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J Fernández

Publications and source records attributed to J Fernández.

At least 19 recordsLinked to original sources

Kinematically complete study of dissociative ionization of by ion impact.

We present a kinematically complete study of dissociative ionization of D(2) by 13.6 MeV/u S(15+) ions. The experiment allows us to unravel the competing mechanisms, namely, direct single ionization, autoionization of doubly excited states, ionization excitation, and double ionization, and to analyze the corresponding electron angular distribution from fixed-in-space molecules. The conclusions are supported by theoretical calculations in which the correlated motion of all electrons and nuclei and the interferences between them are described from first principles.

Journal Article↗

Determination of genotoxicity of classical swine fever vaccine in vitro by cytogenetic and comet tests.

Chromosome damage in lymphocyte cultures induced by live virus vaccine against classical swine fever (CSF) has been observed in previous studies. In vivo cytogenetic tests were made with several doses of vaccines used in Argentina to control the disease. These studies have shown that genotoxic effects increased with dose. In the present study, two different in vitro assays were performed by recording the frequency of cells with chromosome alterations and by assessing the ability of the vaccine to damage DNA, using the single cell gel microelectrophoretic assay (comet test). Frequencies of cells with chromosomal alterations increased significantly when compared with controls and were dose (microl/ml) dependent: 0 = 1.23, 5 = 2.29, 10 = 5.42 and 20 = 11.71%. In the comet assay the variables measured, tail length (TL) and tail moment (TM), also increased. For control cultures TL was 2.32 microm, whereas with concentrations of 20 and 100 microl/ml TL were 12.47 and 42.3 microm, respectively. TM of control cultures was 0.18, whereas with vaccine concentrations of 20 and 100 microl/ml TM were 5.52 and 24.52, respectively. Comet frequency distributions differed significantly among treatments. These results agree with previous in vivo observations. Regarding CSF pathogeny, our results support a direct effect of CSF vaccinal virus on lymphocyte DNA. Genotoxicity of CSF vaccine was corroborated in vitro at the cytogenetic and molecular levels.

Animals↗

Differences of circulating Bordetella pertussis population in Argentina from the strain used in vaccine production.

In Argentina, as in other countries, the number of pertussis cases has been increasing, even in highly vaccinated zones. Many reports suggest that the decline of vaccine efficacy due to antigenic shifts in the circulating Bordetella pertussis might be among the factors that contribute to pertussis re-emergence in different parts of the world. To evaluate the incidence of this factor in Argentina, we decided to characterize the circulating bacteria of an important demographic area of this country in comparison with the strain used for vaccine production. From 1997 to 2003 we collected nasopharyngeal samples from pediatric patients with signs of Bordetella infection hospitalized in the metropolitan area of Buenos Aires and La Plata, Argentina. From these samples we identified 28 B. pertussis, which were characterized by biochemical techniques, PCR, DNA fingerprint, prn and ptx genes sequencing, and lipopolysaccharides (LPS) pattern. BOX-PCR from B. pertussis isolates yielded one cluster containing 13 isolates and some smaller ones, being all fingerprints different from the vaccine strain. Differences between Argentinean circulating bacteria and the vaccine strain were also observed for the Prn and Ptx variants as well as for the LPS pattern. Moreover, this last pattern seemed to change over the years. In addition, we identified two B. bronchiseptica. The presence of this Bordetella species together with the observed differences between circulating B. pertussis and the strain used in vaccine production should be considered for the development of an improved vaccine.

Adult↗

Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced DNA damage as shown by the comet assay technique.

Aloysia triphylla a perennial, bushy plant originally from South America has long been used in traditional medicine. Its aqueous extract contains considerable amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view of the interest in natural phenolic compounds as antioxidant in preventive medicine, this study was undertaken to investigate the chemoprotective effects of cedron leaves infusion against the genetic damage induced by acrylamide (AA) by using the alkaline version of the comet assay technique. Mice were separated in nine groups (eight animals each): (I) untreated, (II) negative control, (III) treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30 mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally evaluated per animal from three different slides (100 each). Media of tail moment (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were found between untreated animals, negative control and infusion-treated mice. A single dose of AA-induced genetic damage as revealed by a statistically significant increase in TM values (p<0.01). Pretreatment with infusion prior to AA injection significantly reduces the capacity of AA to induce genetic damage. In these conditions, tail moments values did not differ from data obtained in negative control (p>0.05) and exhibit statistical differences from animals treated only with AA (p<0.01). Cell viability was at least 90% in all cases as measured by the trypan blue exclusion method. The ferric reducing ability of plasma (FRAP) method reveals that the plasma of infusion-treated mice has a significantly higher antioxidant capacity than plasma from controls (p<0.01). The results suggest that the infusion could exerts an in vivo chemo protective action, probably due to its scavenging potency towards free radicals.

Acrylamide↗

A new method to estimate relatedness from molecular markers.

Four major problems can affect the efficiency of methods developed to estimate relatedness between individuals from information of molecular markers: (i) some of them are dependent on the knowledge of the true allelic frequencies in the base population; (ii) they assume that all loci are unlinked and in Hardy-Weinberg and linkage equilibrium; (iii) pairwise methods can lead to incongruous assignations because they take into account only two individuals at a time; (iv) most are usually constructed for particular structured populations (only consider a few relationship classes, e.g. full-sibs vs. unrelated). We have developed a new approach to estimate relatedness that is free from the above limitations. The method uses a 'blind search algorithm' (actually simulated annealing) to find the genealogy that yield a co-ancestry matrix with the highest correlation with the molecular co-ancestry matrix calculated using the markers. Thus (i and ii) it makes no direct assumptions about allelic frequencies or Hardy-Weinberg and linkage equilibrium; (iii) it always provide congruent relationships, as it considers all individuals at a time; (iv) degrees of relatedness can be as complex as desired just increasing the 'depth' (i.e. number of generations) of the proposed genealogies. Computer simulations have shown that the accuracy and robustness against genotyping errors of this new approach is comparable to that of other proposed methods in those particular situations they were developed for, but it is more flexible and can cope with more complex situations.

Algorithms↗

IgE antibodies to betalactams: relationship between the triggering hapten and the specificity of the immune response.

BACKGROUND: In immunoglobulin (Ig)E-mediated responses to betalactams (BL) the antibody is directed to the hapten inducing the response. For benzylpenicillin (BP) the determinant is benzylpenicilloyl (BPO) and for amoxicillin (AX), amoxicilloyl (AXO). Because of cross-reactivity, IgE from some patients reacts to both drugs whereas others have a drug-selective recognition. After an allergic episode, there is an increase in IgE that decreases over time. We analysed the response of patients allergic to BL after penicillin administration, with emphasis on IgE cross-reactivity. METHODS: Subjects who developed an IgE antibody response were studied. Sequential follow-up samples were obtained at different times during the response. Changes in IgE specificity were analysed by competition immunoassays using different penicillin monomeric conjugates. RESULTS: Two patterns of response were existed: one with IgE directed to the culprit penicillin and another with IgE mainly reactive to BPO. In both, a variable cross-reactivity with the hapten triggering the boosting response was found. This pattern was maintained with no change in specificity over time, even in subjects who experienced one boosting event. CONCLUSION: The IgE response can be specific to the drug inducing the reaction or cross-reactive to the classical BPO determinant. This pattern is maintained throughout the whole period of the response, even if re-exposure occurs. The stability of the type of response can be explained by the phenomenon of original antigenic sin: in the presence of antibodies, memory B cells are more easily triggered than naive B cells.

Antibody Specificity↗

Symmetry breaking in escaping ants.

The phenomenon of herding is a very general feature of the collective behavior of many species in panic conditions, including humans. It has been predicted theoretically that panic-induced herding in individuals confined to a room can produce a nonsymmetrical use of two identical exit doors. Here we demonstrate the existence of that phenomenon in experiments, using ants as a model of pedestrians. We show that ants confined to a cell with two symmetrically located exits use both exits in approximately equal proportions to abandon it in normal conditions but prefer one of the exits if panic is created by adding a repellent fluid. In addition, we are able to reproduce the observed escape dynamics in detail using a modification of a previous theoretical model that includes herding associated with a panic parameter as a central ingredient. Our experimental results, combined with theoretical models, suggest that some features of the collective behavior of humans and ants can be quite similar when escaping under panic.

Animal Feed↗

Genetic differentiation and estimation of effective population size and migration rates in two sympatric ecotypes of the marine snail Littorina saxatilis.

On exposed rocky shores in Galicia (northwest Spain), a striking polymorphism exists between two ecotypes (RB and SU) of Littorina saxatilis that occupy different levels of the intertidal zone and exhibit an incomplete reproductive isolation. The setting has been suggested to represent ongoing sympatric speciation by ecological adaptation of the two ecotypes to their respective habitats. In this article we address whether or not the ecotypes have developed their own population structures in response to the rigors of their corresponding environments and life histories. We analyzed four to five allozymic loci from three surveys of the same sites, spanning a 14-year period. An experimental design including three localities with two transects per locality and three shore levels allowed studying temporal and spatial population structure and estimation of effective population sizes (N(e)), neighborhood sizes (N(n)), and migration rates (m). Genetic differentiation was significantly lower in RB populations (theta(ST) = 0.067) than in SU ones (theta(ST) = 0.124). Mean estimates of N(e), N(n), and m did not differ significantly between ecotypes, but local ecotype differences in migration between the two closest localities (larger migration rates in RB than in SU populations) could explain the pattern in population differentiation.

Animals↗

Pho d 2, a major allergen from date palm pollen, is a profilin: cloning, sequencing, and immunoglobulin E cross-reactivity with other profilins.

BACKGROUND: Up to now, some date palm pollen (DPP) allergens have been described but very few data are available about their molecular nature. The aim of this study was to identify and characterize Pho d 2, a major allergen from this pollen. METHODS: Sera from 25 patients allergic to DPP were analysed by immunoblotting. Purification of DPP profilin was performed by poly-l-proline affinity chromatography. Profilin-encoding cDNA from DPP was cloned by using a RT-PCR strategy and recombinant allergen was expressed as a non-fusion protein in Escherichia coli. Natural and recombinant Pho d 2 were investigated by means of enzyme allergosorbent test to compare the immunologic properties of both allergens and to analyse cross-reactivity with other profilins. RESULTS: A 14.4 kDa protein was identified as a major allergen in DPP extract. Purification, cloning, heterologous expression, and inhibition experiments identified it as profilin (Pho d 2). Pho d 2 comprises 131 amino acids and has high sequence identity with other allergenic food and pollen profilins. The prevalence of specific IgE antibody reactivity to natural Pho d 2 by ELISA was 56% and 64% by skin prick test (SPT). Pho d 2 is an important allergen as it is responsible for more than 70% of the IgE reactivity to the pollen extract. IgE directed against Pho d 2 showed a strong cross-reactivity with other profilins such as those from olive tree and grass pollens. CONCLUSION: Pho d 2, a 14.4 kDa protein identified as profilin, is a major and relevant allergen in DPP, as confirmed by SPT and thereby may elicit clinical symptoms in sensitized patients.

Adult↗

Effects of addition of policosanol to omega-3 fatty acid therapy on the lipid profile of patients with type II hypercholesterolaemia.

BACKGROUND: Policosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol. OBJECTIVE: To investigate whether combined therapy with omega-3 FA + policosanol offers benefits compared with omega-3 FA + placebo with respect to the lipid profile of patients with type II hypercholesterolaemia. METHODS: This randomised, double-blind study was conducted in 90 patients with type II hypercholesterolaemia. After 5 weeks on a cholesterol-lowering diet, patients were randomised to omega-3 FA + placebo, omega-3 FA + policosanol 5 mg/day or omega-3 FA + policosanol 10 mg/day for 8 weeks. Omega-3 FA was supplied as 1g capsules (two per day); placebo and policosanol were provided in tablet form. Physical signs and laboratory markers were assessed at baseline and after 4 and 8 weeks on therapy. Drug compliance and adverse experiences (AEs) were assessed at weeks 4 and 8. The primary efficacy variable was LDL-C reduction; other lipid profile markers were secondary variables. RESULTS: After 8 weeks, omega-3 FA + policosanol 5 and 10 mg/day, but not omega-3 FA + placebo, significantly reduced LDL-C by 21.1% and 24.4%, respectively (both p < 0.0001). Omega-3 FA + policosanol 5 mg/day also significantly lowered TC (12.7%; p < 0.01) and TG (13.6%; p < 0.05), and significantly increased HDL-C (+14.4%; p < 0.001). Omega-3 FA + policosanol 10 mg/day significantly decreased TC (15.3%; p < 0.001) and TG (14.7%; p < 0.01), and significantly increased HDL-C (+15.5%; p < 0.0001). Omega-3 FA + placebo significantly reduced TG (14.2%; p < 0.05) but had no significant effect on other lipid profile variables. The proportion of randomised patients in the omega-3 FA + policosanol 5 or 10 mg/day groups that achieved LDL-C targets or reductions 15% was significantly greater than in the omega-3 FA + placebo group (p < 0.001). Combined therapy with omega-3 FA + policosanol 5 or 10 mg/day resulted in significantly greater changes in LDL-C, TC and HDL-C than treatment with omega-3 FA + placebo, but did not modify the TG response compared with the omega-3 FA + placebo group. Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group). CONCLUSIONS: Policosanol 5 or 10 mg/day administered concomitantly with omega-3 FA 1 g/day improved LDL-C, TC and HDL-C, maintained the reduction in TG attributable to omega-3 FA monotherapy, and was well tolerated. Treatment with omega-3 FA + policosanol could be useful for regulating lipid profile in patients with type II hypercholesterolaemia, but further studies involving larger sample sizes are needed before definitive conclusions can be drawn.

Aged↗

Benefits from marker-assisted selection under an additive polygenic genetic model.

This study investigated, through stochastic computer simulation, the extra gains expected from marker-assisted selection (MAS) in an infinitesimal model with linkage. The trait under selection was assumed to be controlled by 2,000 loci of additive small effect and evenly distributed in c chromosomes of one Morgan each (and c = 5, 10, 20, or 30). This approach differs from previous studies on the benefits of MAS that have considered mixed inheritance models. Marker information was used together with pedigree information to compute the relationship matrix used in BLUP genetic evaluations. The MAS schemes were compared with schemes where genetic evaluations were performed using standard BLUP (i.e., the relationship matrix is obtained using pedigree information only). When the number of markers was large enough (approximately one marker every 10 cM), there were increases in the accuracy of selection with MAS, and this led to extra gains compared with standard BLUP for all genome sizes considered. The benefit from MAS increased over generations. At the last generation of selection (Generation 10), the response from MAS was 11, 9, 7, and 5% greater than with standard BLUP for genomes with 5, 10, 20, and 30 chromosomes, respectively. Thus, although small, gains from MAS were nonetheless detectable for genome sizes typical of livestock populations.

Animal Husbandry↗

The effect of D-003 (10 mg/day) on biochemical parameters of bone remodelling in postmenopausal women: a randomized, double-blind study.

Biphosphonates, which are antiresorptive agents used to treat osteoporosis, inhibit the mevalonate pathway, preventing protein prenylation and inhibiting osteoclast activity. Statins decrease cholesterol biosynthesis by blocking the mevalonate pathway and have been reported to have beneficial effects on bone. D-003 is a mixture of high molecular weight acids purified from sugarcane wax that inhibits cholesterol biosynthesis before mevalonate production. D-003 prevents bone loss and resorption in rats with osteoporosis induced with ovariectomy or corticoids. Biochemical markers of bone turnover are used to monitor the short-term efficacy of antiosteoporotic therapy. This randomized, double-blind, placebo-controlled study was undertaken to investigate the short-term effects of D-003 (10 mg/day) on biochemical markers of bone turnover in postmenopausal women with low bone mineral density (BMD). After 4 weeks on a low-fat diet, 34 women were randomized to D-003 (10 mg/day) or placebo for 6 months. Pre- and post-treatment samples were analyzed for urinary excretion of deoxypyridinoline (DPD)/creatinine (Cr), a marker of bone resorption, and serum bone specific alkaline phosphatase (BSAP), a marker of bone formation. The effects on lipid profile and safety indicators, as well as adverse events (AE), were investigated. D-003 (10 mg/day) lowered urinary excretion of tDPD/Cr versus baseline (20.6%) (p < 0.001) and placebo (33.7%) (p < 0.01), but did not modify serum BSAP. D-003 decreased low-density lipoprotein-cholesterol (LDL-C) (32.8%), total cholesterol (TC) (16.4%) and the TC/high-density lipoprotein-cholesterol (HDL-C) ratio (34.7%), increased HDL-C (30.3%) (p < 0.001) and did not modify triglycerides. The effects on these variables were significant as early as 3 months after treatment initiation. D-003 was well tolerated. Three patients (one in the placebo group and two in the D-003 group) withdrew from the study. Two of these withdrawals were due to AE: abdominal pain (placebo) and heartburn (D-003). Five patients (four in the placebo group [22.2%] and one in the D-003 group [6.3%]) reported mild AE. In conclusion, D-003 (10 mg/day) reduced urinary excretion of tDPD/Cr, a bone resorption marker and did not change serum BSAP, a bone formation marker, while it lowered cholesterol in study patients. These preliminary results suggest that D-003 could be useful in treating postmenopausal women with low BMD. However, the potential value of D-003 in treating or preventing osteoporosis deserves further clinical investigation.

Alkaline Phosphatase↗

A comparison of the effects of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia: a randomized, double-blinded study.

The main goal of hypercholesterolemia management for coronary prevention is to reduce serum low-density lipoprotein cholesterol (LDL-C) levels. D-003 is a mixture of high molecular weight aliphatic acids purified from sugarcane wax, while policosanol is a cholesterol-lowering drug purified from the same source, consisting in a mixture of higher aliphatic alcohols. No previous comparative study of both drugs in humans has been reported. This randomized, double-blind study compares the efficacy and tolerability of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia. After a baseline period, 100 patients were randomized to D-003 or policosanol both at 5 mg/day and 10 mg/day, for 8 weeks. D-003 and policosanol 5 mg/day reduced (p < 0.0001) LDL-C by 26.9% and 20.9%, respectively. These reductions increased with 10 mg/day (35.1% for D-003, 25.1% for policosanol. The reductions of LDL-C achieved with D-003 5 mg/day and 10 mg/day were greater (p < 0.05 and p < 0.001, respectively) than with policosanol. The frequency of patients treated with D-003 (5 mg/day) reaching LDL-C reductions > or = 15% (22/25, 88%) was greater (p < 0.01) than with policosanol (5 mg/day) (19/25, 76%), and the same was true for D-003 10 mg/day (25/25, 100%) and policosanol (22/25, 88%; p < 0.01). D-003 and policosanol (5 mg/day) also lowered (p < 0.001) total cholesterol (TC) (16.2% and 13.5%, respectively), and increased high-density lipoprotein cholesterol (HDL-C) by 15.3% (D-003) and 6.7% (policosanol). At 10 mg/day, D-003 and policosanol reduced (p < 0.001) TC (21.3% and 16.0%, respectively), while HDL-C was increased by 17.3% and 9.8%, respectively, D-003 being more effective than policosanol. Treatments did not affect triglycerides. Both drugs were well tolerated, with D-003 tolerated as well as policosanol. Three patients discontinued the study, none due to adverse events (AEs). Seven patients (three from the D-003 group and four from the policosanol group) experienced mild AEs. In conclusion, D-003 (5 and 10 mg/day) administered to patients with type II hypercholesterolemia was more effective than policosanol in lowering LDL-C and TC, and in increasing HDL-C. D-003 could be useful for treating type II hypercholesterolemia, but this subject deserves further clinical research.

Aged↗

Ultralow emittance, multi-MeV proton beams from a laser virtual-cathode plasma accelerator.

The laminarity of high-current multi-MeV proton beams produced by irradiating thin metallic foils with ultraintense lasers has been measured. For proton energies >10 MeV, the transverse and longitudinal emittance are, respectively, <0.004 mm mrad and <10(-4) eV s, i.e., at least 100-fold and may be as much as 10(4)-fold better than conventional accelerator beams. The fast acceleration being electrostatic from an initially cold surface, only collisions with the accelerating fast electrons appear to limit the beam laminarity. The ion beam source size is measured to be <15 microm (FWHM) for proton energies >10 MeV.

Journal Article↗