RESUMEN
BACKGROUND: Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival when compared with limited pulmonary resection. PATIENTS AND METHODS: Data of 522 patients (64.2% men, mean age 64.5 years) who underwent pulmonary resections with curative intent for CRC metastases over a 2-year period were reviewed. All patients were followed for a minimum of 3 years. Disease-specific survival (DSS) and disease-free survival (DFS) were assessed with the Kaplan-Meier method. Factors associated with DSS and DFS were analyzed using a Cox proportional hazards regression model. RESULTS: A total of 394 (75.6%) patients underwent wedge resection, 19 (3.6%) anatomic segmentectomy, 5 (0.9%) lesser resections not described, 100 (19.3%) lobectomy, and 4 (0.8%) pneumonectomy. Accordingly, 104 (19.9%) patients were treated with major anatomic resection and 418 (80.1%) with lesser resection. Operations were carried out with video-assisted thoracoscopic surgery (VATS) in 93 patients. The overall DSS and DFS were 55 and 28.3 months, respectively. Significant differences in DSS and DFS in favor of major resection versus lesser resection (DSS median not reached versus 52.2 months, P = 0.03; DFS median not reached versus 23.9 months, P < 0.001) were found. In the multivariate analysis, major resection appeared to be a protective factor in DSS [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.41-0.96, P = 0.031] and DFS (HR 0.5, 95% CI 0.36-0.75, P < 0.001). The surgical approach (VATS versus open surgical resection) had no effect on outcome. CONCLUSION: Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results.
Asunto(s)
Neoplasias Colorrectales/cirugía , Neoplasias Pulmonares/cirugía , Metastasectomía , Recurrencia Local de Neoplasia/cirugía , Anciano , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Escisión del Ganglio Linfático/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neumonectomía/métodos , Modelos de Riesgos Proporcionales , España , Cirugía Torácica Asistida por Video/métodosRESUMEN
HIV-1 induces activation of complement through the classical and lectin pathways. However, the virus incorporates several membrane-bound or soluble regulators of complement activation (RCA) that inactivate complement. HIV-1 can also use the complement receptors (CRs) for complement-mediated antibody-dependent enhancement of infection (C-ADE). We hypothesize that hypofunctional polymorphisms in RCA or CRs may protect from HIV-1 infection. For this purpose, 139 SNPs located in 19 RCA and CRs genes were genotyped in a population of 201 Spanish HIV-1-exposed seronegative individuals (HESN) and 250 HIV-1-infected patients. Two SNPs were associated with infection susceptibility, rs1567190 in CR2 (odds ratio (OR) = 2.27, P = 1 × 10(-4)) and rs2842704 in C4BPA (OR = 2.11, P = 2 × 10(-4)). To replicate this finding, we analyzed a cohort of Italian, sexually HESN individuals. Although not significant (P = 0.25, OR = 1.57), similar genotypic proportions were obtained for the CR2 marker rs1567190. The results of the two association analyses were combined through a random effect meta-analysis, with a significant P-value of 2.6 x 10(-5) (OR = 2.07). Furthermore, we found that the protective CR2 genotype is correlated with lower levels CR2 mRNA as well as differences in the ratio of the long and short CR2 isoforms.
Asunto(s)
Infecciones por VIH/genética , Infecciones por VIH/inmunología , VIH-1/inmunología , Receptores de Complemento 3d/genética , Receptores de Complemento 3d/inmunología , Estudios de Cohortes , Susceptibilidad a Enfermedades/inmunología , Anticuerpos Anti-VIH/genética , Haplotipos , Humanos , Inmunidad Innata/genética , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
A key advance in our understanding of gene regulation came with the finding that the genome undergoes three-dimensional nuclear folding in a genetically determined process. This 3D conformation directly influences the association between enhancers and their target promoters. This complex interplay has been proven to be essential for gene regulation, and genetic variants affecting this process have been associated to human diseases. The development of new technologies that quantify these DNA interactions represented a revolution in the field. High throughput techniques like HiC provide a general picture of chromatin topology. However, they often lack resolution to evidence subtle effects that single nucleotide polymorphisms exert over the contacts between cis-regulatory regions and target promoters. Here we propose a cost-efficient approach to perform allele-specific chromatin conformation analysis. As a proof of concept, we analyzed the impact of a common deletion mapping between SIRPB1 promoter and one of its downstream enhancers.
Asunto(s)
Cromatina/metabolismo , Cromatina/fisiología , Reacción en Cadena de la Polimerasa/métodos , Alelos , Animales , ADN/genética , Variaciones en el Número de Copia de ADN/genética , Bases de Datos Genéticas , Elementos de Facilitación Genéticos/genética , Humanos , Ratones , Conformación de Ácido Nucleico , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Sitios de Carácter Cuantitativo/genética , Receptores de Superficie Celular/genéticaRESUMEN
OBJECTIVES: The Brown trout is a salmonid species with a high commercial value in Europe. Life history and spawning behaviour include resident (Salmo trutta m. fario) and migratory (Salmo trutta m. trutta) ecotypes. The main objective is to apply RNA-seq technology in order to obtain a reference transcriptome of two key tissues, brain and muscle, of the riverine trout Salmo trutta m. fario. Having a reference transcriptome of the resident form will complement genomic resources of salmonid species. DATA DESCRIPTION: We generate two cDNA libraries from pooled RNA samples, isolated from muscle and brain tissues of adult individuals of Salmo trutta m. fario, which were sequenced by Illumina technology. Raw reads were subjected to de-novo transcriptome assembly using Trinity, and coding regions were predicted by TransDecoder. A final set of 35,049 non-redundant ORF unigenes were annotated. Tissue differential expression analysis was evaluated by Cuffdiff. A False Discovery Rate (FDR) ≤ 0.01 was considered for significant differential expression, allowing to identify key differentially expressed unigenes. Finally, we have identified SNP variants that will be useful tools for population genomic studies.
Asunto(s)
Transcriptoma , Trucha , Animales , Encéfalo , Músculos , Transcriptoma/genética , Trucha/genéticaRESUMEN
OBJECTIVES: To investigate the capacity of a trained dog to identify LC in patients with malignant SPN. METHODS: We collected 90 exhaled gas samples from 30 patients with SPN (3 samples/patient). As controls we used 61 healthy volunteers and 18 COPD patients without SNP or LC, in each of whom we collected 5 exhaled gas samples (nâ¯=â¯395). The dog (Blat, a 4-year-old crossbreed between a Labrador Retriever and a Pitbull) and the methodology used were the same as previously reported by our group (see: https://drive.google.com/open?id=1R4mOtOtuZkTeb5iOEEv0K9r2kHKlPhWd). RESULTS: Of 30 patients with SPN, Blat recognized 27 of them as positive for LC and 3 as negative for LC. These results fully matched post-surgical pathological results. Sensibility was 0.97, Specificity 0.99, Positive Predictive value 0.97 and negative predictive value 0.99. The AUC of the ROC curve was 0.985. CONCLUSIONS: Trained dogs can identify accurately the malignant origin of SPN. It is now time to develop technology that can match canine olfaction and facilitate the implementation of this diagnostic approach in the clinic.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Nódulo Pulmonar Solitario/diagnóstico , Anciano , Animales , Estudios de Casos y Controles , Diagnóstico Diferencial , Modelos Animales de Enfermedad , Perros , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor/métodos , Curva ROC , Reproducibilidad de los Resultados , Nódulo Pulmonar Solitario/patologíaRESUMEN
Impulsive personality phenotype has been extensively related with genetic and hormonal factors. This study has two objectives: a) to analyse the interactions between testosterone levels and CAG repeat length polymorphism as a modulator of androgen receptor (AR) sensitivity with regard to impulsiveness traits, and b) to evaluate the contribution of other biological variables as Luteinising Hormone, Follicle Stimulating Hormone, Sex Hormone Binding Globulin (LF, FSH, SHBG) and albumin in the relationship between testosterone levels and AR CAG length polymorphism with impulsiveness. A sample of 105 healthy males (mean age 26.71±9.68 SEM) was analysed resulting in three groups of subjects according to CAG repeat lengths. Impulsiveness was measured through the Barratt's Impulsiveness Personality Scale, including three components: Motor Impulsiveness, Cognitive Impulsiveness and Non-Planning Impulsiveness. A series of ANOVAS and linear regression models predicting impulsiveness scales were conducted. Age, hormones, CAG repeat length and hormone×CAG repeat interactions were included in the regression models as independent variables. Results show that subjects with short or medium CAG repeat length tended to show higher impulsiveness phenotypes compared to long CAG repeat. The interaction between Free Testosterone and CAG, and between SHBG and CAG accounted for differences on impulsiveness (R: .47, R(2): .22 and R: .43; R(2): .18, respectively).This pattern was especially observed for the short CAG repeat group and Motor Impulsiveness.
Asunto(s)
Conducta Impulsiva/fisiología , Receptores Androgénicos/genética , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangre , Expansión de Repetición de Trinucleótido/genética , Adolescente , Adulto , Análisis de Varianza , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Inventario de Personalidad , Adulto JovenRESUMEN
To analyze Drosophila alcohol dehydrogenase gene (Adh) expression and tissue distribution at various developmental stages, we devised several immunochemical techniques making use of monoclonal antibodies against Drosophila alcohol dehydrogenase (ADH), which had been obtained previously. We here report their application to analyze the expression of Adh in a wild-type strain of D. melanogaster. s-ELISA tests were performed to evaluate fluctuations in ADH content and specific activity during development in individual organs as well as in whole individuals. In all cases, ADH specific activity appeared to be quite constant, which implies that variations in enzyme activity reflect differences in protein content. Immunoblottings of crude homogenates revealed immunoreactive low relative molecular mass peptides in addition to the 27 KD monomeric band, showing a conserved banding pattern in different organs and developmental stages. Immunohistochemical assays on whole organs were used to analyze the general pattern of ADH distribution. Immunoperoxidase staining of cryosections proved to be of crucial relevance, as it yielded full details of the tissue localization of ADH within the ADH-positive organs. We have shown not only that ADH displays a specific distribution in some organs but also that the enzyme is restricted to certain cell types.
Asunto(s)
Alcohol Deshidrogenasa/análisis , Drosophila melanogaster/enzimología , Inmunohistoquímica/métodos , Alcohol Deshidrogenasa/inmunología , Animales , Anticuerpos Monoclonales , Western Blotting , Extractos Celulares/química , Drosophila melanogaster/anatomía & histología , Secciones por Congelación , Expresión Génica , Técnicas para Inmunoenzimas , Isoenzimas/análisis , Isoenzimas/inmunología , Larva/anatomía & histología , Larva/enzimología , Distribución TisularRESUMEN
The BsmI polymorphism of the vitamin D receptor (VDR) gene influences mineral metabolism and the course of cancers and infections. The poly-A polymorphism is in linkage disequilibrium with BsmI and could be responsible for clinical associations attributed to BsmI. The objective of this work is to study the influence of VDR polymorphisms on survival of 143 prevalent hemodialysis (HD) patients followed up for 4 years. Chi-square test was used to study the association between survival and these polymorphisms. Cox analysis was performed, adjusting for comorbid conditions in the entire HD population, groups of patients on HD therapy for less than 5 and 3 years before entering 4 years of observation, patients without diabetes, and patients treated with calcitriol. Survival was analyzed by means of Kaplan-Meier according to BsmI genotypes. Results showed a strong influence of the BsmI polymorphism on survival. The bb genotype was overrepresented among survivors (45.7%) compared with nonsurvivors (21.6%), and Cox analysis showed a significant influence of age, diabetes, calcitriol treatment, and BsmI polymorphism in all groups (in the entire population, Exp(B): BB, 3.9; and Bb, 3 with respect to bb), and also of phosphorus in patients without diabetes and calcitriol-treated patients. Survival means by Kaplan-Meier were as follows: BB, 983 days; Bb, 1,152 days; and bb, 1,290 days (log-rank P = 0.01). The BsmI polymorphism influences survival in HD patients, whereas the poly-A and FokI polymorphisms do not.
Asunto(s)
Enfermedades Renales/genética , Receptores de Calcitriol/genética , Diálisis Renal , Alelos , ADN/genética , ADN/metabolismo , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Enfermedades Renales/mortalidad , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Poli A/genética , Polimorfismo Genético , Estudios Prospectivos , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
A colorimetric assay has been developed to quantify alcohol dehydrogenase (ADH) activity. The advantage of this method over conventional spectrophotometric assays is that many samples can be processed at once in a 96-well plate, monitoring the absorbance at 590 nm with a microtiter reader. ADH inhibitors have been used to show the specificity of this method. The assay offers an easy and reliable test for monitoring routine measurements of ADH activity and could be a valuable tool for those involved in the biomedical research of alcoholism, as well as in gene expression methodology in which Drosophila Adh has been widely used as reporter gene in transfection assays.
Asunto(s)
Alcohol Deshidrogenasa/análisis , Colorimetría , NAD/química , Colorimetría/instrumentación , Metosulfato de Metilfenazonio/química , Nitroazul de Tetrazolio/química , Oxidación-Reducción , EspectrofotometríaRESUMEN
Preliminary results from the Spanish cooperative group for the treatment of palmar hyperhidrosis by video-assisted thoracoscopic surgery are presented in this paper. We have reviewed the cases of all patients with this disease treated by the group, especially noting the technique, the early results and complications. Video-assisted thoracoscopy emerges as the treatment of choice, given the ease with which the thoracic sympathetic chain can be resected, its safety, the lack of observed complications, and the good short-term results.
Asunto(s)
Hiperhidrosis/cirugía , Simpatectomía , Cirugía Torácica Asistida por Video , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , EspañaRESUMEN
Impulsive-disinhibited personality (IDP) is a behavioral trait mainly characterized by seeking immediate gratification at the expense of more enduring or long-term gains. This trait has a major role in the development of several disinhibitory behaviors and syndromes, including psychopathy, attention-deficit and hyperactivity disorder, cluster-B personality disorders, criminality and alcoholism. Available data consistently support a strong heritable component, accounting for 30-60% of the observed variance in personality traits. A genome-wide analysis of copy-number variants was designed to identify novel genetic pathways associated with the IDP trait, using a series of 261 male participants with maximized opposite IDP scores. Quantitative trait locus analysis of candidate copy-number variants (CNVs) was conducted across the entire IDP continuum. Functional effects of associated variants were evaluated in zebrafish embryos. A common CNV mapping to the immune-related gene SIRPB1 was significantly associated with IDP scores in a dose-dependent manner (ß=-0.172, P<0.017). Expression quantitative trait locus analysis of the critical region revealed higher SIRPB1 mRNA levels associated with the haplotype containing the deleted allele (P<0.0007). Epigenetic marks highlighted the presence of two potential insulators within the deleted region, confirmed by functional assays in zebrafish embryos, which suggests that SIRPB1 expression rates are affected by the presence/absence of the insulator regions. Upregulation of SIRPB1 has been described in prefrontal cortex of patients with schizophrenia, providing a link between SIRPB1 and diseases involving disinhibition and failure to control impulsivity. We propose SIRPB1 as a novel candidate gene to account for phenotypic differences observed in the IDP trait.
Asunto(s)
Variaciones en el Número de Copia de ADN , Conducta Impulsiva , Inhibición Psicológica , Sitios de Carácter Cuantitativo , Receptores de Superficie Celular/genética , Adulto , Animales , Estudios de Casos y Controles , Criminales , Haplotipos , Humanos , Elementos Aisladores , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Superficie Celular/metabolismo , Pez CebraRESUMEN
Across altitudinal and latitudinal gradients, the proportion of suitable habitats varies, influencing the individual dispersal that ultimately can produce differentiation among populations. The natterjack toad (Bufo calamita) is distributed across a wide geographic range that qualifies the species as interesting for a geographic analysis of its genetic variability. Five populations of B. calamita in the Sierra de Gredos (Spain) were studied in an altitudinal gradient ranging from 750 to 2270 m using microsatellite markers. In addition, we analyzed the latitudinal genetic variation in B. calamita within a global European distribution using genetic diversity parameters (mean number of alleles per locus [M(a)] and expected heterozygosity [H(E)]) obtained from our results and those published in the literature. The low level of genetic differentiation found between populations of B. calamita (F(st) ranging from 0.0115 to 0.1018) and the decreases in genetic diversity with altitude (M(a) from 13.6 to 8.3, H(E) from 0.82 to 0.74) can be interpreted by the combined effects of discontinuous habitat, produced mainly by the high slopes barriers and geographic distance. In the latitudinal gradient, genetic diversity decreases from south to north as a consequence of the colonization of the species from the Pleistocene refugium. We conclude that the genetic variability in B. calamita along its wide altitudinal and latitudinal geographic distribution mainly reflects the colonization history of the species after the last glacial period.
RESUMEN
Since digital thoracic drainage system (DTDS) came onto the market, a number of its advantages have become clear, for example that of eliminating the differences between observers. The withdrawal of thoracic drainage has been found to be comfortable, safe and well tolerated by patients; it helps to reduce or eliminate the cost of hospital stay, because, according to the different series published in recent months, it is possible to withdraw drainage sooner and thus discharge patients earlier. Prospective studies are underway, but as yet nothing has been written about the possible benefits in outpatient surgery programmes. In this report we present our findings of 3 cases of patients undergoing pulmonary resection who were treated with continuous intra-domiciliary DTDS. Pending the results of a prospective study now underway our observation is that with properly selected patients this is a safe method.
Asunto(s)
Atención Ambulatoria , Drenaje/instrumentación , Neumonectomía , Adulto , Diseño de Equipo , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The adult body size of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), varies in natural conditions. Body size is an important fitness indicator in the Mediterranean fruit fly; larger individuals are more competitive at mating and have a greater dispersion capacity and fertility. Both temperature during larval development and host fruit quality have been cited as possible causes for this variation. We studied the influence of host fruit and temperature during larval development on adult body size (wing area) in the laboratory, and determined body size variation in field populations of the Mediterannean fruit fly in eastern Spain. Field flies measured had two origins: 1) flies periodically collected throughout the year in field traps from 32 citrus groves, during the period 2003-2007; and 2) flies evolved from different fruit species collected between June and December in 2003 and 2004. In the lab, wing area of male and female adults varied significantly with temperature during larval development, being larger at the lowest temperature. Adult size also was significantly different depending on the host fruit in which larvae developed. The size of the flies captured at the field, either from traps or from fruits, varied seasonally showing a gradual pattern of change along the year. The largest individuals were obtained during winter and early spring and the smallest during late summer. In field conditions, the size of the adult Mediterannean fruit fly seems apparently more related with air temperature than with host fruit. The implications of this adult size pattern on the biology of C. capitata and on the application of the sterile insect technique are discussed.