Search PubMed⌕ Search

Biomedical subjects

A Salas

Publications and source records attributed to A Salas.

At least 19 recordsLinked to original sources
PubMed2007

A bidirectional corridor in the Sahel-Sudan belt and the distinctive features of the Chad Basin populations: a history revealed by the mitochondrial DNA genome.

The Chad Basin was sparsely inhabited during the Stone Age, and its continual settlement began with the Holocene. The role played by Lake Chad in the history and migration patterns of Africa is still unclear. We studied the mitochondrial DNA (mtDNA) variability in 448 individuals from 12 ethnically and/or economically (agricultural/pastoral) different populations from Cameroon, Chad, Niger and Nigeria. The data indicate the importance of this region as a corridor connecting East and West Africa; however, this bidirectional flow of people in the Sahel-Sudan Belt did not erase features peculiar to the original Chad Basin populations. A new sub-clade, L3f2, is described, which together with L3e5 is most probably autochthonous in the Chad Basin. The phylogeography of these two sub-haplogroups seems to indicate prehistoric expansion events in the Chad Basin around 28,950 and 11,400 Y.B.P., respectively. The distribution of L3f2 is virtually restricted to the Chad Basin alone, and in particular to Chadic speaking populations, while L3e5 shows evidence for diffusion into North Africa at about 7,100 Y.B.P. The absence of L3f2 and L3e5 in African-Americans, and the limited number of L-haplotypes shared between the Chad Basin populations and African-Americans, indicate the low contribution of the Chad region to the Atlantic slave trade.

Chad↗
PubMed2007

Influence of the type of pegylated interferon on the onset of depressive and neuropsychiatric symptoms in HIV-HCV coinfected patients.

This is a prospective observational comparative 48-week study to assess the impact of the different types of Peg-IFN on depressive and neuropsychiatric symptoms during treatment in HIV-HCV coinfected patients. Thirty-one patients treated with Peg-IFN alpha-2b 1.5 microg/kg/w plus ribavirine (RBV) (Peg-IFN alpha-2b Group) and 32 patients receiving Peg-IFN alpha-2a 180 microg/w plus RBV (Peg-IFN alpha-2a Group) were included. Depressive and neuropsychiatric symptoms, quality of life and adherence were assessed. Fifteen subjects (23%) discontinued therapy (p = 0.3, between groups). Overall, 37 patients presented mild to moderate depressive symptoms, 9 moderate to severe and 3 severe, without differences between groups. Patients in Peg-IFN alpha-2b reported higher fatigue and dizziness at weeks 12 (p < 0.05) and 24 (p < 0.05), and irritability and memory loss at week 24 (p < 0.05) with respect to Peg-IFN alpha-2a Group. At week 12, role functioning, general health perception, vitality, emotional role, mental health and the summary areas of physical health and mental health were lower in Peg-IFN alpha-2b Group (p < 0.05). The same was observed in physical functioning (p = 0.05) and role functioning, general health perception, emotional role and mental health (p < 0.001) at week 24. Three months after finishing treatment, no patient had depressive or neuropsychiatric symptoms, and quality of life improved. Antiretroviral adherence was low but adherence to anti-HCV therapy remained high in both groups. According to our data, Peg-IFN alpha-2a and Peg-IFN alpha-2b exert a similar impact on the overall rate of depressive symptoms, although patients treated with Peg-IFN alpha-2a experience less fatigue and fewer neuropsychiatric symptoms and a lower impairment in their physical and mental quality of life.

Adult↗
PubMed2006

Analysis of body fluid mixtures by mtDNA sequencing: An inter-laboratory study of the GEP-ISFG working group.

The mitochondrial DNA (mtDNA) working group of the GEP-ISFG (Spanish and Portuguese Group of the International Society for Forensic Genetics) carried out an inter-laboratory exercise consisting of the analysis of mtDNA sequencing patterns in mixed stains (saliva/semen and blood/semen). Mixtures were prepared with saliva or blood from a female donor and three different semen dilutions (pure, 1:10 and 1:20) in order to simulate forensic casework. All labs extracted the DNA by preferential lysis and amplified and sequenced the first mtDNA hypervariable region (HVS-I). Autosomal and Y-STR markers were also analysed in order to compare nuclear and mitochondrial results from the same DNA extracts. A mixed stain prepared using semen from a vasectomized individual was also analysed. The results were reasonably consistent among labs for the first fractions but not for the second ones, for which some laboratories reported contamination problems. In the first fractions, both the female and male haplotypes were generally detected in those samples prepared with undiluted semen. In contrast, most of the mixtures prepared with diluted semen only yielded the female haplotype, suggesting that the mtDNA copy number per cell is smaller in semen than in saliva or blood. Although the detection level of the male component decreased in accordance with the degree of semen dilution, it was found that the loss of signal was not consistently uniform throughout each electropherogram. Moreover, differences between mixtures prepared from different donors and different body fluids were also observed. We conclude that the particular characteristics of each mixed stain can deeply influence the interpretation of the mtDNA evidence in forensic mixtures (leading in some cases to false exclusions). In this sense, the implementation of preliminary tests with the aim of identifying the fluids involved in the mixture is an essential tool. In addition, in order to prevent incorrect conclusions in the interpretation of electropherograms we strongly recommend: (i) the use of additional sequencing primers to confirm the sequencing results and (ii) interpreting the results to the light of the phylogenetic perspective.

Blood↗
PubMed2006

Phylogeographic investigations: the role of trees in forensic genetics.

The human mitochondrial DNA (mtDNA) genome is commonly analyzed in various disciplines, such as population, medical, and forensic genetics, but conceptual and scientific exchange between them is still limited. Here we review several aspects of the mtDNA phylogeny that are particularly--but not exclusively--of interest to the forensic community. Among the issues that arise, we emphasize the importance of integrating evolutionary concepts into the forensic routine. We also discuss topics such as mtDNA mutation-rate heterogeneity and the weight of evidence, ethnic affiliations of mtDNA profiles, and the abuse of reference databases. Finally, we show the usefulness of coding-region variation in a forensic context.

DNA Fingerprinting↗
PubMed2006

Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

BACKGROUND: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. AIMS: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. PATIENTS AND METHODS: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. RESULTS: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II-III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p = 0.002). Marsh I relatives had more severe abdominal pain (p = 0.006), severe distension (p = 0.047) and anaemia (p = 0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). CONCLUSIONS: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Adolescent↗
PubMed2006

Weight loss with long-term intermittent treatment with oral oleoyl-estrone in lean Zucker male rats.

To determine whether or not the long-term intermittent treatment with oleoyl-estrone (OE) in rats induces a cumulative weight loss, adult male rats were treated with OE over three alternating 10-day periods, with a 30-day "recovery" period occurring between each period. At the end of the third treatment period, the rats were allowed to recover and were then mated with females. Each treatment period produced a decrease of ca. 7% in body weight with no rebound during the recovery periods, whereas weight changed at the same pace in controls. The greatest difference in body weight was observed during the last days of treatment. OE-treated rats retained their initial protein pools throughout the treatment. Furthermore, treated and control males remained fertile and were able to procreate. Thus, we can conclude that intermittent OE treatment induces a cumulative weight loss in adult male rats.

Adipose Tissue↗
PubMed2005

Selective inhibition of phosphodiesterase-4 ameliorates chronic colitis and prevents intestinal fibrosis.

The phosphodiesterase-4 (PDE4) inhibitors may be an important target in the treatment of several inflammatory conditions. The anti-inflammatory effect of PDE4 inhibitors bears similarities with that of steroids, without interfering with the hypophysary-adrenal-axis. We compared the effect of rolipram, a selective PDE4 inhibitor, with steroids on the clinical course of experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Three groups of rats (n = 20) received TNBS. One group received methylprednisolone from day 7, another group received rolipram from the same day, and control group received no further treatment. On days 14 and 21 after TNBS instillation, sets of 10 rats underwent colonic dialysis to measure eicosanoid release. Colonic lesions were blindly scored, and colons were homogenized for quantification of myeloperoxidase (MPO) activity and collagen content. Concentration of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) in colonic tissue was also measured. Both treatments reduced significantly the eicosanoid release and MPO activity. On day 14, both rolipram and methylprednisolone significantly reduced TNF-alpha content, but TGF-beta1 was only inhibited by rolipram. On day 21, lesion scores and collagen content were significantly reduced only in rolipram-treated group. In conclusion, PDE4 inhibition by rolipram markedly ameliorates the course of chronic colitis and it is superior to methylprednisolone in preventing late collagen deposition.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

More evidence for non-maternal inheritance of mitochondrial DNA?

BACKGROUND: A single case of paternal co-transmission of mitochondrial DNA (mtDNA) in humans has been reported so far. OBJECTIVE: To find potential instances of non-maternal inheritance of mtDNA. METHODS: Published medical case studies (of single patients) were searched for irregular mtDNA patterns by comparing the given haplotype information for different clones or tissues with the worldwide mtDNA database as known to date-a method that has proved robust and reliable for the detection of flawed mtDNA sequence data. RESULTS: More than 20 studies were found reporting clear cut instances with mtDNAs of different ancestries in single individuals. As examples, cases are reviewed from recent published reports which, at face value, may be taken as evidence for paternal inheritance of mtDNA or recombination. CONCLUSIONS: Multiple types (or recombinant types) of quite dissimilar mitochondrial DNA from different parts of the known mtDNA phylogeny are often reported in single individuals. From re-analyses and corrigenda of forensic mtDNA data, it is apparent that the phenomenon of mixed or mosaic mtDNA can be ascribed solely to contamination and sample mix up.

DNA, Mitochondrial↗
PubMed2005

Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat.

OBJECTIVE: Oral treatment with oleoyl-estrone induces the loss of body fat and improvement of insulin resistance. Since cholesterol levels are deeply affected by oleoyl-estrone, we investigated here whether short-term treatment affected cholesterol turnover and overall metabolite changes. DESIGN: Wistar female rats received a single oral dose of 10 mumol/kg oleoyl-estrone in 0.2 ml of sunflower oil. Groups of animals were killed at timed intervals and blood samples were taken. In a second experiment series, rats had implanted carotid and jugular cannulas and were given a single gavage of oleoyl-estrone. These rats were used for the measurement of the cholesterol turnover rate. MEASUREMENTS: Body weight change and food intake: Glucose, total and HDL-cholesterol, triacylglycerols, 3-hydroxybutyrate, nonesterified fatty acids, insulin, HOMA score in the rats of the first series. Cholesterol: Cholesterol pool changes and cholesterol turnover rates in the rats of the second series. RESULTS: OE induced early effects, decreasing food intake, cholesterol and HDL-cholesterol levels, and increasing insulin sensitivity (HOMA score). OE also increased cholesteryl-ester turnover, and decreased circulating total cholesterol, especially esterified cholesterol pools. CONCLUSIONS: The role of early changes in insulin sensitivity induced by oral OE cannot explain per se the deep changes in cholesterol handling, essentially a consequence of accelerated lipoprotein turnover. However, the increase in cholesteryl-ester turnover observed with OE treatment may be, at least in part, a consequence of the decrease in insulin resistance. The compounded effect of increased insulin sensitivity and accelerated lipoprotein turnover may help explain the early and marked hypocholesterolaemic effects of OE.

Administration, Oral↗
PubMed2005

Mucosal colonisation with Lactobacillus casei mitigates barrier injury induced by exposure to trinitronbenzene sulphonic acid.

BACKGROUND: Trinitrobenzene sulphonic acid (TNBS) induces chronic transmural inflammatory lesions in the rat colon. Injury is facilitated by barrier disruption and invasion of commensal bacteria. However, certain bacteria have shown anti-inflammatory properties in in vitro models. AIM: To investigate in vivo the anti-inflammatory effect of Lactobacillus casei DN-114 001. METHODS: Rats with a colonic segment excluded from faecal transit were surgically prepared. After washing the lumen with antibiotics, the excluded segment was recolonized (control group: standard flora of rat origin; test group: standard flora and L casei). Microbial colonisation was confirmed by culture of segment washing, and colitis was then induced by instillation of TNBS. One day after, intestinal lesions were blindly graded by macro- and microscopic scores, and myeloperoxidase activity measured in tissue homogenates. Translocation of bacteria to mesenteric lymph nodes, spleen and liver was investigated. RESULTS: Test rats showed a smaller area of mucosal injury than control rats (p<0.05). Maximum depth lesion scores were similar in both groups but myeloperoxidase activity was lower in test than in control rats (p<0.05). Remarkably, bacterial translocation was quantitatively lower (p<0.01) and less frequent (p<0.05) in test than in control rats. CONCLUSION: In rats colonised with L casei, mucosal injury, inflammatory response, and barrier disruption after TNBS challenge were attenuated. Bacterial communities colonising the mucosa can modify inflammatory responses to luminal challenges.

Animals↗
PubMed2004

Typing of mitochondrial DNA coding region SNPs of forensic and anthropological interest using SNaPshot minisequencing.

The development of new methodologies for high-throughput SNP analysis is one of the most stimulating areas in genetic research. Here, we describe a rapid and robust assay to simultaneously genotype 17 mitochondrial DNA (mtDNA) coding region SNPs by minisequencing using SNaPshot. SNaPshot is a methodology based on a single base extension of an unlabeled oligonucleotide with labeled dideoxy terminators. The set of SNPs implemented in this multiplexed SNaPshot reaction allow us to allocate common mitochondrial West Eurasian haplotypes into their corresponding branch in the mtDNA skeleton, with special focus on those haplogroups lacking unambiguous diagnostic positions in the first and second hypervariable regions (HVS-I/II; by far, the most common segments analyzed by sequencing). Particularly interesting is the set of SNPs that subdivide haplogroup H; the most frequent haplogroup in Europe (40-50%) and one of the most poorly characterized phylogenetically in the HVS-I/II region. In addition, the polymorphic positions selected for this multiplex reaction increase considerably the discrimination power of current mitochondrial analysis in the forensic field and can also be used as a rapid screening tool prior to full sequencing analysis. The method has been validated in a sample of 266 individuals and shows high accuracy and robustness avoiding both the use of alternative time-consuming classical strategies (i.e. RFLP typing) and the need for high quantities of DNA template.

DNA Primers↗
PubMed2004

Results of a collaborative study of the EDNAP group regarding mitochondrial DNA heteroplasmy and segregation in hair shafts.

A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in order to evaluate the distribution of mitochondrial DNA (mtDNA) heteroplasmy amongst the hairs of an individual who displays point heteroplasmy in blood and buccal cells. A second aim of the exercise was to study reproducibility of mtDNA sequencing of hairs between laboratories using differing chemistries, further to the first mtDNA reproducibility study carried out by the EDNAP group. Laboratories were asked to type 2 sections from each of 10 hairs, such that each hair was typed by at least two laboratories. Ten laboratories participated in the study, and a total of 55 hairs were typed. The results showed that the C/T point heteroplasmy observed in blood and buccal cells at position 16234 segregated differentially between hairs, such that some hairs showed only C, others only T and the remainder, C/T heteroplasmy at varying ratios. Additionally, differential segregation of heteroplasmic variants was confirmed in independent extracts at positions 16093 and the poly(C) tract at 302-309, whilst a complete A-G transition was confirmed at position 16129 in one hair. Heteroplasmy was observed at position 16195 on both strands of a single extract from one hair segment, but was not observed in the extracts from any other segment of the same hair. Similarly, heteroplasmy at position 16304 was observed on both strands of a single extract from one hair. Additional variants at positions 73, 249 and the HVII poly(C) region were reported by one laboratory; as these were not confirmed in independent extracts, the possibility of contamination cannot be excluded. Additionally, the electrophoresis and detection equipment used by this laboratory was different to those of the other laboratories, and the discrepancies at position 249 and the HVII poly(C) region appear to be due to reading errors that may be associated with this technology. The results, and their implications for forensic mtDNA typing, are discussed in the light of the biology of hair formation.

DNA, Mitochondrial↗
PubMed2004

Analysis of the vitamin D receptor Fokl polymorphism.

In the present study we analysed the vitamin D receptor (VDR) Fokl polymorphism distribution in a Caucasian population from the North-West of Spain. This polymorphism has been associated with variation in bone mineral density levels and has been proposed as a factor for the genetic predisposition to osteoporosis. This study was performed in 60 healthy individuals by restriction fragment length polymorphism (RFLP) analysis using the endonuclease Fokl and alternatively using single strand conformation polymorphism (SSCP). The genotype distribution was: 46.7% FF homozygotes, 43.3% Ff heterozygotes, and 10% ff homozygotes. These values do not reveal significant differences in comparison with other available Caucasoid populations, but show clear differences with respect to African-American populations. The analysis of this polymorphism by SSCP reveals the existence of a novel single nucleotide polymorphism (AAT/AAC) located within the DNA binding domain of the VDR gene at position-19 codon. Thus, using a novel 109 bp hVDR gene fragment which excludes the AAT/AAC variant in the vitamin D receptor Fokl allows an easier determination by SSCP analysis of the Fokl polymorphism.

Adult↗
PubMed2004

Artificial recombination in forensic mtDNA population databases.

Artificial recombination of two or more mitochondrial DNA fragments from different samples would constitute a serious cause of error in forensic DNA typing, and yet one can demonstrate that such events have happened in the preparation of several published mtDNA databases. Focussed database searches, phylogenetic analysis, and network representations can highlight mosaic patterns and thus pinpoint sample mix-up. Therefore, we suggest that this approach should be applied to data prior to publication in order to uncover such errors in time.

DNA Fingerprinting↗
PubMed2004

Inferring the most likely geographical origin of mtDNA sequence profiles.

In a number of practical cases it is important to determine the likely geographical origin of an individual or a biological sample. A dead body, old bones or a sample of semen may be available. Information on where the sample might come from can assist investigation or research. The first part of this paper is independent of specific data structure. We formulate the problem as a classification problem. Bayes' theorem allows different sources of information or data to be reconciled conveniently. The main part of the paper involves high dimensional data for which simple, standard methods are not likely to work properly. Mitochondrial DNA (mtDNA) data is a typical example of such data. We propose a procedure involving essentially two steps. First, principal component analysis is used to reduce the dimension of the data. Next, quadratic discriminant analysis performs the actual classification. A cross validation procedure is implemented to select the optimal number of principal components. The importance of using separate data sets for model fitting and testing is emphasized. This method distinguishes well between individuals with a self reported European (Icelandic or German) origin and SE Africans. In this case the error rate is 2.0%.

Africa↗
PubMed2003

Population study of eight novel Y-chromosome STRs (DYS460, DYS461, GATA-A10, GATA-C4, GATA-H4, DYS434, DYS437, DYS439) in a southeast Iberian population: looking for highly informative Y-chromosome haplotypes.

The present study analyses 8 recently described tetranucleotide microsatellites (DYS460, DYS461, GATA-A10, GATA-C4, GATA-H4, DYS434, DYS437, DYS439) in southeast Spain and out of a total of 76 individuals 67 showed different haplotypes. Out of the 67 different haplotypes, 63 were present once, 3 were found 2 times, and 1 was found 7 times (9.21%). By combining the allelic states of the present eight Y-chromosome STRs with those previously carried out on the same individuals, highly informative haplotypes could be obtained. The haplotype diversity using the basic set of Y-STRs (DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, DYS385 and DYX156Y) previously analyzed is 0.9844. For the same individuals, this value using the new set of Y-STRs is slightly lower (0.8949), while the haplotype diversity combining the two sets of primers significantly increase to 0.9868. The results obtained in the present work show the usefulness of these microsatellites for individual identification and paternity testing in forensic genetics.

Chromosomes, Human, Y↗
PubMed2003

Insights into Iberian population origins through the construction of highly informative Y-chromosome haplotypes using biallelic markers, STRs, and the MSY1 minisatellite.

To investigate the diversity of Y chromosomes in the Iberian Peninsula and the North African population of Maghreb, we constructed superhaplotypes on the basis of 10 biallelic markers, 7 microsatellites, and 1 minisatellite located in the nonrecombining portion of the human Y chromosome. The analysis of extremely high MSY1 variability was performed by reducing the MVR-codes to modular structures. Y-STRs and MSY1 data provide information about the relationship between closely related populations such as those of Iberia. Analysis of biallelic markers allowed us to identify 7 of 12 haplogroups defined by those polymorphisms. The haplogroup background showed clear differences between Iberian populations and the North African one. The use of differently mutating Y-chromosome markers allowed us to infer different population events at different time scales: the Paleolithic background of the Iberian Peninsula, the Neolithic fingerprint on Y-chromosome lineages, and the Iron Age influence in the populations of Iberia. Implications of our results for the highly debated origin of Basques are also discussed.

Black People↗