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Biomedical subjects

J M García

Publications and source records attributed to J M García.

At least 19 recordsLinked to original sources
PubMed2007

Evaluation of the viability of cultured corneal endothelial cells by quantitative electron probe X-ray microanalysis.

Construction of artificial organs and tissues by tissue engineering is strongly dependent on the availability of viable cells. For that reason, the viability and the physiological status of cells kept in culture must be evaluated before the cells can be used for clinical purposes. In this work, we determined the viability of isolated rabbit corneal endothelial cells by trypan blue staining and quantitative electron probe X-ray microanalysis. Our results showed that the ionic content of potassium in cultured corneal endothelial cells tended to rise initially, but significantly decreased in cells in the fifth (and final) subculture, especially in comparison to cells in the fourth subculture (P < 0.001). However, the concentration of sulfur was higher in the fifth subculture than in the fourth subculture (P < 0.001), with a nonsignificant increase in sodium in the fifth subculture (P = 0.031). These data imply a remarkable decrease in the K/Na ratio from the fourth to the fifth subculture. Our microanalytical results, along with the morphological differences between cells in the last two subcultures, are compatible with an early phase of the preapoptotic process in the fifth subculture, and suggest that cells of the first four subcultures would be better candidates for tissue engineering.

Animals↗
PubMed2006

Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer.

Colorectal cancer is a major cause of cancer death worldwide. A number of key oncogenes and tumor suppressor genes have been proposed to drive progression from healthy colonic epithelia to malignant tumors, including members of the Wnt/beta-catenin pathway. Recently, CpG island promoter hypermethylation was shown to cause inactivation of two extracellular Wnt inhibitors in colon cancer: secreted frizzled-related proteins (sFRPs) and Wnt inhibitory factor-1 (WIF-1). Here, we show for the first time that another extracellular Wnt inhibitor, the DICKKOPF-1 (DKK-1) gene, is transcriptionally silenced by CpG island promoter hypermethylation in colon cancer cell lines (n=9), whereas treatment with the DNA-demethylating agent 5-aza-2-deoxycytidine restored DKK-1 expression. Restoration of DKK-1 function in non-expressing cells bearing a truncated APC (Adenomatous Polyposis Coli) gene had no effect on beta-catenin/T-cell factor-dependent transcription, but induced tumor suppressor-like features such as reduced colony formation density and tumor growth inhibition in nude mice. These results suggest additional functions for DKK-1 other than inhibiting canonical Wnt signaling. In primary colorectal tumors, DKK-1 was found hypermethylated in 17% (nine of 54) of cases. Furthermore, while for both SFRP-1 and WIF-1 methylation-associated silencing occurred across the whole spectrum of colorectal tumorigenesis, DKK-1 promoter was selectively hypermethylated in advanced colorectal neoplasms (Duke's C and D tumors).

Adaptor Proteins, Signal Transducing↗
PubMed2006

The presence of an intronic deletion in p73 and high levels of ZEB1 alter the TAp73/DeltaTAp73 ratio in colorectal carcinomas.

TAp73 variants largely mimic p53 suppressor activities, while DeltaTAp73 forms act as oncogenes through the inactivation of p53 and TAp73. The present study analysed how TAp73 and DeltaTAp73 levels might be affected by the presence of a 73 bp deletion in a regulatory region of p73. The clinical relevance of this deletion was also examined. ZEB1 can bind to the region repressing p73 transcription in vitro. The relationship between ZEB1 and p73 variant expression levels was studied in the context of this deletion and the levels of the ZEB1 cofactors p300 and CtBP. Tumour and normal tissue from 81 colorectal cancer patients was analysed to evaluate firstly the levels of TAp73, DeltaTAp73 (DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73), ZEB1, p300, and CtBP by quantitative real-time RT-PCR, and secondly the presence of the 73 bp deletion. Tumour characteristics were examined in each patient. Suppressor and oncogenic isoforms of p73 were co-up-regulated in tumour tissues. Overexpression of p73 variants was associated with adverse tumour features. The 73 bp deletion was present in 40% of the patients and was associated with adverse pathological parameters of the tumours and also with TAp73 down-regulation. In those cases harbouring the deletion, the levels of ZEB1 and those of DeltaEx2p73, DeltaEx2/3p73, and DeltaNp73 correlated directly. Variations in the concentration of p300 affected the observed correlations between ZEB1 and the different p73 variants. In conclusion, in colorectal cancer, the 73 bp deletion in the first intron of the p73 gene and different expression levels of ZEB1 and p300 may act in concert to affect the ratio of TAp73/DeltaTAp73 forms, favouring p73 oncogenic variants. In addition, up-regulation of p73 oncogenic isoforms predicts a poor prognosis based on its relationship with advanced tumour stage.

Aged↗
PubMed2006

Blast2GO goes grid: developing a grid-enabled prototype for functional genomics analysis.

The vast amount in complexity of data generated in Genomic Research implies that new dedicated and powerful computational tools need to be developed to meet their analysis requirements. Blast2GO (B2G) is a bioinformatics tool for Gene Ontology-based DNA or protein sequence annotation and function-based data mining. The application has been developed with the aim of affering an easy-to-use tool for functional genomics research. Typical B2G users are middle size genomics labs carrying out sequencing, ETS and microarray projects, handling datasets up to several thousand sequences. In the current version of B2G. The power and analytical potential of both annotation and function data-mining is somehow restricted to the computational power behind each particular installation. In order to be able to offer the possibility of an enhanced computational capacity within this bioinformatics application, a Grid component is being developed. A prototype has been conceived for the particular problem of speeding up the Blast searches to obtain fast results for large datasets. Many efforts have been done in the literature concerning the speeding up of Blast searches, but few of them deal with the use of large heterogeneous production Grid Infrastructures. These are the infrastructures that could reach the largest number of resources and the best load balancing for data access. The Grid Service under development will analyse requests based on the number of sequences, splitting them accordingly to the available resources. Lower-level computation will be performed through MPIBLAST. The software architecture is based on the WSRF standard.

Computational Biology↗
PubMed2005

A potentiostatic study of oxygen transport through poly(2-ethoxyethyl methacrylate-co-2,3-dihydroxypropylmethacrylate) hydrogel membranes.

The oxygen permeability and diffusion coefficients of hydrogel membranes prepared with copolymers of 2-ethoxyethyl methacrylate (EEMA)/2,3-dihydroxypropylmethacrylate (MAG) with mole fraction of the second monomer in the range between 0 and 0.75 are described. Values of the permeability and diffusion coefficients of oxygen are determined by using electrochemical procedures involving the measurement of the steady-state current in membranes prepared by radical polymerization of the monomers. The results obtained for the transport properties were analyzed taking into account the fractional free volumes, the cohesive energy densities and the glass transition temperatures of the hydrogels.

Biocompatible Materials↗
PubMed2004

Finite element study of intramedullary osteosynthesis in the treatment of trochanteric fractures of the hip: Gamma and PFN.

The ongoing debate surrounding the surgical treatment of trochanteric hip fractures, particularly unstable fractures, has led to continuous changes in the design of well-established implants and to the development of new ones. The goal of this paper was to use a finite element simulation to compare the biomechanical behaviour of two intramedullary implants most often used at the University Hospital of Zaragoza: the standard Gamma nail (Howmedica) and the proximal femoral nail (PFN, Stratec). The main focus was on the displacements of the fracture focus and the stress distributions along the femur and the implant. Both nails produced an important redistribution of stress in the bone tissue, but the redistribution of peak stress was higher for the Gamma nail. On the other hand, with PFN there were smaller displacements at the fracture site. Finally, under the same workload, the Gamma nail supported higher stresses than the PFN.

Aged↗
PubMed2004

Dentine structure and mineralization in hypocalcified amelogenesis imperfecta: a quantitative X-ray histochemical study.

OBJECTIVE: This study was undertaken in order to establish the structural and mineralization pattern of the response of dentine to alterations in enamel in hypocalcified amelogenesis imperfecta (AI). DESIGN: The images and data obtained with scanning electron microscopy and electron probe X-ray microanalysis in enamel and dentine specimens from control and affected teeth were compared in this study. PATIENTS AND METHODS: We compared 46 fragments of permanent teeth from patients with clinically diagnosed hypocalcified AI and 20 normal permanent teeth. All specimens were prepared for electron probe X-ray microanalysis. RESULTS: Dentine is characterized by thickening of the peritubular dentine and partial obliteration of the dentinal tubules that does not give rise to a compact sclerotic cast. In dentine, calcium levels were significantly higher in teeth with clinically hypocalcified AI in relation with control teeth (P < 0.001). CONCLUSIONS: Dentine is affected in hypocalcified AI increasing mineralization (narrower tubules and higher content of calcium) in response to enamel disorder.

Adolescent↗
PubMed2003

[Simulation through the method of finite element of alendronate in a model of bone remodeling based on damage mechanics].

Mechanical loads are one of the main factors that affect bone remodelling process. This phenomenon is widely applied to the study of prosthetic replacement, for example hip prosthesis. Elderly people are the most common patient to receive a hip replacement surgery. Alendronate is a drug that is being used to increase bone mineral content in patients with poor bone quality. This work uses a mechanical model based on damage mechanics, which considers bone's porosity as the damage variable, a mechanical stimulus associated thermodynamically to this variable, a damage criterion and an evolution damage law. Our approach simulates the degree of mineralization changes as well as the decrease of BMU activation frequency due to Alendronate doses. The biological changes generated by the drug directly affect the damage's evolution law. As a first approach the two biological parameters to be modeled are the surface of remodelling as well as the degree of mineralization (ash fraction) of the bone. Results show a good correlation with experimental data from alendronate's treatments for short term simulations (1-2 years).

Alendronate↗
PubMed2002

Anisotropic bone remodelling model based on a continuum damage-repair theory.

The purpose of this paper is to present and discuss a new model for internal bone remodelling. We state that the evolution of the internal variables of the bone microstructure and its incidence on the modification of the elastic constitutive parameters may be formulated following the exact principles of Continuum Damage Mechanics (CDM), although no actual damage is considered. A remodelling tensor, analogous to the standard damage tensor, is proposed which completely characterises the state of the homogenised bone microstructure and, therefore, its stiffness. This tensor is defined in terms of the apparent density and the "fabric tensor" associated with porosity and directionality of the trabeculae, respectively. Contrary to standard damage mechanics, its variation may be negative to allow for material "repair". The different elements that compose the theory are then established, such as the mechanical stimulus which, as is common in CDM, was chosen as the tensor that is thermodynamically associated to the remodelling one. The resorption and apposition criteria (similar to the damage criterion) were also expressed in terms of this mechanical stimulus and, finally, the evolution law, to define the change rate of the remodelling tensor. An associated flow rule is proposed that fulfils a principle of minimum mechanical dissipation for convex remodelling criteria (the case in question here). Some other important experimental features are deduced naturally from the model, such as the coincidence of the principal directions of the fabric tensor with those of the elasticity tensor, or the fact that the principal directions of the fabric tensor tend to align with the principal directions of stress. This model is applied to the study of the remodelling evolution of the proximal extremity of the femur, obtaining results very similar to experimental data.

Anisotropy↗
PubMed2002

Multimedia telehomecare system using standard TV set.

Nowadays, there are a very large number of patients that need specific health support at home. The deployment of broadband communication networks is making feasible the provision of home care services with a proper quality of service. This paper presents a telehomecare multimedia platform that runs over integrated services digital network and internet protocol using videoconferencing standards H.320 and H.323, and standard TV set for patient interaction. This platform allows online remote monitoring: ECG, heart sound, blood pressure. Usability, affordability, and interoperability were considered for the design and development of its hardware and software components. A first evaluation of technical and usability aspects were carried forward with 52 patients of a private clinic and 10 students in the University. Results show a high rate (mean = 4.33, standard deviation--SD = 1.63 in a five-points Likert scale) in the global perception of users on the quality of images, voice, and feeling of virtual presence.

Computer Communication Networks↗
PubMed2001

Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer.

The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.

Breast Neoplasms↗
PubMed2001

Glancing-angle diffraction anomalous fine structure of InAs quantum dots and quantum wires.

We have performed Diffraction Anomalous Fine Structure measurements at the As K-edge of self-growth InAs/InP(001) Quantum Wires and InAs/GaAs(001) Quantum Dots. The samples have been grown by Molecular Beam Epitaxy and their equivalent thickness is of 2.5 monolayers. We have measured the (440) and (420) Bragg reflections in glancing-angle scattering geometry, at incidence angles close to the substrate critical angle. We demonstrate the feasibility of the experiment reporting, for the first time. Diffraction Anomalous Fine Structure spectra of such low coverage epitaxial layers, and we show that the analysis of the Diffraction Anomalous Fine Structure lineshape together with the analysis of oscillatory part of the signal, can provide information about composition and strain of the nanostructures.

Journal Article↗
PubMed2001

Different expression of P14ARF defines two groups of breast carcinomas in terms of TP73 expression and TP53 mutational status.

In 95 breast carcinomas, we investigated P14ARF and TP73 mRNA expression and their relationship to TP53 mutations, determined by an immunohistochemical method, studying several clinicopathologic features of the tumors. P14ARF and TP73 mRNA levels were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR), using beta-actin as a control. P14ARF was overexpressed in 19% of the cases and underexpressed in 24%. TP73 was overexpressed in 22% of the tumors, and normal levels were found in the remaining 78%. The analysis of TP53 showed positive immunostaining in 38% of cases. The association of P14ARF and TP73 overexpression was statistically significant, as was the association between positive TP53 staining and TP73 overexpression. P14ARF was related to TP53 only in those cases in which there was low expression of P14ARF. Concomitant overexpression of P14ARF and TP73 was statistically related to positive TP53 immunostaining. The analysis of concomitant P14ARF and TP73 overexpression and clinicopathologic parameters of the tumors showed a statistically significant difference with respect to peritumoral vessel invasion (P = 0.01), lymph node metastasis (P = 0.03), negative ERBB2 expression (P = 0.005), and more advanced pathologic stages (P = 0.03). These results suggest that overexpression of P14ARF and TP73 could be implicated in breast carcinoma tumorigenesis and, ultimately, in the phenotypic features of these lesions.

Adenocarcinoma↗
PubMed2001

Application of an anisotropic bone-remodelling model based on a damage-repair theory to the analysis of the proximal femur before and after total hip replacement.

In this work, a new model for internal anisotropic bone remodelling is applied to the study of the remodelling behaviour of the proximal femur before and after total hip replacement (THR). This model considers bone remodelling under the scope of a general damage-repair theory following the principles of continuum damage mechanics. A "damage-repair" tensor is defined in terms of the apparent density and Cowin's "fabric tensor", respectively, associated with porosity and directionality of the trabeculae. The different elements of a thermodynamically consistent damage theory are established, including resorption and apposition criteria, evolution law and rate of remodelling. All of these elements were introduced and discussed in detail in a previous paper (García, J. M., Martinez, M. A., Doblaré, M., 2001. An anisotrophic internal-external bone adaptation model based on a combination of CAO and continuum damage mechanics technologies. Computer Methods in Biomechanics and Biomedical Engineering 4(4), 355-378.), including the definition of the proposed mechanical stimulus and the qualitative properties of the model. In this paper, the fundamentals of the proposed model are briefly reviewed and the computational aspects of its implementation are discussed. This model is then applied to the analysis of the remodelling behaviour of the intact femur obtaining densities and mass principal values and directions very close to the experimental data. The second application involved the proximal femoral extremity after THR and the inclusion of an Exeter prosthesis. As a result of the simulation process, some well-known features previously detected in medical clinics were recovered, such as the stress yielding effect in the proximal part of the implant or the enlargement of the cortical layer at the distal part of the implant. With respect to the anisotropic properties, bone microstructure and local stiffness are known to tend to align with the stress principal directions. This experimental fact is mathematically proved in the framework of this remodelling model and clearly shown in the results corresponding to the intact femur. After THR the degree of anisotropy decreases tending, specifically in the proximal femur, to a more isotropic behaviour.

Anisotropy↗
PubMed2001

[Pulmonary nocardiosis as a cause of radiographic imaging of multiple pulmonary nodules].

Lung nocardiosis is a rare disease affecting patients with lymphoreticular neoplasm, immunodeficiency or chronic obstructive pulmonary disease; it can also affect patients who have received transplants. We report a case of lung nocardiosis in which radiographic presentation was acute, with a pattern of multiple bilateral pulmonary nodules ("cannonballs"), requiring us to rule out metastatic disease to arrive at a diagnosis. The patient responded slowly to antibiotic treatment until full resolution.

Aged↗
PubMed2001

Reduction of oil bitterness by heating of olive (Olea europaea) fruits.

Olives (Olea europaea) of the Manzanilla and Verdial varieties, harvested at the green mature stage of ripening, were heated at 30, 40, 45, and 50 degrees C during 24 h and at 40 degrees C during 24, 48, and 72 h, respectively. Just after treatments, oils were physically extracted from the olives. Olive heating promotes a reduction of oil bitterness in direct relationship to the time and temperature used. Fruit heating at < or =40 degrees C during 24 h did not produce significant changes of acidity, UV absorption, peroxide index, panel test score, or oxidative stability of the obtained oils. Both longer treatments at 40 degrees C and heating at >40 degrees C yielded oils with less oxidative stability. Oils obtained from olives heated at > or =40 degrees C showed higher concentrations of chlorophylls and carotenes. For each olive variety, a good correlation between oil bitterness and content of hydroxytyrosol secoiridoid derivatives was found.

Food Handling↗