CD209 in inflammatory bowel disease: a case-control study in the Spanish population

<p>Abstract</p> <p>Background</p> <p>The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The <it>CD209 </it>gene is located in a region linked previously to IBD and a <it>CD209 </it>functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this <it>CD209 </it>variant in IBD susceptibility.</p> <p>Methods</p> <p>We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the <it>CD209 </it>single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using χ²tests.</p> <p>Results</p> <p>No association between <it>CD209 </it>and UC or CD was observed initially. However, stratification of UC patients by <it>HLA-DR3 </it>status, a strong protective allele, showed that carriage of the <it>CD209</it>_G allele could increase susceptibility in the subgroup of <it>HLA-DR3</it>-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04–3.02, <it>vs. </it>controls).</p> <p>Conclusion</p> <p>A functional variant in the <it>CD209 </it>gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in <it>HLA-DR3</it>-positive individuals but further studies are necessary.</p

Geochemistry of As-, F- and B-bearing waters in and around San Antonio de los Cobres, Argentina, and implications for drinking and irrigation water quality

Spring, stream and tap waters from in and around San Antonio de los Cobres, Salta, Argentina, were sampled to characterize their geochemical signatures, and to determine whether they pose a threat to human health and crops. The spring waters are typical of geothermal areas world-wide, in that they are Na-Cl waters with high concentrations of Astot, As(III), Li, B, HCO3, F and SiO2 (up to 9.49, 8.92, 13.1, 56.6, 1250, 7.30 and 57.2 mg L-1, respectively), and result from mixing of deep Na-Cl brines and meteoric HCO3-rich waters. Springs close to the town of San Antonio have higher concentrations of all elements, and are generally cooler, than springs in the Baños de Agua Caliente. Spring water chemistry is a result of mixing of deep Na-Cl brines and meteoric HCO3 waters. Stream waters are also Na-Cl type, and receive large inputs of all elements from the springs near San Antonio, but concentrations decrease downstream through the town of San Antonio due to mineral precipitation. The spring that is used as a drinking water source, and other springs in the area, have As, F and B concentrations in excess of WHO and Argentinian drinking water guidelines. Evaluation of the waters for irrigation purposes suggests that their high salinities and B concentrations may adversely affect crops. The waters may be improved for drinking and irrigation by dilution with cleaner meteoric waters, mineral precipitation or by use of commercial filters. Such recommendations could also be followed by other settlements that draw drinking and irrigation waters from geothermal sources

A modo de epílogo. La Ría de Huelva: conclusiones y perspectivas

Ejemplar dedicado a: Ritos de paso y puntos de paso: la ría de Huelva en el mundo del Bronce Final europeo / coord. por Marisa Ruiz-Gálvez PriegoLa Ría parece haberse depositado en un lapso relativamente breve, en torno al s. X a.C., como parece desprenderse de los test de igualdad de medios y de varianza, realizados por Angel Rodríguez Alcalde. Ello vendría asimismo avalado por las dataciones des. IX a.C., para los inicios de la colonización fenicia del Mediodía peninsular. Por criterios tipológicos y de cultura material, habría que aceptar idénticas dataciones, entre los s. X a VIII a.C. para los castros portugueses de Baióes y Coto da Pena y para la fase de Bronce Final del asentamiento levantino de Peña Negra.Peer reviewe

A modo de epílogo. La Ría de Huelva: conclusiones y perspectivas

Ejemplar dedicado a: Ritos de paso y puntos de paso: la ría de Huelva en el mundo del Bronce Final europeo / coord. por Marisa Ruiz-Gálvez PriegoLa Ría parece haberse depositado en un lapso relativamente breve, en torno al s. X a.C., como parece desprenderse de los test de igualdad de medios y de varianza, realizados por Angel Rodríguez Alcalde. Ello vendría asimismo avalado por las dataciones des. IX a.C., para los inicios de la colonización fenicia del Mediodía peninsular. Por criterios tipológicos y de cultura material, habría que aceptar idénticas dataciones, entre los s. X a VIII a.C. para los castros portugueses de Baióes y Coto da Pena y para la fase de Bronce Final del asentamiento levantino de Peña Negra.Peer reviewe

Ovine Fetal Immune Response to Cache Valley Virus Infection

Cache Valley virus (CVV)-induced malformations have been previously reproduced in ovine fetuses. To evaluate the development of the antiviral response by the early, infected fetus, before the development of immunocompetency, ovine fetuses at 35 days of gestation were inoculated in utero with CVV and euthanized at 7, 10, 14, 21, and 28 days postinfection. The antiviral immune response in immature fetuses infected with CVV was evaluated. Gene expression associated with an innate, immune response was quantified by real-time quantitative PCR. The upregulated genes in infected fetuses included ISG15, Mx1, Mx2, IL-1, IL-6, TNF-α, TLR-7, and TLR-8. The amount of Mx1 protein, an interferon-stimulated GTPase capable of restricting growth of bunyaviruses, was elevated in the allantoic and amniotic fluid in infected fetuses. ISG15 protein expression was significantly increased in target tissues of infected animals. B lymphocytes and immunoglobulin-positive cells were detected in lymphoid tissues and in the meninges of infected animals. These results demonstrated that the infected ovine fetus is able to initiate an innate and adaptive immune response much earlier than previously known, which presumably contributes to viral clearance in infected animals

Energy Reconstruction of Electromagnetic Showers from π0 Decays with the ICARUS T600 Liquid Argon TPC

We discuss the ICARUS T600 detector capabilities in electromagnetic shower reconstruction through the analysis of a sample of 212 events, coming from the 2001 Pavia surface test run, of hadronic interactions leading to the production of π0 mesons. Methods of shower energy and shower direction measurements were developed and the invariant mass of the photon pairs was reconstructed. The (γ,γ) invariant mass was found to be consistent with the value of the π0 mass. The resolution of the reconstructed π0 mass was found to be equal to 27.3%. An improved analysis, carried out in order to clean the full event sample from the events measured in the crowded environment, mostly due to the trigger conditions, gave a π0 mass resolution of 16.1%, significantly better than the one evaluated for the full event sample. The trigger requirement of the coincidence of at least four photo-multiplier signals favored the selection of events with a strong pile up of cosmic ray tracks and interactions. Hence a number of candidate π0 events were heavily contaminated by other tracks and had to be rejected. Monte Carlo simulations of events with π0 production in hadronic and neutrino interactions confirmed the validity of the shower energy and shower direction reconstruction methods applied to the real data.We are glad of the financial and technical support of our funding agencies and in particular of the Istituto Nazionale di Fisica Nucleare (INFN). The Polish groups acknowledge the support of the Ministry of Science and Higher Education in Poland, 105,160,620,621/E-344,E-340,E-77,E-78/SPB/ICARUS/ P-03/DZ211-214/2003-2008, 1P03B04130 and N N202 0299 33

Detection of lymph node metastasis in lung cancer patients using a one-step nucleic acid amplification assay: a single-centre prospective study

BACKGROUND: The use of one-step nucleic acid amplification (OSNA) allows for lymph node (LN) metastasis to be detected rapidly and accurately. We conducted a prospective single-centre clinical trial to evaluate OSNA assay in detecting LN metastasis of lung cancer. PATIENTS AND METHODS: A total of 705 LNs from 160 patients with clinical stage IA to IVA lung cancer were included in this study. The LNs were divided and submitted to routine histological diagnosis and OSNA assay and the results were compared. We also examined keratin 19 expression of different histological types lung primary tumours. RESULTS: When the cut-off value was set to 250 copies/microl, the concordance rate between the two methods was 96.17% and the sensitivity 97.14%. Discordant results were observed in 27 LNs of 21 patients. Most of these discordant results were molecular micrometastasis expressing a very low number of copies with negative histology. Most thoracic tumours were positive for keratin 19. CONCLUSIONS: Our data show that the OSNA assay might be a useful and sensitive method to diagnose LN metastasis in lung cancer and could be applied to intraoperative decision-making in personalised lung cancer surgery based on LN status and a more accurate staging of patients

Growth Hormone Reprograms Macrophages toward an Anti-Inflammatory and Reparative Profile in an MAFB-Dependent Manner

Growth hormone (GH), a pleiotropic hormone secreted by the pituitary gland, regulates immune and inflammatory responses. In this study, we show that GH regulates the phenotypic and functional plasticity of macrophages both in vitro and in vivo. Specifically, GH treatment of GM-CSF–primed monocyte–derived macrophages promotes a significant enrichment of anti-inflammatory genes and dampens the proinflammatory cytokine profile through PI3K-mediated downregulation of activin A and upregulation of MAFB, a critical transcription factor for anti-inflammatory polarization of human macrophages. These in vitro data correlate with improved remission of inflammation and mucosal repair during recovery in the acute dextran sodium sulfate–induced colitis model in GH-overexpressing mice. In this model, in addition to the GH-mediated effects on other immune cells, we observed that macrophages from inflamed gut acquire an anti-inflammatory/reparative profile. Overall, these data indicate that GH reprograms inflammatory macrophages to an anti-inflammatory phenotype and improves resolution during pathologic inflammatory responses.This work was supported in part by grants from the Spanish Ministry of Science, Innovation and Universities (SAF2017-82940-R Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional (AEI/FEDER), Unión Europea [UE] [to M.M.], SAF2017-83785-R AEI/FEDER, UE [to Á.L.C.] and FJCI-2016-29990 AEI/FEDER, UE [to B.S.P.]), from the Redes Temáticas de Investigación Cooperativa en Salud Program of Instituto de Salud Carlos III (RD12/0012/0006 and RD12/0012/0007, Red de Investigación en Inflamación y Enfermedades Reumáticas), and the Regional Government of Madrid (B2017/BMD-3804 [to C.M.-A.])

Interleukin-10 polymorphisms in Spanish IgA deficiency patients: a case-control and family study

BACKGROUND: IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. Genetic and environmental factors are suspected to be involved in the development of the disease. Interleukin-10 (IL-10) is a cytokine with stimulatory activity on immunoglobulin production and it may be an important regulator in IgAD pathogenesis. The IL-10 gene contains several single nucleotide polymorphisms (SNPs) and two polymorphic microsatellites located in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers are associated or linked to IgAD in Spanish patients. METHODS: We genotyped 278 patients with IgAD and 573 ethnically matched controls for the microsatellites IL-10R and IL-10G and for three single nucleotide polymorphisms at positions -1082, -819 and -592 in the proximal promoter of the gene. We also included in this study the parents of 194 patients in order to study the IL-10 haplotypes transmitted and not transmitted to the affected offspring. RESULTS: The only allele where a significant difference was observed in the comparison between IgA deficiency patients and controls was the IL-10G12 allele (OR = 1.58 and p = 0.021). However, this p value could not withstand a Bonferroni correction. None of the IL-10R or promoter SNP alleles was found at a different frequency when patients were compared with controls. CONCLUSION: Our data do not show any significant difference in IL-10 polymorphism frequencies between control and IgAD patient samples. Their haplotype distribution among patients and controls was also equivalent and therefore these microsatellites and SNPs do not seem to influence IgAD susceptibility