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Biomedical subjects

F Fernández

Publications and source records attributed to F Fernández.

At least 19 recordsLinked to original sources
PubMed2003

Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning.

We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n=40) or busulphan (n=28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (P<0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression post-transplant was the development of chronic extensive GVHD (P<0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.

Adult↗
PubMed2003

Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type.

Several lines of evidence support a role for brain-derived neurotrophic factor (BDNF) alterations in the etiology of eating disorders (EDs). BDNF heterozygous knockout mice show alterations in eating behavior, increased body weight and adipocyte hypertrophy. BDNF also regulates the synaptic efficiency through the modulation of key neurotransmitter systems previously known to be involved in ED. These findings, together with the fact that this neurotrophin is expressed in the hypothalamus nuclei associated with weight regulation and feeding control, led us to propose BDNF as a candidate gene for ED. To investigate the possible involvement of this neurotrophin in eating behavior, we screened the BDNF gene in 95 ED patients and identified four sequence variants. Two of them, -374A/T and -256G/A, were found in two patients with anorexia nervosa (AN) and consisted of single-nucleotide mutations within the 5' untranslated region (5'UTR). The other two polymorphisms resulted in a C to T transition located at the 5'UTR of the BDNF gene and an amino-acid substitution within the BDNF precursor protein (Val66Met). We performed a case-control study for these two Single-nucleotide polymorphisms in a sample of 143 ED patients and 112 unrelated controls and found a strong association of restricting AN (ANR) with the Met allele of the Val66Met BDNF polymorphism (2p=0.002). There was also evidence for a significant effect of this sequence variant on the minimum body mass index (MBMI) (2p=0.006). These results suggest that the BDNF Met66 variant may be a susceptibility factor to ED, mainly to ANR and low MBMI.

Adult↗
PubMed2003

Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer.

STUDY OBJECTIVE: To evaluate whether consumption of chlorinated drinking water is associated with bladder cancer. DESIGN: A bibliographic search was conducted and the authors selected studies evaluating individual consumption of chlorinated drinking water and bladder cancer. The authors extracted from each study risk estimates for intermediate and long term (>40 years) consumption of chlorinated water, stratified by sex when possible, and performed meta-analysis for the two exposure levels. A meta-analysis was also performed of the dose-response regression slopes. SETTING: Populations in Europe and North America. PARTICIPANTS: Those included in six case-control studies (6084 incident bladder cancer cases, 10,816 controls) and two cohort studies (124 incident bladder cancer cases) fulfilling the inclusion criteria. MAIN RESULTS: Ever consumption of chlorinated drinking water was associated with an increased risk of bladder cancer in men (combined OR=1.4, 95%CI 1.1 to 1.9) and women (combined OR=1.2, 95%CI 0.7 to 1.8). The combined OR for mid-term exposure in both genders was 1.1 (95% CI 1.0 to 1.2) and for long term exposure was 1.4 (95%CI 1.2 to 1.7). The combined estimate of the slope for a linear increase in risk was 1.13 (95% CI 1.08 to 1.20) for 20 years and 1.27 (95% CI 1.15 to 1.43) for 40 years of exposure in both sexes. CONCLUSIONS: This meta-analysis of the best available epidemiological evidence indicates that long term consumption of chlorinated drinking water is associated with bladder cancer, particularly in men. The observed relative risk is only moderately high, but the population attributable risk could be important as the vast majority of the population of industrialised countries is potentially exposed to chlorination byproducts for long time periods.

Chlorine↗
PubMed2002

ELISA test to detect Chlamydophila pneumoniae IgG.

A new ELISA test (Chlamydophila pneumoniae IgG, Vircell, Spain) to detect Chlamydophila pneumoniae IgG was evaluated. The micro-immunofluorescence (MIF) test was used as reference method. Chlamydia trachomatis and Chlamydophila psittaci elementary bodies were also assayed. Two hundred and sixteen sera were included in the study: 66 from patients with peripheral arterial occlusive disease (Panel 1), 68 from adults with pneumonia (Panel 2), 44 from healthy adults (Panel 3) and 38 from patients with a sexuality transmitted disease by C. trachomatis (Panel 4). In Panel 1, 51 sera (77%) had antibody titres between 32 and 128; 4 out of 15 sera with IgG titres < 32 were positive by ELISA test and 2 sera with 32 IgG titres were uncertain by ELISA; the remaining 60 sera were correctly classified, giving a 91% concordance between the techniques. In Panel 2, 55 sera (81%) had IgG titres between 32 and 512; 2 out of 13 sera with IgG titres < 32 were positive by ELISA and 2 sera with 32 titres were uncertain by ELISA; the remaining 64 sera were correctly classified, giving a 97% concordance. In Panel 3, 22 sera (50%) had IgG titres between 32 and 64; only 1 out of 22 sera with IgG titres < 32 was positive by ELISA, giving a 97% concordance between the techniques. In Panel 4, there were 24 (63%) negative, 10 (26%) uncertain and 4 (10%) positive results by ELISA, giving an 86% concordance. The C. pneumoniae ELISA test demonstrated 100% sensitivity and 85% specificity. The IgG ELISA test demonstrated a good concordance with the MIF test without the drawbacks associated with the latter assay. We conclude that the ELISA test could be an alternative to the MIF test.

Antibodies, Bacterial↗
PubMed2002

Nutritional regulation of glucose-6-phosphatase gene expression in liver of the gilthead sea bream (Sparus aurata).

To examine the role of glucose-6-phosphatase (G6Pase) in glucose homeostasis in the diabetes-like experimental model of carnivorous fish, we analysed postprandial variations and the effect of starvation, ration size and diet composition on the regulation of G6Pase expression at the enzyme activity and mRNA level in the liver of gilthead sea bream (Sparus aurata). G6Pase expression increased in long-term starved or energy-restricted fish. In contrast to data reported for other fish species, short-term regulation of G6Pase expression was found in regularly fed S. aurata. G6Pase mRNA levels were lowest between 4 and 15 h after food intake, whereas minimal enzyme activity was observed 10-15 h postprandially. Alterations of plasma glucose levels affect G6Pase in mammals. However, the carbohydrate content of the diet did not affect hepatic expression of G6Pase in S. aurata, suggesting that a different molecular mechanism is involved in the control of G6Pase expression in fish. Although G6Pase was unaffected, high-carbohydrate low-protein diets increased glucokinase (GK) expression and thus allowed a metabolic adaptation favouring glycolysis over gluconeogenesis. Interestingly, only the nutritional conditions that promoted variations in the blood glucose levels resulted in changes in the hepatic expression of G6Pase. These findings indicate a concerted regulation of G6Pase and GK expression and suggest that the direction and rate of the glucose-glucose-6-phosphate substrate cycle flux is finely regulated in the liver of S. aurata, challenging the role attributed to deficient regulation of G6Pase or GK expression in the low ability of carnivorous fish to metabolize glucose.

Animals↗
PubMed2002

Effect of soil parameters on radon entry into a building by means of the transrad numerical model.

High indoor radon concentration means an increased risk of developing lung cancer. When high radon levels are present in a dwelling, the major source is normally the soil. Therefore, it is useful to know the radon concentration field in the soil underneath a building. A steady-state two-dimensional radon transport model has been used to calculate the effect of a reference building on the soil radon concentration, and the influence of soil parameters on radon entry through a single crack in the basement. Both advective and diffusive flows are considered. Away from the building, the well-known undisturbed soil radon concentration profile has been obtained, while under the house the radon level is increased. A variability analysis around the reference site has shown that the most relevant soil parameters on the radon flux at the top of the crack are, in this case, effective diffusion coefficient, soil gas-permeability and deep soil radon concentration.

Air Pollutants, Radioactive↗
PubMed2001

Modulated release of cyclosporine from soluble vinyl pyrrolidone--hydroxyethyl methacrylate copolymer hydrogels. A correlation of 'in vitro' and 'in vivo' experiments.

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer compositions f(VP)=0.52 (namely VP--HEMA 60--40) and 0.42 (VP--HEMA 40--60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates the in vitro release of the drug (with time profiles from a few days to several weeks for the VP--HEMA 60--40 and 40--60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP--HEMA 40--60) reverts the immune response more slowly (2--4 weeks) compared to the more hydrophilic one (VP--HEMA 60--40, 1--2 weeks).

Animals↗
PubMed2001

LUMO energy of model compounds of bispyridinium compounds as an index for the inhibition of choline kinase.

Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene-1,4-diylmethylene)]bis(4-pyridinium) dibromides bearing various groups at C-4 of the pyridinium moiety were synthesized and examined for their inhibition of choline kinase (ChoK) and antiproliferative activities. The C-4 substituents include electron-releasing, neutral or electron-withdrawing groups. A one-parameter regression equation has been derived which satisfactorily describes the ex vivo inhibitory potency of ChoK of the title compounds. The electronic effect plays a critical function in the ex vivo inhibition of ChoK although the role of electrostatic interactions could be altered due to a solvation process of both ChoK and ligands.

Choline Kinase↗
PubMed2001

First isolation of rotavirus associated with neonatal diarrhoea in guanacos (Lama guanicoe) in the Argentinean Patagonia region.

Group A rotavirus (RV) and coronavirus (CV) are common viral pathogens associated with neonatal diarrhoea in numerous animal species. The purpose of this work was to investigate the presence of these viral agents in two farm populations of captured guanacos (Lama guanicoe) in the Argentinean Patagonia region, that developed severe diarrhoea outbreaks. Stool and serum samples were analysed for RV and bovine CV antigen and antibody enzyme-linked immunosorbent assay. Rotavirus was detected in faeces from two new-born guanacos with acute diarrhoea, one in each farm. After electrophoretic analysis, each isolated strain, showed a distinctive long dsRNA electropherotype characteristic of group A rotaviruses (4:2:3:2). In addition, 95% (38 of 40) of the sampled animals were positive for RV antibodies, suggesting a high prevalence of RV infection in the populations tested. No evidence of CV circulation by antigen or antibody analysis was observed. To our knowledge, this is the first report of the detection and isolation of RV associated with neonatal diarrhoea in Lama guanicoe.

Animals↗
PubMed2001

MIB1 proliferation index in breast infiltrating carcinoma: comparison with other proliferative markers and association with new biological prognostic factors.

AIMS: In breast invasive carcinoma our objectives were I) to compare cellular proliferation determined by MIB1 index with S-phase fraction (SPF) assessed by flow cytometry and with mitotic index, and II) to examine the association of MIB1 index with classical and with new biological prognostic factors [bcl-2, p53, c-erbB-2 and cathepsin D (CD)]. METHODS AND RESULTS: From 102 cases of breast invasive carcinoma, 5-microm thick serial sections were cut from formalin-fixed, paraffin-embedded tissue blocks, and processed for detection of CD, c-erbB-2, p53, bcl-2, Ki-67 antigen MIB-1 and estrogen receptors (ER) and progesterone receptors (PR). SPF was measured by flow cytometry in fresh-frozen tissue samples taken from the carcinoma in each patient. MIB1 index was correlated with SPF (rho=0.45, p<0.0001) and with mitotic index (rho=0.42, p<0.0001). The MIB-1 index was positively associated with the histological grade (p=0.001), tumor size (p=0.04) and the presence of metastases in axillary lymph nodes (p=0.01). MIB1 was associated directly with p53 (p=0.045) and inversely with bcl-2 (p=0.0002). The MIB-1 index was not statistically associated with c-erbB-2. There was a weak association between MIBI index and stromal cell CD. The median MIB1 index was higher in tumors with moderate to strong CD staining of stromal cell, but the difference did not reach statistical significance (p=0.09). CONCLUSIONS: MIB1 index correlates with well established methods for assessing tumor proliferation and with parameters of an aggressive phenotype of tumor. MIB1 index is an effective and readily accessible method for assessing tumor proliferation in breast carcinoma.

Adult↗
PubMed2000

Glucokinase gene expression is nutritionally regulated in liver of gilthead sea bream (Sparus aurata).

Glucose intolerance in carnivorous fish has been attributed to the lack of hepatic glucokinase (GK) activity. Transcription/translation assay and transient transfection of COS-7 cells with a cDNA encoding Sparus aurata liver GK showed the functionality of the enzyme in vitro. The endogenous fish hepatic GK had lower affinity for glucose than the rat enzyme. The GK activity values in fed fish were similar to those reported for starved and diabetic rats. In this study, we also addressed the nutritional regulation of GK gene expression in fish liver. Starvation and energy restriction decreased S. aurata hepatic GK mRNA and activity levels, as previously reported in rats. In contrast, the fish enzyme expression exhibited a delayed onset during the daily feeding rhythm. These findings demonstrate for the first time the presence and the nutritional modulation of a functional GK activity in fish liver and contribute to explain the low ability of carnivorous fish to metabolize carbohydrates.

Acetylglucosamine↗
PubMed2000

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression is regulated by diet composition and ration size in liver of gilthead sea bream, Sparus aurata.

Modulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF-2-K/Fru-2,6-P(2)ase) gene expression by diet composition and ration size was studied in the liver of gilthead sea bream, Sparus aurata. From five different types of diet supplied to fish, those with either high carbohydrate/low protein or high carbohydrate/low lipid content stimulated 6PF-2-K/Fru-2,6-P(2)ase expression at the levels of mRNA, immunodetectable protein and kinase activity as well as promoting higher fructose-2,6-bisphosphate (Fru-2,6-P(2)) values. The expression of the bifunctional enzyme and Fru-2,6-P(2) levels showed also direct dependence on the quantity of diet supplied. These findings demonstrate for the first time nutritional regulation of 6PF-2-K/Fru-2,6-P(2)ase at mRNA level by diet composition and ration size and suggest that the carnivorous fish S. aurata can adapt its metabolism, by stimulation of liver glycolysis, to partial substitution of protein by carbohydrate in the diet. In addition, the expression of 6PF-2-K/Fru-2,6-P(2)ase can be used as an indicator of nutritional condition.

Animals↗
PubMed2000

Fungemia with Saccharomyces cerevisiae in two newborns, only one of whom had been treated with ultra-levura.

Ultra-Levura (Upsamedica, Spain) is a yeast (Saccharomyces boulardii) widely used as a biotherapeutic agent. To date, few adverse effects have been reported, although fungemia with Saccharomyces cerevisiae can occur in weak and immunosuppressed patients. Reported here are two cases of fungemia with Saccharomyces cerevisiae. One patient had been treated with Ultra-Levura and the other contracted the infection from the first. This is the first report of infection with Saccharomyces boulardii (Saccharomyces cerevisiae) in a patient who was not being treated with the agent.

Female↗
PubMed2000

Controlled release of cyclosporine from VP-HEMA copolymer systems of adjustable resorption monitorized by MEKC.

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of drugs, taking cyclosporine as a model system. The copolymerization parameters described as reactivity ratios, rVP = 0.08 and rHEMA = 7.97, indicate that the copolymer systems prepared at high conversion have two main components with a microstructural arrangement which depends on the average composition, i.e., an initial HEMA-rich copolymer and a final PVP homopolymer or VP-rich copolymer. This microstructural distribution controls the resorption rate of the polymeric support and therefore the release process of cyclosporine which is demonstrated experimentally by the application of a modern technique known as micellar electrokinetic capillary chromatography (MEKC).

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2000

Patients with mantle-cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation.

Two patients with disseminated mantle-cell lymphoma relapsed 24 and 13 months, respectively, after high-dose chemotherapy and autologous stem cell transplantation (autoSCT). Both patients had an HLA-identical sibling and received an allogeneic stem cell transplant (alloSCT) 32 and 18 months after autologous transplant, after conditioning with fractionated 12 Gy total body irradiation plus cyclophosphamide 120 mg/kg. They are both alive and in complete remission 24 months after transplant. Both patients have developed chronic graft-versus-host disease and their Karnofsky performance status is 90%. AlloSCT may offer a useful approach in a subgroup of patients with mantle-cell lymphoma who have relapsed after autologous transplantation.

Antineoplastic Combined Chemotherapy Protocols↗