Association of folate transporter SLC19A1 polymorphisms with the outcome of multiple myeloma after chemotherapy and tandem autologous transplantation.
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Publications and source records attributed to A M Rossi.
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In this preliminary work the EPR spectra of a small dental enamel block and a synthetic B-type hydroxyapatite in powder form, both irradiated with gamma rays, were analyzed in K-band. The spectra of the dental enamel block allow the analysis of independent components with different angular orientations, while the study of the dosimetric properties of the synthetic hydroxyapatites showed good performance of this spectrometer. K-band spectra show better resolution when compared to X-band, while using significantly less sample material.
PURPOSE: To evaluate genetic damage and oxidative stress following a single therapeutic dose of 131I in Graves' disease patients monitored up to 180 days after treatment. MATERIALS AND METHODS: Genetic damage induction was estimated as the increase in micronuclei in peripheral lymphocytes of patients. As indicators of radiogenic oxidative stress, vitamin E and lipoperoxide levels were assessed in the plasma of patients, as well as the release of plasmic clastogenic factors measured by the induction of micronuclei in vitro in peripheral lymphocytes of a healthy donor. RESULTS: Vitamin E depletion lasted at least 3 days and the basal level was restored within 7 days. No statistically significant variations were observed in lipoperoxide plasma levels. A sharp increase of micronuclei in the peripheral lymphocytes of patients was correlated (p < 0.001) with the release of clastogenic factor in the plasma. The highest micronucleus value was negatively correlated (p < 0.03) with the lowest vitamin E level observed in each patient. CONCLUSIONS: Micronuclei induction was the direct consequence not only of the energy deposition of 131I on the genetic material, but also of oxidative stress, likely via the release of clastogenic factor.
Human sulfotransferases catalyze sulfate conjugation and 2 polymorphic genes, SULT1A1 and SULT1A2 in this family of transferases have been identified, encoding for 2 isoenzymes with very similar properties and substrate specificities. In order to test the hypothesis that variability in sulfation is due to genetic polymorphism in SULT1A1, the sulfation rate of 4-nitrophenol, a diagnostic substrate, was measured in 50 human liver samples and the genotype at the SULT1A1 locus was analyzed. The rate of 4-nitrophenol sulfation varied from 473 - 1,405 pmol/min/mg between the 5th and 95th percentiles, with a median and a mean +/- SD of 757 and 807 +/- 292 pmol/min/mg, respectively. The activities detected among the SULT1A1*2/*2 homozygotes (5 cases) were significantly lower than those of the other 2 genotypes, SULTA1*11/*1 and SULT1A1*1/*2 (5 and 40 cases, respectively), whereas there was no significant difference found between the SULT1A1*1/*1 and SULT1A1*1/*2 genotypes. To evaluate the possible influence of SULT1A2 polymorphism, genotype assays were also performed for this locus. No SULT1A2*2/*2 carrier, 26 SULT1A2*1/*1 and 24 SULT1A2*1/*2 were detected in the population sample under study. However, no correlation between the rate of 4-nitrophenol sulfation and the SULT1A2 genotype was detected. These results confirm that the variation in the rate of 4-nitrophenol sulfation in human liver is mainly due to SULT1A. Since SULT1A1*1/*2 polymorphism accounts for no more than 10% of the phenotypic variation seen in this cohort, other factors must also contribute to the variability in the rate of 4-nitrophenol sulfation in human liver. However, on the basis of the data obtained, variations in age, gender and liver function as possible causative factors can be excluded. The IC50 of quercetin, a potent inhibitor of 4-nitrophenol sulfation, was measured in the liver samples and ranged from 4.6 to 17.3 nM between the 5th and 95th percentiles. The median and the mean +/- SD were 7.7 nM and 8.3 +/- 2.5 nM, respectively. There was a weak but significant correlation between the IC50 value and age of the liver donors (r = 0.283, p = 0.046). The observed variation did not correlate with the genotypes at the SULT1A1 and SULT1A2 loci.
Porous hydroxyapatite (HA) has already been widely used as a bone substitute due to its similarity with the mineral part of the bone. In this work, cylindrical tablets with micro and macro porosity were produced from stoichiometric and deficient hydroxyapatites by using naphthalene as porosifier agent. The influence of the processing parameters such as Ca/P ratio of start material, calcination temperature, and naphthalene content on the characteristics of porous calcium phosphate tablets was evaluated. Three mineral phases-HA, alpha-TCP (alpha tri-calcium phosphate), and beta-TCP (beta tricalcium phos-phate)-with variable contents were identified by x-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FT-IR). Image analysis and density measurements were used to characterize sample porosity. As expected, the total porosity of the calcinated material is not dependent on the stoichiometry of the precursor hydroxyapatite. For calcium-deficient hydroxyapatite, the increase in naphthalene content contributes to stabilize alpha-TCP phase, altering the relative phases content.
Synthetic A-type carbonated apatite prepared in controlled conditions was irradiated at room temperature with 60Co gamma rays. The ESR spectrum was associated to axial CO2- and orthorhombic CO3- species. Radicals used as dose markers in biological apatites are long-lived paramagnetic species. The stability of the post-irradiation signal of A-type apatite was investigated for almost 2 years. Measurements showed variations in the spectra attributed to unstable CO3- species, which can be eliminated by thermal treatments at 100 degrees C for 24 h. Results indicated the potential use of an A-type carbonated apatite as a dosemeter.
Polycrystalline CaSO4 powder, doped with different elements but mainly rare earths, is one of the most interesting thermoluminescent (TL) materials. Although many electron spin resonance (ESR) analyses have been reported for these materials few studies have been published about the potential of CaSO4 for ESR dosimetry; almost all studies used CaSO4:Dy with a very low Dy concentration as the material for TL measurements. Pure CaSO4 from Merck was used to prepare CaSO4:Dy and CaSO4:P:Dy with different Dy concentrations. Samples were annealed at 600 degrees C for 1 h before irradiation in a Gammacell 220 irradiator with a 60Co gamma source at a dose rate of 100 Gy x min(-1). The ESR spectra of the pure CaSO4 and CaSO4 doped with P and Dy show the lines usually observed with these types of material, with the factor g around 2.036 and an intense line at g = 2.0011 found only in the pure material. This line, probably an axial SO4-, grows linearly with absorbed dose until 1.0 kGy and shows good stability with time. The line should be stabilized by matrix impurities because it can be removed by a simple treatment with hot sulphuric acid.
OBJECTIVE: The aim of the present study was to estimate the concordance rate between erythrocyte thiopurine methyltransferase (TPMT) activity and genotype at the TPMT locus in an Italian population sample. METHODS: The TPMT phenotype and genotype were determined in an unrelated population of 103 Italian healthy blood donors. Erythrocyte TPMT activity was measured with a radiochemical assay using 12.5 microM S-adenosyl-L-(methyl-14C)-methionine and 4 mM 6-mercaptopurine. The genotyping assay was based on restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) methods. RESULTS: All subjects had detectable TPMT activity. The activity of TPMT varied 2.8-fold between the 5th and 95th percentile. This variation was neither age (P = 0.63) nor gender (P = 0.44) regulated and the frequency distribution of TPMT activity is compatible with a polymorphic distribution. The presence of the four most common defective alleles, i.e. TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C, was examined through the entire phenotyped population. Ninety-two subjects did not carry any of the tested mutations. Eleven individuals were heterozygous for one of the mutant alleles and had a TPMT activity lower than 30 pmol/min/mg. Eight subjects were TPMT*1/TPMT*3A, two TPMT*1/TPMT*3C and one was TPMT*1/TPMT*2. The TPMT*3B allele was not detected in the samples analysed. CONCLUSION: There was a concordance of 97% between genotype and phenotype. All the heterozygotes had an intermediate phenotype. However, the wide variation range in TPMT activity detected in the wild-type homozygotes indicates that other genetic or epigenetic factors influence the TPMT phenotype.
Synthetic A-type carbonated apatite samples were irradiated at room temperature with 60Co gamma rays. Their ESR spectra consist of the lines of CO2- and CO3- radicals of orthorhombic and axial symmetry. The measurements carried out immediately after sample irradiation showed that CO2- species are produced by decomposition of CO3- radicals. Intensity of the CO2- lines in the synthetic and enamel samples increases during the first 400 and 200 h after irradiation, respectively. The dependence of the EPR signal on the dose varies with carbonate content of the sample. The dose response curve for tooth enamel is steeper for the synthetic material.
Electron spin resonance (ESR) spectroscopy is used to assess absorbed doses of six teeth belonging to victims of the highly irradiated group of Goiânia accident. The influence of the broad background signal at g = 2.0040 as well as of the unstable fraction of CO2- radicals was taken into account in dose estimates. Three victims teeth showed absorbed doses comparable to those estimated by chromosomal analysis. For the other three teeth, the doses were higher by a factor of 1.3, 1.8 and 2.2.
In 1996, 10 years after Chernobyl accident, a cytogenetic analysis was carried out to assess whether chromosome aberrant cells (CA) were still detectable in the lymphocytes and clastogenic factors (CFs) were present in the plasma of children coming from Gomel (Belarus), one of the most heavily contaminated regions. Furthermore, the possible contribution of plasmatic CFs to the amount of CA was investigated. The presence of CA was examined in the lymphocytes from 29 thyroid tumour-affected children and 41 healthy children (local controls). Thirty healthy children living in Pisa (Italy) were enrolled in the study as additional controls from an uncontaminated area. No significant difference was observed between the two control groups, whereas a significantly increased frequency of CA was found in the tumour-affected children, as compared with Gomel and Pisa controls (chi 2-test, p < 0.001). However, when soil contamination level was taken into account, the chromosome type CA frequency observed in tumour-affected children coming from the more contaminated areas (> 4 Ci/km2) resulted significantly higher than that in other children, either affected or not (p = 0.003). The presence of CFs was analyzed on the plasma ultrafiltrate from 41 children. 7/10 (70%) plasma samples from tumour-affected children and 17/23 (74%) Gomel controls resulted to possess clastogenic activity irrespective of soil contamination levels. No activity was detected in the plasma of eight Pisa controls (0%). The difference between both Gomel groups and Pisa controls was highly significant (p = 0.002). A borderline, but not statistically significant correlation (p = 0.08) was observed between basal CA frequency and CF potency, which became significant (p = 0.03) when only chromosome type of aberrations was considered. We conclude that, although the presence of CFs in the plasma of these children might be partly responsible of the cytogenetic effects observed, the main source of damage has considered to be do to the previous and/or continuous exposure to environmental radiocontaminants. Tumour-affected children may represent a subset of the population either more sensitive to clastogenic damage or exposed to higher levels of contaminants.
Most studies on the effects of elevated CO2 have focused on the effects on plant growth and ecosystem processes. Fewer studies have examined the effects of elevated CO2 on herbivory, and of these, most have examined feeding rates in laboratory conditions. Our study takes advantage of an open-top CO2 fertilization study in a Florida scrub-oak community to examine the effects of elevated CO2 on herbivore densities, herbivore feeding rates, and levels of attack of herbivores by natural enemies. Higher atmospheric CO2 concentration reduced plant foliar nitrogen concentrations, decreased abundance of leaf-mining insect herbivores, increased per capita leaf consumption by leafminers, and increased leafminer mortality. As suggested by other authors, reduced foliar quality contributed to the increase in herbivore mortality, but only partly. The major factor increasing mortality was higher attack rate by parasitoids. Thus increasing CO2 concentrations may reduce the survivorship of insect herbivores directly, by reducing plant quality, but also indirectly, by changing herbivore feeding and eliciting greater top-down pressure from natural enemies.
The role of genetic polymorphism in modulating urinary excretion of two benzene metabolites, i.e. trans,trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (PMA), has been investigated in 59 non-smoking city bus drivers, professionally exposed to benzene via vehicle exhausts. Exposure to benzene was determined by personal passive samplers (mean +/- SD = 82.2 +/- 25.6 micrograms/m3), while internal dose and metabolic rate were evaluated by measuring urinary excretion of unmodified benzene (mean +/- SD = 361 +/- 246 ng/l), t,t-MA (mean +/- SD = 602 +/- 625 micrograms/g creatinine), and PMA (mean +/- SD = 5.88 +/- 4.76 micrograms/g creatinine). Genetic polymorphism at six loci encoding cytochrome-P450-dependent monooxygenases (CYP2E1 and CYP2D6), glutathione-S-transferases (GSTT1, GSTP1 and GSTM1) and NAD(P)H:quinone oxidoreductase (NQOR) was determined by polymerase chain reaction-based methods. No evidence emerged for a possible role of CYP2E1, GSTM1 and GSTP1 polymorphisms in determining the wide differences observed in the rate of benzene biotransformation. Conversely, a significantly higher t,t-MA urinary excretion was found to be correlated to, GSTT1 null genotype, and a significantly lower PMA excretion was detected in the subjects lacking NQOR activity and in the CYP2D6 extensive-metabolizers. Many biological (i.e. age and body burden) or lifestyle factors (i.e. rural or urban residence, use of paints and solvents, medication, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlations found. These findings suggest that CYP2D6, GSTT1 and NQOR polymorphisms contribute in explaining the metabolic variability observed in our sample. Therefore, these polymorphisms should be regarded as potential risk factors for benzene-induced adverse health effects.
The outcome of 103 pregnancies in 64 women with constant hyperprolactinemia was evaluated. Seventy-eight pregnancies had been induced with bromocriptine and 25 occurred without any treatment. In all, 66% of the pregnancies ended in delivery, 17% in miscarriage, 10% in tubal pregnancy and 7% in induced abortion. The pregnancy of women with untreated hyperprolactinemia was more frequently ectopic when compared to those in women treated by bromocriptine. Obstetric complications as well as signs of tumoral enlargement during pregnancy were rare in hyperprolactinemic women treated or untreated with bromocriptine. Untreated hyperprolactinemia as a risk factor in tubal pregnancy is proposed.
In this work we combine electron paramagnetic resonance (EPR), high-resolution electron nucleus double resonance (ENDOR) and general triple resonance (GTR) spectroscopies, to study the local environment of the CO2- groups created by ionizing radiation in fossil tooth enamel. We demonstrate that the CO2- groups occupy slightly modified phosphate sites in the hydroxyapatite lattice. In quaternary shark enamel we found these groups to be interacting with water molecules in the apatite channels. The absence of water molecules as first neighbors in mammalian samples indicate, however, that these molecules are not significantly responsible for the stabilization of CO2- dating centers in enamel.
BACKGROUND: Aging and diabetes mellitus have been recognized as strong predictors of heart failure in patients with acute myocardial infarction. The aim of this study was to assess, by echocardiography, the influence of aging and non-insulin-dependent diabetes mellitus on the changes of left ventricular parietal kinesis in patients with acute myocardial infarction over the 6 months after hospitalization. METHODS: The study population consisted of 82 patients (42 male, 40 female) aged 70 years, consecutively admitted to coronary care unit with acute myocardial infarction from January 1991 to May 1993. They were divided into two groups: group 1 comprised 36 patients with non-insulin-dependent diabetes mellitus, aged 78.8 +/- 6.02 years, 17 men and 19 women; group 2 comprised 46 patients without diabetes aged 78.7 +/- 6.9 years, 25 men and 21 women. Echocardiography was performed at admission to the unit (T0), at discharge (T1), and after 6 months of follow-up (T2). The echocardiographic wall motion score index was calculated by considering the number of akinetic and dyskinetic left ventricular wall segments. Fatal and non-fatal incidents of heart failure were also considered and a multivariate analysis was applied to identify the clinical and instrumental parameters that were independent predictors of wall motion score index changes and heart failure events. RESULTS: At T1 the two groups were comparable in localization of acute myocardial infarction, previous myocardial infarction, creatinine kinase serum peak, ECG score and wall motion score index. A statistically significant reduction in akinesia (P < 0.001) was observed in group 2 at T1 and T2, but was not seen in group 1. At T2 the difference in wall motion score index between the groups became significant (P < 0.05). The occurrence of heart failure was significantly higher in group 1 than in group 2 either during hospitalization (P < 0.03) or during follow-up (P < 0.004). The multivariate analysis identified non-insulin-dependent diabetes mellitus as an independent predictor of lacking recovery in LV kinesis (P < 0.01) and of heart failure development (P < 0.001). CONCLUSION: In elderly patients with non-insulin-dependent diabetes mellitus lack of recovery in wall motion score index after acute myocardial infarction seems to be an important factor, with a higher heart failure prevalence adversely affecting the in-hospital and long-term outcome. Non-insulin-dependent diabetes mellitus appears to be an important factor related to this unfavorable outcome.
Molecular analysis of hypoxanthine-guanine phosphoribosyltransferase (hprt) cDNA from 6-thioguanine-resistant T-lymphocytes cloned from smoking and non-smoking adult donors showed that 35% of these mutants were defective in splicing of hprt mRNA. Among a set of 42 hprt splice mutants, we observed i) complete loss of one or more exons, ii) partial loss of one exon, or iii) inclusion of part of an intron sequence between adjacent exons. Loss of exon 4 was significantly more frequent than of the other exons, suggesting that the sequences that regulate splicing of this exon are either larger than those of the other exons or especially prone to mutation. In order to identify the molecular nature of DNA alterations causing aberrant splicing of hprt mRNA, 17 splice mutants were analyzed in more detail by sequencing the genomic regions flanking the mis-spliced exon. Base pair substitutions or small deletions causing defective splicing were either detected in exon sequences or in splice site consensus sequences of introns. Furthermore, genomic deletions encompassing entire exons were found. In some mutants, the alteration responsible for incorrect splicing could not be identified, suggesting that the target sequence for splice mutations is larger than merely the splice junctions. Molecular characterization of hprt splice mutations will lead to the identification of specific sequences regulating splicing of hprt mRNA and will reveal whether the mutational spectrum in splice mutants is similar to that found in the hprt coding region.
Transforming growth factor beta (TGF beta) is an extremely potent chemoattractant for macrophages, mononuclear leukocytes, and fibroblasts. It also acts as a potent stimulant for collagen and fibronectin synthesis and inhibits epithelial cell growth. TGF beta plays an important role in healing many types of wounds, but its role in peritoneal adhesion formation is not known. These studies were performed to determine if TGF beta could affect postoperative wound healing in a rat model. In the first experiment, 20 rats were divided into two groups and received either 2 micrograms TGF beta or control diluent IP daily for 5 days after surgical injury to the uterine horns. The severity of the adhesions were graded 2 weeks postoperatively using a score of 0-3. The TGF beta group showed a higher adhesion score at 2 weeks compared to control, 2.9 +/- 0.34 and 1.6 +/- 0.61, respectively (P less than 0.001). On H&E stained sections of the adhesions, there was an increase in the number of both inflammatory cells and fibroblasts in the TGF beta-treated animals. A comparison trial of bone-derived TGF beta (a gift from Collagen Corporation, Palo Alto, CA) versus recombinant TGF beta (a gift from Oncogen, Seattle, WA) versus control using the same protocol as above showed that both sources of TGF beta were more effective in promoting postoperative adhesions when compared to controls, and there was no difference between TGF beta groups, 3.0 +/- 0 for both TGF beta groups, and 2.2 +/- 0.91 for control (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)