RESUMEN
BACKGROUND: The survival benefit of sentinel lymph node biopsy (SLNB) in immunocompetent and immunosuppressed patients with high-risk cutaneous squamous cell carcinoma (cSCC) has not been established. OBJECTIVE: To determine whether SLNB improves disease-specific survival (DSS) in high-risk cSCC. Secondary objectives were to analyse disease-free survival, nodal recurrence-free survival and overall survival (OS). METHODS: Multicentre, retrospective, observational cohort study comparing survival outcomes in immunosuppressed and immunocompetent patients treated with SLNB or watchful waiting. Inverse probability of treatment weighting was used to adjust for possible confounding effects. RESULTS: We studied 638 tumours in immunocompetent patients (SLNB n = 42, observation n = 596) and 173 tumours in immunosuppressed patients (SLNB n = 28, observation n = 145). Overall, SLNB was positive in 15.7% of tumours. SLNB was associated with a reduced risk of nodal recurrence (NR) (hazard ratio [HR], 0.05 [95% CI, 0.01-0.43]; p = 0.006), disease specific mortality (HR, 0.17 [95% CI, 0.04-0.72]; p = 0.016) and all-cause mortality (HR, 0.33 [95% CI, 0.15-0.71]; p = 0.004) only in immunocompetent patients. CONCLUSIONS: SLNB was associated with improvements in NR, DSS and OS in immunocompetent but not in immunosuppressed patients with high-risk cSCC.
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Carcinoma de Células Escamosas , Huésped Inmunocomprometido , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Masculino , Estudios Retrospectivos , Femenino , Anciano , Persona de Mediana Edad , Inmunocompetencia , Anciano de 80 o más Años , Espera Vigilante , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: In women with late preterm preeclampsia, the optimal time for delivery remains a controversial topic, because of the fine balance between the maternal benefits from early delivery and the risks for prematurity. It remains challenging to define prognostic markers to identify women at highest risk for complications, in which case a selective, planned delivery may reduce the adverse maternal and perinatal outcomes. OBJECTIVE: This trial aimed to determine whether using an algorithm based on the maternal levels of placental growth factor in women with late preterm preeclampsia to evaluate the best time for delivery reduced the progression to preeclampsia with severe features without increasing the adverse perinatal outcomes. STUDY DESIGN: This parallel-group, open-label, multicenter, randomized controlled trial was conducted at 7 maternity units across Spain. We compared selective planned deliveries based on maternal levels of placental growth factor at admission (revealed group) and expectant management under usual care (concealed group) with individual randomization in singleton pregnancies with late preterm preeclampsia from 34 to 36+6 weeks' gestation. The coprimary maternal outcome was the progression to preeclampsia with severe features. The coprimary neonatal outcome was morbidity at infant hospital discharge with a noninferiority hypothesis (noninferiority margin of 10% difference in incidence). Analyses were conducted according to intention-to-treat. RESULTS: Between January 1, 2016, and December 31, 2019, 178 women were recruited. Of those women, 88 were assigned to the revealed group and 90 were assigned to the concealed group. The data analysis was performed before the completion of the required sample size. The proportion of women with progression to preeclampsia with severe features was significantly lower in the revealed group than in the concealed group (adjusted relative risk, 0.5; 95% confidence interval, 0.33-0.76; P=.001). The proportion of infants with neonatal morbidity was not significantly different between groups (adjusted relative risk, 0.77; 95% confidence interval, 0.39-1.53; P=.45). CONCLUSION: There is evidence to suggest that the use of an algorithm based on placental growth factor levels in women with late preterm preeclampsia leads to a lower rate of progression to preeclampsia with severe features and reduces maternal complications without worsening the neonatal outcomes. This trade-off should be discussed with women with late preterm preeclampsia to allow shared decision making about the timing of delivery.
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Factor de Crecimiento Placentario/sangre , Preeclampsia/sangre , Adulto , Algoritmos , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Recién Nacido , Embarazo , Pronóstico , Espera VigilanteRESUMEN
The expression of PD-L1 on tumor cells or within the tumor microenvironment has been associated with good prognosis and sustained clinical responses in immunotherapeutic regimens based on PD-L1/PD-1/CD80 immune checkpoint blockade. To look into the current controversy in cancer immunotherapy of the relative importance of PD-L1 expression on tumor cells versus non-tumor cells of the tumor microenvironment, a hematological mouse tumor model was chosen. By combining a genetic CRISPR/Cas9 and immunotherapeutic approach and using a syngeneic hematopoietic transplantable tumor model (E.G7-cOVA tumor cells), we demonstrated that dual blockade of PD-L1 interaction with PD-1 and CD80 enhanced anti-tumor immune responses that either delayed tumor growth or led to its complete eradication. PD-L1 expression on non-tumor cells of the tumor microenvironment was required for the promotion of tumor immune escape and its blockade elicited potent anti-tumor responses to PD-L1 WT and to PD-L1-deficient tumor cells. PD-L1+ tumors implanted in PD-L1-deficient mice exhibited delayed tumor growth independently of PD-L1 blockade. These findings emphasize that PD-L1 expression on non-tumor cells plays a major role in this tumor model. These observations should turn our attention to the tumor microenvironment in hematological malignancies because of its unappreciated contribution to create a conditioned niche for the tumor to grow and evade the anti-tumor immune response.
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Anticuerpos Monoclonales/uso terapéutico , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/metabolismo , Animales , Anticuerpos Monoclonales/farmacología , Modelos Animales de Enfermedad , Humanos , Ratones , TransfecciónRESUMEN
Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR.
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Trasplante de Médula Ósea , Depleción Linfocítica , Miembro 25 de Receptores de Factores de Necrosis Tumoral/fisiología , Receptores Tipo II del Factor de Necrosis Tumoral/fisiología , Linfocitos T Reguladores/inmunología , Abatacept/farmacología , Traslado Adoptivo , Aloinjertos , Animales , Diferenciación Celular , División Celular , Rechazo de Injerto/prevención & control , Trasplante de Corazón , Homeostasis , Humanos , Tolerancia Inmunológica , Transfusión de Linfocitos , Linfopenia/etiología , Linfopenia/inmunología , Ratones , Modelos Inmunológicos , Linfocitos T Reguladores/efectos de los fármacos , Acondicionamiento Pretrasplante , Inmunología del Trasplante , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
INTRODUCTION: Vector bioimpedance analysis (BIVA) can be very useful for the evaluation of body composition, hydration, and nutritional status in infants and newborns. The objective of this study was to determine the impedance vector distribution for a group of healthy newborn Spanish children. METHODS: This was a cross-sectional, descriptive study conducted with 154 healthy, Spanish newborns (gestational age: 37-41 weeks) aged 24 to 72 hours (79 males, 75 females). Weight, height, and cephalic-circumference were determined. Resistance and reactance were measured with a single-frequency impedance analyzer at 50 kHz (tetrapolar analysis). The newborns' specific 95% confidence intervals of the mean vectors and the 95%, 75%, and 50% tolerance intervals for the individual vector measurements were plotted using R and Xc components standardized by the subjects' lengths. The mean impedance vectors were compared with Hotelling's-T2 test for vector analysis (significance level: P < .05). RESULTS: The newborns exhibited gender-related differences in the mean impedance vector (mean [SD] R/H: 833.6 [97.5] Ohm/m in males vs 918.2 [107.7] Ohm/m in females; mean [SD] Xc/H: 91.3 [34.7] Ohm/m in males vs 95.6 [23.2] Ohm/m in females). No statistically significant differences in the mean impedance vectors were observed according to days of life. Lower values of resistance and slightly higher reactance values were observed in the healthy Spanish newborns compared to Italian newborns. CONCLUSIONS: New tolerance ellipses were constructed for healthy Spanish newborns. These data allow detecting alterations in the hydration status and cell mass in term newborns in the first 3 days of life.
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Impedancia Eléctrica , Evaluación Nutricional , Estado Nutricional/fisiología , Estudios Transversales , Femenino , Humanos , Recién Nacido , Masculino , Valores de Referencia , EspañaRESUMEN
BACKGROUND: Adverse food reactions (AFRs) are defined as abnormal responses to an ingested food or food additive. Diagnosis and treatment of AFRs consist of the complete elimination of these ingredients in the dietary trial. Previous studies have demonstrated the presence of undeclared ingredients in commercial limited-antigen dry food diets that can compromise the results and efficacy of dietary elimination trails. The aim of this study was to assess a selection of commercial canine and feline dietetic limited-antigen wet foods for the potential cross-contamination of animal proteins from origins not mentioned on the label. RESULTS: Eleven canine and feline dietetic limited-antigen wet foods (9 novel animal protein foods, 1 vegetarian and 1 hydrolyzed) were analyzed by polymerase chain reaction (PCR) to detect the presence DNA of animal and vegetal origins. PCR analysis confirmed the contamination of 6 of the 11 (54.5%) limited-antigen wet diets with undeclared animal protein. One of these 6 diets was solely composed of animal protein sources completely unrelated to those declared on the label. None of the foods containing horse meat or fish were contaminated, and neither were the vegetarian or the hydrolyzed food products. Moreover, the results show that had zoological class primers only been used to check for cross-class contaminations, as are generally used in the pet food industry for in-house checks, the apparent contamination rate would have been significantly underestimated: less than 20% (3/11), instead of the actual rate of 54.7% using species-specific primers. CONCLUSION: This study reveals a high rate of cross-contamination in dietetic limited-antigen wet canine and feline foods, as previously described for dietetic dry limited-antigen foods (reported to be more than 80%). These results add new fuel to the discussion about the potential causes underlying the failure of elimination diets, since animal protein contaminants may actually be present in the commercial dietetic limited-antigen diets. AFRs may therefore occur as a result of inadequate practices in the pet food industry.
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Alimentación Animal/análisis , Contaminación de Alimentos , Reacción en Cadena de la Polimerasa/veterinaria , Animales , Aves/genética , Gatos , ADN/análisis , Dieta/veterinaria , Perros , Peces/genética , Mamíferos/genética , Plantas/genéticaRESUMEN
BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.
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Uveítis/genética , Alelos , Estudios de Casos y Controles , Femenino , Sitios Genéticos/genética , Antígenos HLA/genética , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Población Blanca/genéticaRESUMEN
Natural Killer T cells (NKT cells) are emerging as critical regulators of pro- and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA) on type I NKT cells in polyoma middle T oncogene-driven (PyMT) murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1) were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity.
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Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Receptores Inmunológicos/genética , Animales , Biomarcadores , Biomarcadores de Tumor , Neoplasias de la Mama/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Inmunofenotipificación , Recuento de Linfocitos , Ratones , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Proteína de la Leucemia Promielocítica con Dedos de Zinc/genética , Proteína de la Leucemia Promielocítica con Dedos de Zinc/metabolismo , Receptores Inmunológicos/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
OBJECTIVES: Reference values of the bioelectrical impedance vector for the Spanish child and adolescent population are needed for assessing body composition and hydration status in this population. The aim of this study is to provide reference values of the bioelectrical impedance vector in Spanish children and adolescents aged 4-18 years from Castilla y León. METHODS: This was a cross-sectional descriptive study conducted in 4401 Spanish healthy children and adolescents aged 4-18 years (2265 boys and 2136 girls). Resistance and reactance were measured with a single-frequency impedance analyzer at 50 kHz (tetrapolar analysis). The values of resistance and reactance normalized by height were used to plot the bivariate 50th, 75th, and 95th percentiles of the population by age group. Mean impedance vectors were compared with Hotelling's T2 test for vector analysis (differences being considered significant if p < .05). RESULTS: Tolerance ellipses were drawn for the Spanish child and adolescent population studied. The mean impedance vector showed displacement across all age groups except for (1) girls aged 12-13 years, (2) girls aged 15-18 years, and (3) boys aged 16-18 years. There were sex-related differences in the mean impedance vector in all age ranges, even in prepubertal children. Among adolescents, the patterns of the vector displacement were consistent with the timing of normal growth and development in all groups and are attributable to the maturation process. CONCLUSIONS: New tolerance ellipses have been constructed for Spanish children and adolescents by sex and age. These ellipses reflect the timing of normal childhood growth and development.
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Composición Corporal , Impedancia Eléctrica , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Valores de Referencia , EspañaRESUMEN
Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the surgical treatment of choice for morbid obesity. Several therapeutic options to remove common bile duct (CBD) stones have been proposed in these patients. Laparoscopy-assisted transgastric ERCP (LATERCP) has a high success rate. However, the procedure is not fully standardized and some technical variations have been proposed. We introduce two cases in which laparoscopic transgastric ERCP has been used to treat choledocholithiasis after LRYGB.
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Cirugía Bariátrica , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomía Laparoscópica/métodos , Femenino , Humanos , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Esfinterotomía EndoscópicaRESUMEN
PURPOSE: To classify and identify the main characteristics of the tools used in practice to assess the impact of elderly caregiving on the informal carers' life. METHODS: A systematic review of literature was performed searching in Embase, MEDLINE, PsycINFO, CINAHL, IBECS, LILACS, SiiS, SSCI and Cochrane Library from 2009 to 2013 in English, Spanish, Portuguese and French, and in reference lists of included papers. RESULTS: The review included 79 studies, among them several in languages other than English. Their inclusion increased the variety of identified tools to measure this impact (n = 93) and allowed a wider analysis of their geographical use. While confirming their overlapping nature, instruments were classified according to the degree of integration of dimensions they evaluated and their specificity to the caregiving process: caregiver burden (n = 20), quality of life and well-being (n = 11), management and coping (n = 21), emotional and mental health (n = 29), psychosocial impact (n = 10), physical health and healthy habits (n = 2), and other measures. A high use in practice of tools not validated yet and not caregiver-specific was identified. CONCLUSIONS: The great variety and characteristics of instruments identified in this review confirm the complexity and multidimensionality of the effects of elderly caregiving on the informal carer's life and explain the difficulties to assess these effects in practice. According to the classification provided, caregiver burden and emotional and mental health are the most evaluated dimensions. However, further work is required to develop integrated and caregiving focused procedures that can appraise this complexity across different countries and cultures.
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Cuidadores , Enfermería Geriátrica/normas , Indicadores de Calidad de la Atención de Salud , Anciano , Cuidadores/psicología , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Calidad de VidaRESUMEN
During the last years the interest in donkey milk has increased significantly mainly because of its compelling functional elements. Even if the composition and nutritional properties of donkey milk are known, its microbiota is less studied. This Research Communication aimed to provide a comprehensive characterisation of the lactic acid bacteria in raw donkey milk. RAPD-PCR assay combined with 16S rDNA sequencing analysis were used to describe the microbial diversity of several donkey farms in the North West part of Italy. The more frequently detected species were: Lactobacillus paracasei, Lactococcus lactis and Carnobacterium maltaromaticum. Less abundant genera were Leuconostoc, Enterococcus and Streptococcus. The yeast Kluyveromyces marxianus was also isolated. The bacterial and biotype distribution notably diverged among the farms. Several of the found species, not previously detected in donkey milk, could have an important probiotic activity and biotechnological potential. This study represents an important insight to the ample diversity of the microorganisms present in the highly selective ecosystem of raw donkey milk.
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Equidae/microbiología , Lactobacillaceae/clasificación , Lactobacillaceae/aislamiento & purificación , Leche/microbiología , Animales , Biodiversidad , Carnobacterium/genética , Carnobacterium/aislamiento & purificación , ADN Bacteriano/análisis , Ecosistema , Italia , Kluyveromyces/aislamiento & purificación , Lactobacillaceae/genética , Lactobacillus/genética , Lactobacillus/aislamiento & purificación , Lactococcus lactis/genética , Lactococcus lactis/aislamiento & purificación , Probióticos , ARN Ribosómico 16S/genética , Técnica del ADN Polimorfo Amplificado Aleatorio/veterinariaRESUMEN
BACKGROUND AND AIM: This article provides a practical review to undertaking safe endoscopic ampullectomy and highlights some of the common difficulties with this technique as well as offering strategies to deal with these challenges. METHODS: We conducted a review of studies regarding endoscopic ampullectomy for ampullary neoplasms with special focus on techniques. RESULTS: Accurate preoperative diagnosis and staging of ampullary tumors is imperative for predicting prognosis and determining the most appropriate therapeutic approach. The optimal technique for endoscopic ampullectomy is dependent on the lesions size. En bloc resection is recommended for lesions confined to the papilla. There is no significant evidence to support the submucosal injection before ampullectomy. There is no consensus regarding the optimal current and power output for endoscopic ampulectomy. The benefits of a thermal adjunctive therapy remain controversial. A prophylactic pancreatic stent reduces the incidence and severity of pancreatitis post-ampullectomy. CONCLUSIONS: Endoscopic ampullectomy is a safe and efficacious therapeutic procedure for papillary adenomas in experienced endoscopist and it can avoid the need for surgical intervention.
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Adenoma/cirugía , Ampolla Hepatopancreática/cirugía , Neoplasias del Conducto Colédoco/cirugía , Endoscopía Gastrointestinal/métodos , Endoscopía Gastrointestinal/efectos adversos , HumanosRESUMEN
Gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. An increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. In this work, a DNA microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. Initial validation was done with 10 different virus species, and an additional 5 species were validated using clinical samples. Detection limits of 1 × 10(3) virus particles of Human adenovirus C (HAdV), Human astrovirus (HAstV), and group A Rotavirus (RV-A) were established. Furthermore, when exogenous RNA was added, the limit for RV-A detection decreased by one log. In a small group of clinical samples from children with gastroenteritis (n = 76), the microarray detected at least one viral species in 92% of the samples. Single infection was identified in 63 samples (83%), and coinfection with more than one virus was identified in 7 samples (9%). The most abundant virus species were RV-A (58%), followed by Anellovirus (15.8%), HAstV (6.6%), HAdV (5.3%), Norwalk virus (6.6%), Human enterovirus (HEV) (9.2%), Human parechovirus (1.3%), Sapporo virus (1.3%), and Human bocavirus (1.3%). To further test the specificity and sensitivity of the microarray, the results were verified by reverse transcription-PCR (RT-PCR) detection of 5 gastrointestinal viruses. The RT-PCR assay detected a virus in 59 samples (78%). The microarray showed good performance for detection of RV-A, HAstV, and calicivirus, while the sensitivity for HAdV and HEV was low. Furthermore, some discrepancies in detection of mixed infections were observed and were addressed by reverse transcription-quantitative PCR (RT-qPCR) of the viruses involved. It was observed that differences in the amount of genetic material favored the detection of the most abundant virus. The microarray described in this work should help in understanding the etiology of gastroenteritis in humans and animals.
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Gastroenteritis/diagnóstico , Gastroenteritis/virología , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Virosis/diagnóstico , Virosis/virología , Virus/clasificación , Virus/genética , Preescolar , Gastroenteritis/epidemiología , Humanos , Lactante , Recién Nacido , Análisis de Secuencia por Matrices de Oligonucleótidos/normas , Prevalencia , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Virosis/epidemiologíaRESUMEN
Membranous CD44v6 levels in tumors and surrounding samples obtained from 94 patients with squamous cell lung carcinomas were studied and compared to clinical stage, cellular proliferation, membranous CD44v5 levels, epidermal growth factor receptor EGFR and cytoplasmatic concentrations of CYFRA 21.1. CD44v6 positive values were observed in 33/38 non-tumor samples and in 76/94 tumor samples, but there were not statistically significant differences between both subgroups. In CD44v6 positive tumor samples, CD44v6 was not associated with clinical stage, histological grade, ploidy and lymph node involvement, but significant association was found with high cellular proliferation. Likewise, CD44v6 positive tumors had significantly higher levels of EGFR and CD44v5. In patients with squamous cell lung carcinomas and clinical stage I, positive CD44v6 cases were associated with the same parameters. Furthermore, positive CD44v5 squamous tumors were associated significantly with histological grade III and lower levels of CYFRA21.1. Our findings support the value of CD44v6 as a possible indicator of poor outcome in patients with squamous lung carcinomas.
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Carcinoma de Células Escamosas/metabolismo , Membrana Celular/metabolismo , Receptores ErbB/metabolismo , Receptores de Hialuranos/metabolismo , Adulto , Anciano , Proliferación Celular/genética , Proliferación Celular/fisiología , Femenino , Humanos , Técnicas In Vitro , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
Recent evidence suggests that most influenza A virus gene segments can contribute to the pathogenicity of the virus. In this regard, the hemagglutinin (HA) subtype of the circulating strains has been closely surveyed, but the reassortment of internal gene segments is usually not monitored as a potential source of an increased pathogenicity. In this work, an oligonucleotide DNA microarray (PhyloFlu) designed to determine the phylogenetic origins of the eight segments of the influenza virus genome was constructed and validated. Clades were defined for each segment and also for the 16 HA and 9 neuraminidase (NA) subtypes. Viral genetic material was amplified by reverse transcription-PCR (RT-PCR) with primers specific to the conserved 5' and 3' ends of the influenza A virus genes, followed by PCR amplification with random primers and Cy3 labeling. The microarray unambiguously determined the clades for all eight influenza virus genes in 74% (28/38) of the samples. The microarray was validated with reference strains from different animal origins, as well as from human, swine, and avian viruses from field or clinical samples. In most cases, the phylogenetic clade of each segment defined its animal host of origin. The genomic fingerprint deduced by the combined information of the individual clades allowed for the determination of the time and place that strains with the same genomic pattern were previously reported. PhyloFlu is useful for characterizing and surveying the genetic diversity and variation of animal viruses circulating in different environmental niches and for obtaining a more detailed surveillance and follow up of reassortant events that can potentially modify virus pathogenicity.
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Dermatoglifia del ADN/métodos , Genoma Viral , Técnicas de Genotipaje/métodos , Virus de la Influenza A/clasificación , Gripe Humana/virología , Análisis por Micromatrices/métodos , Infecciones por Paramyxoviridae/veterinaria , Animales , Análisis por Conglomerados , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/aislamiento & purificación , Infecciones por Paramyxoviridae/virología , Filogenia , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Virología/métodosRESUMEN
The cosignaling network mediated by the herpesvirus entry mediator (HVEM; TNFRSF14) functions as a dual directional system that involves proinflammatory ligand, lymphotoxin that exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT; TNFSF14), and the inhibitory Ig family member B and T lymphocyte attenuator (BTLA). To dissect the differential contributions of HVEM/BTLA and HVEM/LIGHT interactions, topographically-specific, competitive, and nonblocking anti-HVEM Abs that inhibit BTLA binding, but not LIGHT, were developed. We demonstrate that a BTLA-specific competitor attenuated the course of acute graft-versus-host reaction in a murine F(1) transfer semiallogeneic model. Selective HVEM/BTLA blockade did not inhibit donor T cell infiltration into graft-versus-host reaction target organs, but decreased the functional activity of the alloreactive T cells. These results highlight the critical role of HVEM/BTLA pathway in the control of the allogeneic immune response and identify a new therapeutic target for transplantation and autoimmune diseases.
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Reacción Injerto-Huésped/inmunología , Receptores Inmunológicos/antagonistas & inhibidores , Miembro 14 de Receptores del Factor de Necrosis Tumoral/antagonistas & inhibidores , Transducción de Señal/inmunología , Traslado Adoptivo , Animales , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/trasplante , Células CHO , Movimiento Celular/genética , Movimiento Celular/inmunología , Cricetinae , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratas , Ratas Endogámicas Lew , Receptores Inmunológicos/fisiología , Miembro 14 de Receptores del Factor de Necrosis Tumoral/administración & dosificación , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Proteínas Recombinantes de Fusión/administración & dosificación , Bazo/citología , Bazo/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/trasplanteRESUMEN
Breast cancer is currently becoming a disease of the elderly. We have studied the relation between CA 15.3 serum concentrations and clinical-pathological parameters in 69 women with IDC aged over 70 years (76.3±4.2; range: 71-88; median 76). A group of 205 women with the same tumor but aged <70 years (62.8±4.0; range: 55-70; median 63) was also considered for comparison. Tumor size, axillary lymph node involvement, distant metastasis and histological grade were taken account. Serum CA 15.3 was determined by luminescence assay. CA 15.3 serum concentrations ranged between 6 and 85 U/mL (median 22.9 U/mL), and were higher only in patients with greater (qualitative and quantitative; p: 0.041) tumor size. Our results show that in women with IDCs, and aged over 70 years, serum CA 15.3 serum concentrations are associated exclusively with a greater tumor size, being these findings different to those described in women with the same subtype of tumor considered as a whole or with lower age.
Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Antígeno Carcinoembrionario/sangre , Carcinoma Ductal/diagnóstico , Mediciones Luminiscentes , Mucina-1/sangre , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Carcinoma Ductal/patología , Femenino , Humanos , Metástasis Linfática , Clasificación del TumorRESUMEN
CD103 (alpha(E)) integrin expression distinguishes a population of dendritic cells (DCs) that can be found in many if not all lymphoid and non-lymphoid organs. CD103(+) DCs display distinct functional activities. Migratory CD103(+) DCs derived from skin, lung, and intestine efficiently present exogenous antigens in their corresponding draining lymph nodes to specific CD8(+) T cells through a mechanism known as cross-presentation. On the T cells they prime, intestinal CD103(+) DCs can drive the induction of the chemokine receptor CCR9 and alpha(4)beta(7) integrin, both known as gut-homing receptors. CD103(+) DCs also contribute to control inflammatory responses and intestinal homeostasis by fostering the conversion of naive T cells into induced Foxp3(+) regulatory T cells, a mechanism that relies on transforming growth factor-beta and retinoic acid signaling. This review discusses recent findings that identify murine CD103(+) DCs as important regulators of the immune response.
Asunto(s)
Antígenos CD/inmunología , Diferenciación Celular , Linaje de la Célula , Células Dendríticas/inmunología , Cadenas alfa de Integrinas/inmunología , Animales , Presentación de Antígeno , Cadherinas/inmunología , Diferenciación Celular/inmunología , Linaje de la Célula/inmunología , Homeostasis , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Células de Langerhans/inmunología , Pulmón/citología , Pulmón/inmunología , Ganglios Linfáticos Agregados/citología , Ganglios Linfáticos Agregados/inmunología , Transducción de Señal , Bazo/citología , Bazo/inmunología , Linfocitos T/inmunologíaRESUMEN
OBJECTIVES: The objective of this work was to establish the analgesia protocols for different types of urological surgery and to analyze the impact on pain during the first 24 h after surgery. METHODS: The study included 186 patients undergoing urological surgery between 2011 and 2013. Seven analgesia protocols were established and applied according to the surgical procedure. At 24 h post-surgery, i.e., the initiation of analgesic treatment, patients` pain was evaluated by visual analog scale/numeric scale (VAS/NS), and their degree of satisfaction and nausea were assessed. RESULTS: The study sample comprised 137 males (73.7%) and 49 females (26.3%), with a mean age of 58.5 ± 14.7 yrs. Analgesia protocol 1 was applied in 5.9% of patients, protocol 2 in 17.8%, protocol 3 in 8.6%, protocol 4 in 38.9%, protocol 5 in 13.5%, protocol 6 in 14.6%, and protocol 7 in 0.5%. At 24 h post-surgery, the VAS/NS score was = 3 in 82.3% of patients; hence, only 17.7% required rescue analgesia; 71% of patients were highly satisfied with the treatment provided and 22.6% were satisfied. 6.4% were not satisfied. CONCLUSION: Establishing analgesia protocols according to the type of surgery is a valid and useful measure to control postoperative pain during the first 24 h and to provide appropriate treatment standardization and follow-up.