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Biomedical subjects

V Fernández

Publications and source records attributed to V Fernández.

At least 19 recordsLinked to original sources
PubMed2005

Scientific management of Mediterranean coastal zone: a hybrid ocean forecasting system for oil spill and search and rescue operations.

The oil spill from Prestige tanker showed the importance of scientifically based protocols to minimize the impacts on the environment. In this work, we describe a new forecasting system to predict oil spill trajectories and their potential impacts on the coastal zone. The system is formed of three main interconnected modules that address different capabilities: (1) an operational circulation sub-system that includes nested models at different scales, data collection with near-real time assimilation, new tools for initialization or assimilation based on genetic algorithms and feature-oriented strategic sampling; (2) an oil spill coastal sub-system that allows simulation of the trajectories and fate of spilled oil together with evaluation of coastal zone vulnerability using environmental sensitivity indexes; (3) a risk management sub-system for decision support based on GIS technology. The system is applied to the Mediterranean Sea where surface currents are highly variable in space and time, and interactions between local, sub-basin and basin scale increase the non-linear interactions effects which need to be adequately resolved at each one of the intervening scales. Besides the Mediterranean Sea is a complex reduced scale ocean representing a real scientific and technological challenge for operational oceanography and particularly for oil spill response and search and rescue operations.

Disaster Planning↗
PubMed2005

Checkpoint kinase 1 (CHK1) protein and mRNA expression is downregulated in aggressive variants of human lymphoid neoplasms.

CHK1: gene encodes for a serine/threonine kinase involved in the regulation of cell cycle progression and DNA damage checkpoints. To determine the role of CHK1 in the pathogenesis of lymphoid neoplasms and its relationship to other DNA damage response genes, we have analyzed the gene status, protein, and mRNA expression in a series of tumors and nonneoplastic lymphoid tissues. CHK1 protein and mRNA expression levels were very low in both reactive tissues and resting lymphoid cells, whereas tumor samples showed a variable pattern of expression related to their proliferative activity. However, seven aggressive tumors showed a dissociate pattern of extremely low or negative protein expression in spite of a high proliferative activity. Four of these tumors were diffuse large B-cell lymphomas (DLCLs) with concordant reduced levels of mRNA, whereas one blastoid mantle cell lymphoma (B-MCL) and two DLCLs had relatively normal levels of mRNA. No gene mutations, deletions, or hypermethylation of the promoter region were detected in any of these cases. In all these tumors ATM, CHK2, and p53 genes were wild type. These findings suggest that CHK1 inactivation in NHLs occurs by loss of protein expression in a subset of aggressive variants alternatively to ATM, CHK2, and p53 alterations.

Blotting, Western↗
PubMed2005

HLA class II and response to interferon-beta in multiple sclerosis.

OBJECTIVE: To study the relationship between human leucocyte antigen (HLA) genotype and clinical response to interferon-beta (IFN-beta). METHODS: We analysed the HLA class II genotypes of 96 multiple sclerosis (MS) patients treated with IFN-beta. The patients were classified as responders or non-responders according to clinical criteria: one or more relapses or a sustained increase after 1 year treatment compared with the year prior to IFN-beta therapy of > or = 0.5 points on the Expanded Disability Status Scale (EDSS). RESULTS: There were 66 (69%) responders and 30 (31%) non-responders. Baseline clinical characteristics were similar. We found no association between HLA class II alleles and clinical response to IFN-beta. CONCLUSIONS: HLA genotype does not appear to influence the clinical response to IFN-beta in MS patients.

Adult↗
PubMed2005

Increased immunohistochemical expression of thrombomodulin at placental perivascular myofibroblast in severe preeclampsia (PE).

The presence of pro-coagulant and anti-coagulant components of the placental vascular endothelium and syncytiotrophoblast are essential for homeostasis. Vascular endothelium prevents blood clot formation in vivo by involving a cell surface thrombin-binding glycoprotein, thrombomodulin (TM), that activates plasma anti-coagulant protein C. The TM levels increase during pregnancy, but the fibrinolytic capacity diminishes. Since vascular lesions with placental coagulation disorders can be associated with preeclampsia (PE), we hypothesized that TM expression in the stem villous vasculature and syncytiotrophoblast of the placenta are impaired in PE. Plasma and placental tissue samples were collected from PE (n=12) and normotensive pregnant patients (n=11). Patient's gestational age was 35.7+/-1.2 (normotensive) and 30.6+/-1.5 weeks (PE). Blood samples were drawn 30 min before delivery. Serum PAI-1 and PAI-2 antigens were determined by enzyme-linked immunoabsorbent assay (ELISA). A monoclonal antibody specific for TM was used for immunohistochemical tissue staining (ABC) and the staining was quantified by semi quantitative scores. Results show no intensity differences at the apical syncytiotrophoblast between the two groups. However, in preeclamptic placenta, TM expression diminished in the endothelium of the stem villi arteries and increased in the perivascular and stromal myofibroblats in cases of severe PE. TM changes were associated with an increased PAI-1/PAI-2 ratio. It is suggested that in severe PE, the decreased placental blood flow may be due to structural and functional impairment of the endothelium of the stem villi vessels and the surrounding perivascular and stromal myofibroblast, by increasing TM expression which may modulate fetal blow flow in the villous tree.

Actins↗
PubMed2004

Azathioprine and methotrexate in multiple sclerosis.

Evidence for the effectiveness of immunosuppressive agents in MS is scanty. There are few good quality trials; most have methodological limitations, such as a small sample size and short duration. Moreover, there is no consistency in treatment regimes, patient groups or outcome measures and the clinical benefits remain unclear. Although azathioprine appears to reduce the relapse rate in MS patients, its effect on disability progression has not been demonstrated. Methotrexate may alter the course of disease favourably in patients with progressive MS, but the evidence is again sparse.

Azathioprine↗
PubMed2004

DQB1*0602 allele shows a strong association with multiple sclerosis in patients in Malaga, Spain.

BACKGROUND: The human leukocyte antigen (HLA) class II DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) has been associated with multiple sclerosis (MS) in all ethnic groups and very strongly in Caucasians. AIM: To investigate the possible HLA class II (DRB1, DQA1 and DQB1) associations with MS in Malaga, southern Spain. METHODS: We analysed the HLA class II sub-regions DRB1, DQA1 and DQB1 by polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe hybridization (PCR/SSO) for DRB1 and DQB1 and with sequence-specific primers (PCR/SSP) for DRB1 subtypes and DQA1. Possible HLA class II associations with clinical MS characteristics were investigated in 149 subjects with and 160 without MS. RESULTS: Associations were detected between MS and the HLA class II alleles DRB1*1501 (45.6 % vs. 21.3%, p=0.001), DQA1*0102 (44% vs. 29.4%, p=0.001) and DQB1*0602 (45% vs. 20.6%, p=0.001). The DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) was associated with MS (43.6 % vs. 20%, p=0.002). DQB1*0602 was the only allele that maintained an association with MS in a logistic regression model. No HLA class II alleles or genotypes were significantly associated with any clinical characteristics of MS. CONCLUSIONS: Our results confirm the positive association of the DR2 haplotype with MS, particularly the allele DQB1*0602, in the population studied. DR4 was not associated with the disease in Malaga. HLA class II alleles or haplotypes were not associated with clinical or demographic characteristics, or clinical form or severity of MS.

Adolescent↗
PubMed2004

Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

Adolescent↗
PubMed2004

The effect of expression levels on codon usage in Plasmodium falciparum.

The usage of alternative synonymous codons in the completely sequenced, extremely A+T-rich parasite Plasmodium falciparum was studied. Confirming previous studies obtained with less than 3% of the total genes recently described, we found that A- and U-ending triplets predominate but translational selection increases the frequency of a subset of codons in highly expressed genes. However, some new results come from the analysis of the complete sequence. First, there is more variation in GC3 than previously described; second, the effect of natural selection acting at the level of translation has been analysed with real expression data at 4 different stages and third, we found that highly expressed proteins increment the frequency of energetically less expensive amino acids. The implications of these results are discussed.

Animals↗
PubMed2003

Myoglobinuria and COX deficiency in a patient taking cerivastatin and gemfibrozil.

The authors describe a patient who presented with myoglobinuria after starting cerivastatin-gemfibrozil therapy. Muscle histochemistry revealed ragged-red fibers and cytochrome c oxidase negative (COX) fibers, and biochemistry showed a defect of COX activity. Immunoblot analysis showed a 60% reduction of COX I and COX II polypeptides. Cerivastatin myotoxicity might be related to a depletion of essential metabolites needed to anchor COX subunit I to mitochondrial membrane.

Aged↗
PubMed2002

Influence of C-phycocyanin on hepatocellular parameters related to liver oxidative stress and Kupffer cell functioning.

OBJECTIVES: Kupffer cells, liver macrophages involved in immunomodulation, phagocytosis, and biochemical attack, can induce cytotoxicity and inflammation when their activity is exacerbated. The aim of this study was to evaluate the effects of C-phycocyanin on Kupffer cell functioning considering its antioxidant and anti-inflammatory properties. MATERIALS AND METHODS: Actions of C-phycocyanin on colloidal carbon phagocytosis, carbon-induced respiratory burst activity, and sinusoidal lactate dehydrogenase (LDH) release were studied in isolated perfused mouse liver. The influence of C-phycocyanin on tumor necrosis factor-a (TNF-alpha) and nitrite levels in serum and liver nitric oxide synthase (NOS) activity was assessed in rats subjected to thyroid hormone (T3) administration, a condition known to underlie hepatic oxidative stress comprising an increased Kupffer cell activity. RESULTS: C-phycocyanin elicited a concentration-dependent inhibition of carbon phagocytosis and carbon-induced O2 uptake (IC50 = 0.2 mg/ml) by perfused livers, with a 52% diminution in the carbon-induced sinusoidal release of LDH being found at a concentration of 0.25 mg/ml. Thyroid calorigenesis induced an 82-fold increase in serum TNF-alpha levels, an effect that was suppressed by pretreatment with C-phycocyanin, the antioxidant alpha-tocopherol, and by the Kupffer cell inactivator gadolinium chloride. C-phycocyanin also suppressed the T3-induced increases in serum nitrite levels (234%) and in the activity of hepatic NOS (75%). CONCLUSIONS: C-phycocyanin significantly decreases Kupffer cell phagocytosis and the associated respiratory burst activity, effects that may contribute to the abolition of oxidative stress-induced TNF-alpha response and NO production by hyperthyroid state.

Animals↗
PubMed2001

Iron-induced changes in nitric oxide and superoxide radical generation in rat liver after lindane or thyroid hormone treatment.

The involvement of cytosolic nitric oxide (NO) and mitochondrial superoxide radical (O2(.-)) production was evaluated as a mechanism triggering liver oxidative stress in lindane (40 mg/kg) or L-3,3',5-triiodothyronine (T3, 0.1 mg/kg for 2 consecutive days) treated animals (male Sprague-Dawley rats) subjected to iron overload (200 mg/kg). Lindane and iron led to 504 and 210% increases in the content of hepatic protein carbonyls as an index of oxidative stress, with a 706% enhancement being produced by their combined administration. T3 did not alter this parameter, whereas iron overload increased the content of protein carbonyls by 116% in hyperthyroid rats. Lindane increased NO generation by 106% without changes in generation of O2(.-), whereas iron enhanced both parameters by 109 and 80% over control values, respectively, with a net 33 and 46% decrease, respectively, being elicited by the combined treatment related to iron overload alone. Hyperthyroidism increased liver NO (69%) and O2(.-) (110%) generation compared to controls, effects that were either synergistically augmented or suppressed by iron overload, respectively. The in vitro addition of iron (1 micromol/mg protein) to liver cytosolic fractions from euthyroid (97%) and hyperthyroid (173%) rats also enhanced NO generation. The effects of iron overload on mitochondrial O2(.-) production by hyperthyroid rats were reproduced by the in vitro addition of 1 micromol iron/mg protein and abolished by the in vivo pretreatment with the iron chelator desferrioxamine (500 mg/kg). It is concluded that liver oxidative stress induced by iron overload is independent of NO and O2(.-) production in lindane-treated rats, whereas in hyperthyroid animals NO generation is a major factor contributing to this redox imbalance.

Animals↗
PubMed2001

Receptor-mediated endocytosis in an apicomplexan parasite (Toxoplasma gondii).

Endocytosis mechanisms are poorly known in apicomplexan parasites. Here, we show that extracellular tachyzoites of Toxoplasma gondii bind and internalize heparin-like sulfated glycans in a specific, saturable manner. Discrete binding of the glycan occurs at the anterior third of the tachyzoite, where it is rapidly concentrated inside single tubulo vesicular compartments that become multiple with time. The compound is held for several hours intracellularly with no apparent exocytosis or acidification. Incubation in the continuous presence of fluorescein isothiocyanate-conjugated heparin enhances the binding and internalization of this ligand by live tachyzoites. Two tachyzoite surface polypeptides exhibit strong binding and specificity for heparin, making them candidate receptors. Uptake of fluid-phase endocytic tracers occurs via nonspecific pinocytosis in the same region of the parasite cell, but with much lower efficiency. These observations show that extracellular tachyzoites can acquire molecules through both receptor-specific and fluid-phase endocytic mechanisms. Understanding the physiological relevance of these processes for the extracellular and intracellular stages of T. gondii may bring about direct targeting of the parasite by drug delivery into the tachyzoites.

Animals↗
PubMed2001

Evidence for translational selection in codon usage in Echinococcus spp.

We analysed the intragenomic variation in codon usage in Echinococcus spp. by correspondence analysis. This approach detected a trend among genes which was correlated with expression levels. Among the (presumed) highly expressed sequences we found an increased usage of a subset of codons, almost all of them G- or C- ending. Since an increase in these bases at the synonymous sites is against the mutational bias (these genomes are slightly A+-T- rich), we conclude that codon usage in Echinococcus is the result of an equilibrium between compositional pressure and selection, the latter acting at the level of translation, mainly on highly expressed genes. This is the first report where translational selection for codon usage is detected among Platyhelminthes.

Animals↗
PubMed2001

Influence of aging on Kupffer cell respiratory activity in relation to particle phagocytosis and oxidative stress parameters in mouse liver.

The influence of aging on the respiratory activity of stimulated Kupffer cells was investigated in the isolated perfused mouse liver in relation to colloidal carbon phagocytosis, and the content of glutathione (GSH) and protein carbonyls as parameters related to oxidative stress. Livers from aged (22 months) mice exhibited significant 35% and 65% decreases in the carbon uptake and in the carbon-induced O2 consumption compared to young (3 months) animals, respectively, with a concomitant 46% diminution in the carbon-induced O2 consumption/carbon uptake ratio. Hepatic GSH depletion was observed in aged mice compared to young animals, whereas protein oxidation was enhanced. It is concluded that aging leads to an impairment in the functional capacity of Kupffer cells reflected by a substantial reduction in their respiratory burst activity, lessened endocytic capacity and enhanced oxidative stress, that may contribute to increased susceptibility of the liver to noxious challenges.

Aging↗
PubMed2001

[Glucose/insulin response to a glucose overload in subjects at risk for type 2 diabetes].

With the purpose of determining how certain risk factors for type 2 diabetes such as family history of diabetes, obesity and dyslipidemia, affect the glucose-insulin response to a glucose challenge, 135 individuals (77 women and 58) men were studied. Their ages ranged from 20-68 years, their basal glycemic values were less than 110 mg/dL but they were considered at risk for diabetes due to the presence of one or more of those factors. We found that the presence of those risk factors did not affect the glycemic response in any case. However, the basal insulin levels as well as the post-challenge values were increased significantly (p < 0.0001) by the presence of obesity in men as well as in women. Dyslipidemia increased the basal and post challenge glucose insulin values only in men (p < 0.002). The coexistence of obesity and family history of diabetes provoked a decrease in the basal insulin levels as well as in the insulin response to glucose. We conclude that, without alteration of the glycemic response, the presence of risk factors as obesity, dyslipidemia or family history of diabetes leads to basal hyperinsulinemia, as well as glucose stimulated hyperinsulinemia, however the coexistence of obesity and family history of diabetes, is responsible for a deficit in the insulin secretion by the pancreas.

Adult↗
PubMed2000

Comparative analysis of two different subunits of antigen B from Echinococcus granulosus: gene sequences, expression in Escherichia coli and serological evaluation.

Two different Echinococcus granulosus antigen B subunits (AgB8/1 and AgB8/2) were characterized and the structure of the genes encoding these two proteins were compared. DNA sequences were expressed in Escherichia coli and the antigens' diagnostic value was then assessed. The genomic sequence of AgB8/1 has a 92 bp intron in the position corresponding to amino acid 16; the AgB8/2 genomic sequence presents a 68 bp intron in the position corresponding to amino acid 20. Both introns are located between the putative N-terminal hydrophobic sequence and the secreted peptide. A comparison between the AgB8/1 and AgB8/2 nucleotide sequences showed a 53.5% identity among exons and a 50% identity between introns. According to the molecular diversity analysis, the elapsed time since both genes shared a common ancestor would be around 4.2x10(7) years. When the native AgB and the two recombinant antigens (rAgB8/1 and rAgB8/2) were tested in an anti-IgG ELISA, the sensitivity of the native antigen B was 77.41% and its specificity was 81.9%, while rAgB8/1 showed 54.84% of sensitivity and 80.17% of specificity and rAg138/2 had an 83.87% sensitivity and a 98.28% specificity. Statistical analysis confirms that rAgB8/2 has a better performance than rAgB8/1 and native AgB in ELISA.

Amino Acid Sequence↗