241T (T homozygotes+M/T heterozygotes versus M homozygotes) was 4.09 (95% CI: 1.26-13.21) and that of OGG1-326C was increased, though not significantly. None of the haplotypes showed a significantly different frequency between patients and controls. This is the first report of an association between polymorphisms in DNA repair genes and asbestos-associated MM. Our data indicate that genetic factors are involved in MM development.

Aged↗

Characterization of the NIST seaweed Standard Reference Material.

The National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) for seaweed was developed through an interlaboratory comparison with 24 participants from 16 countries. After evaluating different techniques to calculate certified values for the radionuclides, the median method was found to be the most representative technique. The certified values were provided for 13 radionuclides and information values were given for 15 more radionuclides. Results for the natural decay series showed disequilibrium in both the uranium and thorium series.

International Cooperation↗

Effects of Fe(II) and hydrogen peroxide interaction upon dissolving UO2 under geologic repository conditions.

Iron redox cycling is supposed to be one of the major mechanisms that control the geochemical boundary conditions in the near field of a geologic repository for UO2 spent nuclear fuel. This work investigates the impact of reactions between hydrogen peroxide (H2O2) and iron (Fe2+/Fe3+) on UO2 dissolution. The reaction partners were contacted with UO2 in oxygen-free batch reactor tests. The interaction in absence of UO2 gives a stoichiometric redox reaction of Fe2+ and H2O2 when the reactants are present in equal concentration. Predomination of H202 results in its delayed catalytic decomposition. With UO2 present, its dissolution is controlled by either a slow mechanism (as typical for anoxic environments) or uranium peroxide precipitation, depending strongly on the reactant ratio. Uranium peroxide (UO4 x nH2O, m-studtite), detected on UO2 surfaces after exposure to H2O2, was not found on the surfaces exposed to solutions with stoichometric Fe(II)/ H2O2 ratios. This suggests that H2O2 was deactivated in redox reactions before a formation of UO4 took place. ESR measurements employing the spin trapping technique revealed only the DMPO-OH adduct within the first minutes after the reaction start (high initial concentrations of the OH radical); however, in the case of Fe(II) and H2O2 reacting at 10(-4) mol/L with UO2, dissolved oxygen and Fe2+ concentrations indicate the participation of further Fe intermediates and, therefore, Fenton redox activities.

Geological Phenomena↗

The influence of extraction and precipitation pH on the dry matter yield of broiler dark meat.

In recent years, demand for white meat products has resulted in excess supplies and depressed prices of leg meat in the United States. One approach to increasing the utilization of dark meat is to extract the pigments and fat to make the resulting product more acceptable for the production of further-processed meat products. To date, such technologies have been inefficient (low yields) or have resulted in products of limited use. Three replicate trials were conducted to determine the effects of extraction pH and precipitation pH on the wet and dry extract yields of boneless, skinless broiler leg meat. Broiler leg meat was chopped with added water and extracted by adjusting the pH to 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 11.5, and 12.0 while mixing. After determination of extraction yields, each extraction was adjusted to pH 3.8, 4.0, 4.2, 4.4, 4.6, 4.8, 5.0, and 5.2 to determine the effect of precipitate pH on total wet and dry yields. Dry yield increased with extraction pH and precipitation pH. However, the greatest yields, over 70%, were at extraction pH values above 10.5, which have been associated with the production of potentially harmful by-products. Combinations of extraction pH values between 9 and 10.5 and precipitation pH values above 4.4 resulted in dry yields of approximately 65%. These results indicate that pH extraction and precipitation may result in economically viable yields. Further research is needed to determine the optimal conditions of yield, composition, and functionality.

Animals↗

Results of the European Commission Marina II study: part II--effects of discharges of naturally occurring radioactive material.

Enhanced levels of naturally occurring radioactive materials (NORM) are produced through various industrial operations and may lead to discharges to the marine environment. A recent study, called MARINA II, carried out for the European Commission considered discharges of radionuclides from the NORM industries to north European marine waters and their consequences. There are two main sources that were considered in the study. The use of phosphogypsum during the production of phosphoric acid by the fertiliser industry and the pumping of oil and gas from the continental shelf in the North Sea which produces large quantities of water contaminated with enhanced levels of naturally occurring radionuclides. Discharges of alpha emitting radionuclides from these two industries have contributed significantly to the total input of alpha emitters to north European waters over the period 1981-2000 (data were not available prior to 1981). Discharges due to the use of phosphogypsum have declined since the early 1990s and are now very low. Discharges from the oil and gas industries stabilised in the second half of the 1990s and are now the major contributor to alpha discharges to the region. As most European countries do not report discharges of radioactivity with the water produced during extraction, there is considerable uncertainty in the discharges used in the study. The impact of the discharges has been estimated both in terms of the effect on non-human biota and the radiological impact for people. In the 1980s the radiation dose rates to marine biota in the region around a phosphate plant on the north-west coast of England were as high due to the discharges from the phosphate plant as those near to the Sellafield reprocessing plant due to its discharges. In recent years the additional dose to marine biota in this region due to the past NORM discharges is of the same order of magnitude as the natural background. The collective dose rate was estimated to determine the radiological impact on people. The peak collective dose rate from the NORM industries occurred in 1984 and was just over 600 manSv y(-1). The collective dose rate fell with time as discharges from the phosphate industry reduced and was estimated as under 200 manSv y(-1) in 2000.

Chemical Industry↗

Results of the European Commission MARINA II study: part I--general information and effects of discharges by the nuclear industry.

From the collated data relevant to discharges by the nuclear industry, it results that the input of beta activity (excluding Chernobyl fallout and tritium) into the OSPAR region decreased by a factor of 4 from 1986 to 1991, reaching by this date the same level as in the early 1950s. Over the same period the discharges of the alpha activity into the OSPAR region also decreased by a factor 3, the same trend has been seen also for tritium. Since 1986 the effective dose to members of the critical group in the vicinity of Sellafield and Cap de La Hague was consistently below the ICRP and EU limit of 1 mSv per year to members of the general public. The overall radiological impact from nuclear industry on the population of the European Union from the OSPAR area has decreased from 280 manSv y(-1) in 1978 to 14 manSv y(-1) in 2000.

Environmental Monitoring↗

Color variation and characterization of broiler breast meat during processing in Italy.

The variation in broiler breast meat color (CIE values L*a*b*) that normally occurs during processing was evaluated on 6,997 broiler breast fillets (pectoralis major muscles) from 79 flocks using a Minolta Chroma Meter. The samples were randomly collected at 3 to 6 h postmortem from the deboning line at a single major Italian processing plant. In addition, 216 fillets were selected based on lightness (L*) values as being dark (L* < 50), normal (50 < or = L* < or = 56), or pale (L* > 56), and were analyzed for ultimate pH, intact and ground meat cooking loss, and shear value. The overall range in measured lightness (L*) was considerable and varied from 40 (dark) to 66 (pale), indicating that high breast meat color variation during processing could exist. Broiler breast meat during summer was found to be paler (+1.7 L* unit), less red (-1.0 a* unit), and less yellow (-0.7 b* unit) than breast meat samples collected during the winter, confirming that the incidence of pale meat is greater during summer as indicated by nonscientific observations of plant personnel. It was also determined that paler (L* > 56) breast meat is associated with lower ultimate pH and poorer water-holding capacity, whereas darker (L* < 50) breast meat is associated with higher muscle pH and cooking yield.

Animals↗

Sample cleanup by on-line chromatography for the determination of Am in sediments and soils by alpha-spectrometry.

A novel sample cleanup procedure for the Am determination in environmental samples by alpha-spectrometry is described. The method is based on the use of three analytical chromatographic columns. TEVA-Spec. from Eichrom has been packed in an analytical chromatographic column to carry out the lanthanide/actinide separation. A CS5A mixed-bed column from Dionex was used to separate Am from lanthanide impurities and other actinides. A TCC-II column from Dionex was used to connect the TEVA to the CS5A and act as a preconcentrator column for the trivalent ions. The behavior of the columns was studied by coupling the chromatograph to an ICPMS detector. A chromatographic fraction has been used for sample preparation for alpha-spectrometric determination of 241Am. The analytical procedure has been validated with certified reference materials (sediment and soil) and was applied to sediment core samples from the Irish Sea and compared with the classical radiochemical separation of Am.

Americium↗

Deposition and distribution of Chernobyl fallout fission products and actinides in a Russian soil profile.

In this article the distribution of fission products and actinides in a soil profile from Novo Bobovicky in Russia, which was contaminated due to the Chernobyl nuclear power plant accident, is described. The ground deposition of long-lived fission products determined by gamma-spectrometry was (recalculated to 26 April 1986) 1600 kBq (137)Cs/m(2), 900 kBq (134)Cs/m(2) and 60 kBq (125)Sb/m(2). Of these radionuclides (137)Cs shows the dominating activity at the present time. After 6.5 years 90% of the Cs and Sb activity was contained in the upper 4 cm. A (239,240)Pu ground deposition of 77.4+/-8.0 Bq/m(2) was determined by alpha-spectrometry. The (238)Pu/(239,240)Pu activity ratio of 0.30+/-0.03 and (241)Pu/(239,240)Pu activity ratio of 115+/-14 (in 1986) measured in the soil profile, indicates that the analysed Pu originates mainly from the Chernobyl accident. The average (234)U/(238)U activity ratio of 1.06+/-0.29 indicates that the uranium in this soil is dominated by naturally occurring uranium. The alpha- and beta-autoradiography revealed that the activity is mainly present in particulate form. It could further be observed that the spots containing alpha- or beta-activity originated from different particles. A comparison of alpha-autoradiography with the bulk Pu and Am activity showed that 92% of the alpha-activity was present as clearly detectable alpha-spots. The beta-active particles, located by beta-autoradiography were correlated with gamma-spectrometric measurements and contained only (137)Cs. These hot spots ranged from 0.02 to 0.15 Bq.It could be concluded that the vertical transport of (137)Cs and fuel fragments occurs mainly by movement of particles through the soil. It could also be concluded that the fuel fragments found, in this soil were depleted in respect to Cs, Sb and Eu. Comparison of the analysed (238)Pu/(239,240)Pu, (241)Pu/(239,240)Pu and (241)Am/(239,240)Pu ratios with the ratios calculated with ORIGEN-S code gave an estimate of the average burn-up of the fuel particles to be in the range of 11-12 GWd/tU. The results presented in this article are valid for this single soil profile and should not be generalised unless validated in a more rigorous study of a larger number of soil profiles.

Actinoid Series Elements↗

Traceability of inbred and crossbred Cinta Senese pigs by evaluating the oxidative stress.

Previous studies on the oxidative stress in swine indicated a strong link between the values of reactive oxygen metabolites (ROMs), the subsequent antioxidant adaptive response (OXY) and the genetic selection. Such findings, mainly related to a cardiovascular inadequacy in lean, large muscle blocks and fast growing breeds, is associated with specific metabolic diseases such as porcine stress syndrome and mulberry heart disease. In this study, we investigated the oxidative stress parameters to trace the genetics of Cinta Senese (CS) pigs, a historical breed free-range reared in Siena countryside. Sera from CS (n = 24) and Large White x CS (LW x CS) (n = 24) groups around 120 kg body weight fed the same diet were sampled at slaughter. Sera from wild boars (WB) (n = 24) hunted in the same district were also considered. ROMs and OXY were evaluated in the three groups of swine. Significant differences by one-way anova (P < 0.05) between groups were found for both procedures. ROM levels were lower in WB (9.79 +/- 5.76 mm H2O2) and CS (18.02 +/- 7.42 mm H2O2), and highest in LW x CS (42.78 +/- 8.61 mm H2O2). OXY values ranged from 271.37 +/- 50.90 microm neutralized HOCl (WB) to 343.21 +/- 57.45 microm neutralized HOCl (LW x CS). Results indicated that the evaluation of the oxidative stress can effectively trace the CS pigs, thus aiding in preserving the overall specific traits of such a historical animal.

Animals↗

Oxygen isotopic measurements by secondary ion mass spectrometry in uranium oxide microparticles: a nuclear forensic diagnostic.

To exploit oxygen isotopic measurement by SIMS as a diagnostic tool in nuclear forensics, the magnitude and reproducibility of 0-isotope instrumental mass discrimination for O-isotope standards in the SIMS laboratory at the Institute for Transuranium Elements has been evaluated. Tests for matrix-dependent discrimination effects on three different O-isotope standards with substantially different matrix compositions have been performed. The results were checked by an interlaboratory comparison of O-isotope discrimination with those obtained in the SIMS laboratory at the Lawrence Livermore National Laboratory on two standards. The results from the two laboratories are in very good agreement, indicating statistically indistinguishable instrumental mass discrimination factors for 180/160 ratios on the Cameca 6f and 3f, when the analyses are performed under the experimental conditions described. The 2sigma(mean) uncertainties of these factors are in the range of 0.3-0.9%. In accordance with the tested methodology, 0-isotope compositions were measured in three particulate uranium oxide samples of nuclear forensics interest.

Oxygen Isotopes↗

Characterization of HIV-1 Tat proteins mutated in the transactivation domain for prophylactic and therapeutic application.

Previous work from our group showed that genetic immunization of mice with HIV-1 tat genes (tat22 and tat22/37), encoding Tat proteins mutated in the transactivation domain and lacking Tat-transactivating activity, evoke an immune response to wild-type Tat, both humoral and cellular. In the present work we report that the mutated Tat proteins localize within the cells, are released and taken up by the cells in a fashion similar to wild-type Tat. Moreover, the exogenous mutated Tat proteins interfere with the transactivating function of extracellular wild-type Tat. These results support the notion that tat22 and tat22/37 genes may represent good candidates for the development of an anti-HIV-1 vaccine, especially for HIV-1 infected patients.

AIDS Vaccines↗

A plant 3'-phosphoesterase involved in the repair of DNA strand breaks generated by oxidative damage.

Two novel, structurally and functionally distinct phosphatases have been identified through the functional complementation, by maize cDNAs, of an Escherichia coli diphosphonucleoside phosphatase mutant strain. The first, ZmDP1, is a classical Mg(2+)-dependent and Li(+)-sensitive diphosphonucleoside phosphatase that dephosphorylates both 3'-phosphoadenosine 5'-phosphate (3'-PAP) and 2'-PAP without any discrimination between the 3'- and 2'-positions. The other, ZmDP2, is a distinct phosphatase that also catalyzes diphosphonucleoside dephosphorylation, but with a 12-fold lower Li(+) sensitivity, a strong preference for 3'-PAP, and the unique ability to utilize double-stranded DNA molecules with 3'-phosphate- or 3'-phosphoglycolate-blocking groups as substrates. Importantly, ZmDP2, but not ZmDP1, conferred resistance to a DNA repairdeficient E. coli strain against oxidative DNA-damaging agents generating 3'-phosphate- or 3'-phosphoglycolate-blocked single strand breaks. ZmDP2 shares a partial amino acid sequence similarity with a recently identified human polynucleotide kinase 3'-phosphatase that is thought to be involved in DNA repair, but is devoid of 5'-kinase activity. ZmDP2 is the first DNA 3'-phosphoesterase thus far identified in plants capable of converting 3'-blocked termini into priming sites for reparative DNA polymerization.

Amino Acid Sequence↗

Insulin-like effect of zinc in mytilus digestive gland cells: modulation of tyrosine kinase-mediated cell signaling.

The possible effects of zinc in the modulation of the activity of glycolytic enzymes phosphofructokinase and pyruvate kinase through tyrosine kinase-mediated signal transduction in isolated digestive gland cells from mussels (Mytilus galloprovincialis Lam.) were investigated. Addition of micromolar concentrations of zinc resulted in both time- and concentration-dependent stimulation of glycolytic enzyme activities similar to those previously observed with insulin; however, zinc pretreatment prevented the glycolytic effect of insulin in mussel cells. The insulin-like effect of zinc was mediated by increased tyrosine phosphorylation of multiple proteins, as demonstrated by Western blotting with antiphosphotyrosine antibodies. The pattern of zinc-induced phosphorylation resembled that induced by insulin. Moreover, both zinc and insulin induced activation of mitogen activated protein kinases (MAPKs); however, whereas zinc gave a clear effect on the stress-activated p-38 MAPK, insulin activated extracellular-activated MAPK (ERK2) and inhibited p-38. The results demonstrate that zinc can act as a physiological regulator of tyrosine kinase-mediated cell signaling in mussel digestive gland cells, in particular at the level of MAPK activation. Activation of p-38 by zinc may be a key step in prevention of the glycolytic effect of insulin in mussel cells. These data underline the importance of cross talk between different MAPKs in determination of the response to extracellular stimuli in marine invertebrate cells.

Animals↗

Comparison between the use of direct current glow discharge mass spectrometry and inductively coupled plasma quadrupole mass spectrometry for the analysis of trace elements in nuclear samples.

The quantitative determination of trace elements in nuclear samples by GDMS and ICP-MS is presented and compared. Spectral interferences, matrix effects, detection limits, precision and accuracy are discussed. Results for selected samples demonstrated that both techniques are complementary. The use of a multi-standard solution provides the most accurate results in ICP-MS, whereas in GDMS this is achieved by relative sensitivity factors (RSF) matrix matched. Nevertheless, the use of standard RSF allows a fast screening.

Journal Article↗

Ion chromatography inductively coupled plasma mass spectrometry (IC-ICP-MS) and radiometric techniques for the determination of actinides in aqueous leachate solutions from uranium oxide.

The choice of the analytical method for the determination of actinide isotopes in leachate solutions has to be made considering several parameters: detection limit for each isotope, sample preparation procedure in terms of duration and complexity, counting time and interferences. A leachate solution obtained by keeping a pellet of UO2 doped with 238Pu in contact with distilled water was investigated for the content of U and Pu isotopes by radiometric methods (alpha-, gamma-spectrometry and liquid scintillation counting). The results of the radiometric methods were compared with those obtained from the analysis performed by inductively coupled plasma mass spectrometry on-line to a system for chromatographic separation (IC-ICP-MS). The comparison confirmed that IC-ICP-MS is a powerful method for the detection of long-lived radionuclides. The radiometric methods have a detection limit two orders of magnitude lower than IC-ICP-MS in the case of short-lived radioisotopes mostly due to the low background in the detector. On the other hand, the sample preparation and the analysis duration are more time-consuming compared to IC-ICP-MS; moreover, not all isotopes can be determined by using only one radiometric technique.

Journal Article↗

Growth factor-mediated signal transduction and redox balance in isolated digestive gland cells from Mytilus galloprovincialis Lam.

In mammalian cells, a growing body of evidence indicates a relationship between cellular redox balance and tyrosine kinase-mediated cell signalling. The phosphorylative cascade activated by extracellular signals is inhibited by reducing conditions and stimulated by oxidative stress, in particular at the level of mitogen activated protein kinase (MAPK) activation. The mussel Mytilus typically shows variations in antioxidant defence systems and decreases in glutathione content in response to both natural and contaminant environmental stressors. In isolated mussel digestive gland cells, both epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been recently demonstrated to activate tyrosine kinase receptors leading to multiple responses; among these, stimulation of the key glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK). The present study investigates the possible relationship between the tyrosine kinase-mediated metabolic effects of growth factors and cellular redox balance in mussel cells. The results demonstrate that the effects of growth factors on glycolytic enzymes were abolished by cell pretreatment with the antioxidant N-acetyl-cysteine (NAC). On the other hand, in cells where the glutathione content and synthesis were lowered either in vitro (by cell pretreatment with buthionine sulfoximine (BSO)), or in vivo (by mussel exposure to Cu(2+)) the metabolic effects of growth factors were unaffected. Moreover, the results show that, in both control and glutathione-depleted cells, growth factors can also regulate the level of glutathione apparently by modulating, via phosphorylative mechanisms involving MAPK activation, the activity of gamma-glutamylcysteine synthetase (GCS), the rate limiting enzyme in GSH biosynthesis. Overall, this study extends the hypothesis that cell signalling is intimately related to redox balance in marine invertebrate cells.

Acetylcysteine↗