Maria J. Pascual

Involvement of Fcγ receptor IIIA genotypes in susceptibility to rheumatoid arthritis

OBJECTIVE To investigate a possible association of Fcgamma receptor IIIA (FcgammaRIIIA) gene polymorphism at position 158 with susceptibility to, and the outcome of, rheumatoid arthritis (RA). METHODS One hundred seventeen RA patients and 142 unrelated healthy control subjects from the same geographic area were studied. Genotyping for FcgammaRIIIA-158V/F was performed by a method based on polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis using amplification-created restriction sites. HLA-DRB1 typing by PCR-sequence-specific oligonucleotide hybridization (reverse hybridization) was also performed. RESULTS Allele and genotype distributions in healthy controls were similar to those reported in other populations. The overall distribution of genotypes in the patients was significantly different from that in the controls (P = 0.023, by chi-square test from 3 x 2 contingency table). An overrepresentation of the FcgammaRIIIA-158FF genotype in the patients was observed (for 158FF versus non-158FF P = 0.01, odds ratio [OR] 1.98, 95% confidence interval [95% CI] 1.16-3.4). However, the FcgammaRIIIA-158VF genotype was increased in controls (for 158VF versus non-158VF P = 0.021, OR 0.54, 95% CI 0.32-0.92). No associations were found with any of a series of clinical parameters. Analysis of FcgammaRIIIA-158FF along with shared epitope showed that the presence of both factors increased the susceptibility to RA (P = 0.0009, OR 3.6, 95% CI 1.63-8.01); however, they probably do not interact to produce this effect. CONCLUSION These results indicate that the FcgammaRIIIA-158 genotypes confer differential susceptibility to RA in our study population. Further studies to elucidate the role of this polymorphism in the pathogenesis of RA and other autoimmune diseases are warranted.

IL-6 promoter polymorphisms in rheumatoid arthritis.

We investigated the possible association between the IL-6 promoter polymorphisms, at positions −622 and −174, and susceptiblity to, and/or outcome of, rheumatoid arthritis (RA). A total of 163 patients with RA and 157 healthy controls were genotyped for IL-6 using a PCR-RFLP method. The −622 and −174 alleles were in complete linkage disequilibrium. No difference was observed in the distribution of IL-6 promoter genotype or allele frequencies between RA patients and controls. However, a significant difference in the mean age at disease onset between IL-6 genotypes was observed. The present data appear to rule out an important role of IL-6 promoter polymorphisms in the susceptibility to RA. However, IL-6 genotypes may contribute to the pathogenesis of the disease by influencing the age at disease onset.

Nanocrystallisation in oxyfluoride systems: mechanisms of crystallisation and photonic properties

Abstract Rare earth (RE) doped oxyfluoride glass ceramics possess interesting optical properties with applications in telecommunications and optoelectronics, such as solid state lasers, optical amplifiers, etc. These materials combine the transparency and mechanical and chemical resistance of aluminosilicate glasses with the low phonon energy and facile incorporation of RE ions in the fluoride crystals. The incorporation of RE ions in the crystalline phases enhances the laser emission intensity, a major property of these materials. Transparency is achieved when crystal size is in the nanometric scale, usually below 40 nm, which avoids light scattering. A strict control of the nucleation and crystal growth processes is therefore necessary which requires a deep knowledge of the crystallisation mechanisms. The great activity and publications in this field in the last decades merit a review providing a comparative study of the different nanoglass ceramic systems, their structural and optical characterisation and their main properties and applications. This is the objective of this review paper which includes 227 references. A general discussion on glass nucleation and crystallisation theories and more relevant crystallisation parameters and characterisation techniques are put forward in the first section of the review, focused on nanocrystallisation processes in oxyfluoride systems. In the second section, the principal RE doped glass ceramics are presented. After a general introduction about the luminescence processes, including up- and down-conversion, the behaviour of RE elements in glasses and crystals are discussed. Glass ceramic compositions have been divided as follows: glass ceramics with a glass composition following Wang and Ohwaki’s oxyfluoride glass ceramic, and glass ceramics with different matrix compositions, arranged by crystalline phases. Relevant properties, mainly optical and laser, are described in each system along with the most relevant applications of these materials.

The telomeric part of the HLA region predisposes to rheumatoid arthritis independently of the class II loci

We have evaluated the possible contribution of genes besides DQ and DR to the association of HLA with rheumatoid arthritis (RA). To this end, we have looked at the allele distributions of six microsatellites, D6S1014, D6S2673, TNFalpha, MIB, C1-2-5, and C1-3-2 among 132 RA patients and 254 controls. We have defined 19 microsatellite clusters corresponding to previously described ancestral haplotypes. One of them was D6S1014*143-D6S273*139-TNFalpha*99-MIB*350-C1-2-5*196-C1-3-2*354, often found associated with DQB1*0201-DRB1*0301. As part of this microsatellite cluster, the allele MIB*350 was found to be a RA-predisposing factor, independent of DRB1*0301 and RA-predisposing haplotypes DQB1*03-DRB1*04 and DQB1*0501-DRB1*01. We conclude that the telomeric part of the HLA region contains a locus conferring predisposition to RA independently of HLA class II.

Laser cladding of bioactive glass coatings

Laser cladding by powder injection has been used to produce bioactive glass coatings on titanium alloy (Ti6Al4V) substrates. Bioactive glass compositions alternative to 45S5 Bioglass were demonstrated to exhibit a gradual wetting angle-temperature evolution and therefore a more homogeneous deposition of the coating over the substrate was achieved. Among the different compositions studied, the S520 bioactive glass showed smoother wetting angle-temperature behavior and was successfully used as precursor material to produce bioactive coatings. Coatings processed using a Nd:YAG laser presented calcium silicate crystallization at the surface, with a uniform composition along the coating cross-section, and no significant dilution of the titanium alloy was observed. These coatings maintain similar bioactivity to that of the precursor material as demonstrated by immersion in simulated body fluid.

Alkali-free bioactive glasses for bone tissue engineering: a preliminary investigation.

An alkali-free series of bioactive glasses has been designed and developed in the glass system CaO-MgO-SiO(2)-P(2)O(5)-CaF(2) along the diopside (CaMgSi(2)O(6))-fluorapatite (Ca(5)(PO(4))(3)F)-tricalcium phosphate (3CaO·P(2)O(5)) join. The silicate network in all the investigated glasses is predominantly coordinated in Q(2) (Si) units, while phosphorus tends to remain in an orthophosphate (Q(0)) environment. The in vitro bioactivity analysis of glasses has been made by immersion of glass powders in simulated body fluid (SBF) while chemical degradation has been studied in Tris-HCl in accordance with ISO-10993-14. Some of the investigated glasses exhibit hydroxyapatite formation on their surface within 1-12 h of their immersion in SBF solution. The sintering and crystallization kinetics of glasses has been investigated by differential thermal analysis and hot-stage microscopy, respectively while the crystalline phase evolution in resultant glass-ceramics has been studied in the temperature range of 800-900°C using powder X-ray diffraction and scanning electron microscopy. The alkaline phosphatase activity and osteogenic differentiation for glasses have been studied in vitro on sintered glass powder compacts using rat bone marrow mesenchymal stem cells. The as-designed glasses are ideal candidates for their potential applications in bone tissue engineering in the form of bioactive glasses as well as glass/glass-ceramic scaffolds.

Genetic polymorphisms in Spanish rheumatoid arthritis patients: an association and linkage study

HLA polymorphism accounts only for approximately one-third of the genetic predisposition to rheumatoid arthritis (RA). To investigate the role of other loci in the susceptibility to RA, we have performed an analysis of several polymorphisms in genes of immune-related function: IL-10 −1082, −819, −592 promoter single nucleotide polymorphisms (SNPs), IL-10G and IL-10R microsatellites, IL-6 −622 promoter SNP, FcγRIIIA Val/Phe-158 polymorphism, IL-1 receptor antagonist VNTR, and the IKBL+738 T/C mutation. The analysis has been performed on a case–control study and also on RA trios. IL-10G12 was found to be associated with RA in the case–control study (18% in RA patients vs 9% in controls: P=0.001; pc<0.05). This allele was also more often transmitted than not transmitted (10 vs 5). No other allele in the present study is found to be associated to RA. Our data suggest that most of the loci studied play no major role in the susceptibility to RA, the IL-10 gene being the sole exception.

Rheumatoid arthritis in southern Spain: toward elucidation of a unifying role of the HLA class II region in disease predisposition.

OBJECTIVE To evaluate the contributions of HLA-DQ and -DR polymorphisms to susceptibility to rheumatoid arthritis (RA) in a population in southern Spain, and to compare the value of the shared epitope (SE) and RA protection (RAP) models in accounting for the HLA class II regions contribution to RA predisposition. METHODS One hundred sixty RA patients and 153 healthy controls were typed for HLA-DRB1 and -DQB1 using high-resolution DNA techniques. Distributions of predisposing DRB1 alleles in patients and control subjects according to the SE model were compared with distributions of predisposing DQ and protective DERAA-positive DRBI alleles according to the RAP model. RESULTS DQ3 (DQBI*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles predisposed individuals to RA independently of SE-positive DRB1 alleles. DQ3/3-homozygous individuals had the strongest risk of developing RA. DQ3 molecules predisposed to RA more than did DQ5 molecules. The weaker predisposition mediated by DQ5 included the DRB1*1001-carrying haplotype; no DRB1*1001-homozygous patients were observed. DRBI*0401 played a unique role in the contribution of DQ3-DR4 haplotypes to RA, in spite of its low frequency in southern Spain. CONCLUSION The low prevalences of RA and of mild disease observed in Spain, and in southern Europe in general, can be explained in great part by the low frequency of DQ3-DR4 haplotypes, especially those carrying DRB1*0401. However, the overall distribution of HLA-DQ and -DR alleles in RA patients compared with control subjects is similar to that in other European and North American populations. A model involving both DQ and DR can best account for the contribution of HLA to RA.

Sintering process of glasses in the system Na2O–B2O3–SiO2

Abstract In this work, the sintering process of different glasses in the system Na 2 O–B 2 O 3 –SiO 2 has been studied. The studied compositions are suitable for sealing the gas manifolds of molten carbonate fuel cells. Sealing glasses are usually applied on the surfaces to be sealed using powder glass mixed with an organic medium. The agglomerant elimination and the sintering of the glass powder take place during the thermal treatment. Three different particle sizes of glass powder and different sintering temperatures and times have been used to reveal the influence of the specific surface area and viscosity on sintering. The control of these parameters allows optimization of the sealing conditions of the glasses. Dense materials have been characterized as well as the sintering mechanism. Two processes take place during the thermal treatment: the sintering process and the quartz crystallisation. Both processes act in opposite directions on the glass densification. Crystallisation is the dominant process at long times and high temperatures. The viscous flow Scherer model has been adequately applied to the experimental data.

Sintering behavior of lanthanide-containing glass-ceramic sealants for solid oxide fuel cells

This article reports on the influence of different lanthanides (La, Nd, Gd and Yb) on sintering behavior of alkaline-earth aluminosilicate glass-ceramic sealants for their application in solid oxide fuel cells (SOFCs). All the glasses have been prepared by the melt–quench technique. The in situ follow up of sintering behavior of glass powders has been done by a high temperature-environmental scanning electron microscope (HT-ESEM) and a hot-stage microscope (HSM) while the crystalline phase evolution and assemblage have been analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). All the glass compositions exhibit a glass-in-glass phase separation followed by two stage sintering resulting in well sintered glass powder compacts after heat treatment at 850 °C for 1 h. Diopside (CaMgSi2O6) based phases constituted the major crystalline part in glass-ceramics followed by some minor phases. The increase in lanthanide content in glasses suppressed their tendency towards devitrification, thus resulting in glass-ceramics with a high amount of residual glassy phase (50–96 wt%) which is expected to facilitate their self-healing behavior during SOFC operation. The electrical conductivity of the investigated glass-ceramics varied between (1.19 and 7.33) × 10−7 S cm−1 (750–800 °C) while the coefficient of thermal expansion (CTE) varied between (9.4 and 11.2) × 10−6 K−1 (200–700 °C). Further experimentation with respect to the long term thermal and chemical stability of residual glassy phase under SOFC operation conditions along with high temperature viscosity measurements will be required in order to elucidate the potential of these glass-ceramics as self-healing sealants.