RESUMEN
The role of bedside assistants in robot-assisted minimally invasive esophagectomy is important. It includes knowledge of the procedure, knowledge of the da Vinci Surgical System, skills in laparoscopy, and good communicative skills. An experienced bedside assistant will likely improve efficiency and safety of robot-assisted minimally invasive esophagectomy.
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Boehmeria , Neoplasias Esofágicas , Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias Esofágicas/cirugía , Esofagectomía , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD. DESIGN: As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR. RESULTS: Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium). CONCLUSIONS: The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.
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Enfermedad Celíaca/genética , Antígenos HLA-DQ/genética , Intestinos/microbiología , Microbiota/genética , Enfermedad Celíaca/microbiología , Clostridium/genética , Heces/microbiología , Femenino , Marcadores Genéticos/genética , Genotipo , Haplotipos/genética , Humanos , Lactante , Masculino , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de RiesgoRESUMEN
Alterations in intestinal epithelial permeability could underlie inflammatory bowel disease (IBD) and celiac disease (CeD) etiology, as supported by previous association studies. One related gene, DLG5 [discs, large homologue 5 (Drosophila)], has been associated with IBD in several populations and with CeD in the Dutch population. We tried to confirm the involvement of DLG5 in CeD performing a case-control study (725 CeD patients and 803 controls) by analysing the R30Q variant (rs1248696). Genetic frequencies did not significantly differ between groups (P > 0.80) and the meta-analysis with the Dutch data did not show any association. Additionally, we evaluated the effect of R30Q in IBD risk (858 patients), as discordant results were previously obtained. No association was detected. Our study does not support the effect of the R30Q DLG5 variant in CeD or IBD predisposition in the Spanish population.
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Enfermedad Celíaca/genética , Enfermedades Inflamatorias del Intestino/genética , Proteínas de la Membrana/genética , Proteínas Supresoras de Tumor/genética , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , EspañaAsunto(s)
Enfermedad Celíaca/inmunología , Harina/efectos adversos , Triticum/efectos adversos , Hipersensibilidad al Trigo/inmunología , Antialérgicos/uso terapéutico , Biomarcadores/sangre , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/dietoterapia , Niño , Preescolar , Dieta Sin Gluten , Femenino , Glútenes/efectos adversos , Glútenes/inmunología , Humanos , Inmunoglobulina E/sangre , Lactante , Pruebas Intradérmicas , Masculino , Triticum/inmunología , Hipersensibilidad al Trigo/sangre , Hipersensibilidad al Trigo/diagnóstico , Hipersensibilidad al Trigo/tratamiento farmacológicoRESUMEN
Coeliac disease (CD) development involves genetic (HLA-DQ2/DQ8) and environmental factors. Herein, the influence of the HLA-DQ genotype on the gut colonization process of breast-fed children was determined. A cohort of 20 newborns, with at least one first-degree relative with CD, were classified according to their HLA-DQ genotype into high, intermediate and low genetic risk groups, showing 24-28%, 7-8% and less than 1% probability to develop CD, respectively. Faecal microbiota was analysed at 7 days, 1 and 4 months of children's age by fluorescence in situ hybridization. When considering all data, Gram-negative bacteria and Bacteroides-Prevotella group proportions were higher (P<0.05) in the high than in the intermediate and low genetic risk groups. E. coli, Streptococcus-Lactococcus, E. rectale-C. coccoides, sulphate-reducing bacteria, C. lituseburense and C. histolyticum group proportions were also significantly higher (P<0.05) in the high than in the low genetic risk group. Correlations between these bacterial groups and the genetic risk were also detected (P<0.05). In addition, the number and type of CD relative seemed to influence (P<0.050) these bacterial proportions in children at CD risk. At 4 months of age, similar relationships were established between the high genetic risk to develop CD and the proportions of Streptococcus-Lactococcus (P<0.05), E. rectale-C. coccoides (P<0.05), C. lituseburense (P<0.05), C. histolyticum (P<0.05), Bacteroides-Prevotella (P<0.10) groups and total Gram-negative bacteria (P<0.05). The results suggest a relationship between HLA-DQ genes and the gut microbial colonization process that could lead to a change in the way this disorder is investigated.
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Antígenos HLA-DQ/genética , Intestinos/microbiología , Bacteroides/crecimiento & desarrollo , Bacteroides/aislamiento & purificación , Citometría de Flujo , Genotipo , Cadenas alfa de HLA-DQ , Cadenas beta de HLA-DQ , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Lactococcus/crecimiento & desarrollo , Lactococcus/aislamiento & purificación , Prevotella/crecimiento & desarrollo , Prevotella/aislamiento & purificación , Streptococcus/crecimiento & desarrollo , Streptococcus/aislamiento & purificaciónRESUMEN
Infants diagnosed with allergy to cow's milk protein (CMP) are fed extensively hydrolysed cow's milk formulas, modified soy formulas or even amino acid-based formulas. Hydrolysed rice protein infant formulas have become available and have been shown to be well tolerated by these infants. A prospective open, randomized clinical study to compare the clinical tolerance of a new hydrolysed rice protein formula (HRPF) with an extensively hydrolysed CMP formula (EHF) in the feeding of infants with IgE-mediated cow's milk allergy. Ninety-two infants (46 boys and 46 girls, mean age 4.3 months, range 1.1-10.1 months) diagnosed with IgE-mediated cow's milk allergy were enrolled in the study. Clinical tolerance to the formula products was tested. Clinical evaluation included skin prick tests with whole cow's milk, soya and rice as well as antigens of CMP (beta-lactoglobulin, alpha-lactalbumin, casein and bovine seroalbumin), HRPF and EHF and specific IgE determinations to CMP using CAP technology. Patients were randomized to receive either an EHF based on CMP or a new HRPF. Follow-up was at 3, 6, 12, 18 and 24 months. Growth parameters were measured at each visit. One infant showed immediate allergic reaction to EHF, but no reaction was shown by any infant in the HRPF group. The number of infants who did not become tolerant to CMP during the study was not statistically different between the two groups. Measurement of IgE levels of infants allergic to CMP during the study showed no significant differences between the two formula groups. Growth parameters were in the normal range and similar between groups. In this study, the HRPF was well tolerated by infants with moderate to severe symptoms of IgE-mediated CMP allergy. Children receiving this formula showed similar growth and development of clinical tolerance to those receiving an EHF. In accordance with current guidelines, this HRPF was tolerated by more than 90% of children with CMP allergy and therefore could provide an adequate and safe alternative to CMP-hydrolysed formulas for these infants.
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Alérgenos/efectos adversos , Fórmulas Infantiles/administración & dosificación , Hipersensibilidad a la Leche/dietoterapia , Proteínas de la Leche/efectos adversos , Proteínas de Vegetales Comestibles/administración & dosificación , Hidrolisados de Proteína/administración & dosificación , Animales , Bovinos , Femenino , Estudios de Seguimiento , Humanos , Tolerancia Inmunológica , Inmunoglobulina E/sangre , Lactante , Fórmulas Infantiles/química , Masculino , Hipersensibilidad a la Leche/sangre , Hipersensibilidad a la Leche/diagnóstico , Hipersensibilidad a la Leche/fisiopatología , Oryza/inmunología , Proteínas de Vegetales Comestibles/efectos adversos , Proteínas de Vegetales Comestibles/química , Estudios Prospectivos , Hidrolisados de Proteína/efectos adversos , Hidrolisados de Proteína/química , Pruebas CutáneasRESUMEN
BACKGROUND AND AIMS: Genome-wide association studies in coeliac disease (CD) have resulted in the finding of eight new genetic regions associated with disease susceptibility. However, a replication study performed in the Italian population could not confirm two of those new regions: 2q12 (IL18RAP) and 3p21 (CCR3). The aim of this study was to investigate the role of those regions in CD risk in a different Mediterranean population, the Spanish population. METHODS: A case-control study with 722 patients with CD and 794 ethnically matched healthy controls was performed. Two single-nucleotide polymorphisms, rs917997 (2q12) and rs6441961 (3p21), were genotyped and their genetic frequencies were compared between both groups using the chi(2) test. RESULTS: An association was found with rs6441961 (p = 0.0004, OR = 1.32, 95% CI 1.13 to 1.54). A non-significant result (but concordant with the initial study) was obtained for rs917997. CONCLUSION: The association of the 3p21 genetic region with CD susceptibility in the Spanish population was confirmed. In 2q12, the initially described OR is most probably overestimated and therefore the real situation may be the existence of a genuine but weak risk factor, which generates statistical power limitations.
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Enfermedad Celíaca/genética , Subunidad beta del Receptor de Interleucina-18/genética , Receptores CCR3/genética , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Niño , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genoma Humano , Humanos , Masculino , Polimorfismo de Nucleótido Simple , EspañaRESUMEN
Celiac disease (CD) is an inflammatory condition affecting small bowel and triggered by gluten (or related proteins) ingestion in genetic susceptible individuals. Polymorphisms in three genes, SERPINE2, PPP6C and PBX3, have recently been associated with CD in the Spanish population. However, this association could not be replicated in the UK population using imputed data. As this second study analyzed a different population, we aimed at reevaluating the role of those polymorphisms using an independent Spanish sample. We genotyped three single nucleotide polymorphisms: rs6747096 in SERPINE2, rs458046 in PPP6C and rs7040561 in PBX3, in 417 CD patients, 527 ethnically matched healthy controls and parents of 304 CD patients. A case-control study using the chi(2)-test and a familial study using the transmission disequilibrium test were performed. No association was detected in those analyses. Therefore, our results seem to discard the role of the previously described polymorphisms in SERPINE2, PPP6C and PBX3 in CD susceptibility.
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Precursor de Proteína beta-Amiloide/genética , Enfermedad Celíaca/genética , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Fosfoproteínas Fosfatasas/genética , Proteínas Proto-Oncogénicas/genética , Receptores de Superficie Celular/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Genotipo , Humanos , Polimorfismo de Nucleótido Simple/genética , Nexinas de Proteasas , Serpina E2RESUMEN
Celiac disease (CD) is a multifactorial disease characterized by intestinal inflammation after gluten exposure in genetically susceptible individuals. A strong influence of certain human leukocyte antigen (HLA) alleles (those coding the HLA-DQ2 and DQ8 heterodimers) is well established, but they cannot explain the overall genetic risk. CIITA could be a good candidate gene for CD because it is mainly transcriptionally regulated, and it encodes the master regulator of major histocompatibilty complex class II gene transcription. CIITA is located in 16p13, a region also containing KIAA0350 (CLEC16A), associated with two autoimmune diseases in genome-wide association studies. We aimed at studying the involvement of polymorphisms in CIITA and KIAA0350 in CD susceptibility, with special attention to evaluate the possible presence of more than one risk factor in the region. We performed a case-control study with 607 CD patients and up to 794 healthy controls, all Spaniards. All samples were genotyped for five single nucleotide polymorphisms: rs3087456 (-168A/G) and rs4774 in CIITA and rs7203459, rs6498169 and rs2903692 in KIAA0350. No significant results were obtained when comparing genotypic, allelic or haplotypic frequencies between patients and controls. Our results seem to discard the influence in CD susceptibility of CIITA and KIAA0350 markers previously associated with other autoimmune diseases.
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Enfermedades Autoinmunes/genética , Enfermedad Celíaca/genética , Lectinas Tipo C/genética , Proteínas de Transporte de Monosacáridos/genética , Proteínas Nucleares/genética , Transactivadores/genética , Alelos , Estudios de Casos y Controles , Enfermedad Celíaca/inmunología , Susceptibilidad a Enfermedades , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Lectinas Tipo C/metabolismo , Desequilibrio de Ligamiento , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleótido Simple , Transactivadores/metabolismoRESUMEN
BACKGROUND: In Spain, there are some organizations and scientific societies that have edited reference values of recommended nutrient intake, but whose data does not always agree in terms of format and content. AIMS: To review the definitions, data and methodology that other countries or groups of countries have followed to obtain and document their own reference values in order to offer basic information to facilitate the establishment of the best reference values for the Spanish population. FIELD: Review of the available information in different countries (or groups of countries) from the European Union, the United States and World Health Organization. The analysed data concerned to healthy populations. CONCLUSIONS: Reference intakes differ among the examined countries according to population groups, included nutrients, methodology and frequency of published reviews. However, most of the countries define major concepts in the same way, although with different names in each country. On the other hand, most of the studied cases represent only a scientific organization in charge of the publication and update of the values of dietary reference intakes, but not in Spain. In that context, it looks convenient to reach a consensus among all Spanish organizations and scientific societies that are involved in this task, in order to establish an acceptable reference values.
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Dieta , Ingestión de Alimentos , Organización Mundial de la Salud , Europa (Continente) , Humanos , Valores de Referencia , Estados UnidosRESUMEN
Recent studies have shown association of the IL23R gene with inflammatory bowel disease, psoriasis and ankylosing spondylitis. We aimed at studying the involvement of IL23R in celiac disease (CD) and multiple sclerosis (MS). We performed a case-control study including 598 patients with CD, 414 with MS and 546 healthy controls, all of them white Spaniards. All samples were genotyped for two single nucleotide polymorphisms: rs7517847 and rs11209026 (Arg381Gln). Statistical analyses were performed using chi(2-)tests or the Fisher's exact test. The minor allele (Gln) of the coding variant Arg381Gln was significantly increased in CD and MS patients when compared to controls (8% in CD vs 6% in controls, P=0.02; 9% in MS, P=0.006). In MS, a stronger effect was observed in patients showing primary-progressive disease (16%, P=0.004). Moreover, heterozygotes for rs7517847 were significantly increased in this group of MS patients (81% in MS vs 48% in controls, P=0.0002). In conclusion, contrary to what has been described previously, the less frequent allele of the functional polymorphism Arg381Gln (rs11209026) seems to be increasing susceptibility to CD and MS, although in this last group of patients a stronger effect is observed in patients affected of a primary-progressive form.
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Enfermedad Celíaca/genética , Predisposición Genética a la Enfermedad , Esclerosis Múltiple/genética , Receptores de Interleucina/genética , Alelos , Estudios de Casos y Controles , Enfermedad Celíaca/patología , Distribución de Chi-Cuadrado , Frecuencia de los Genes , Variación Genética , Haplotipos , Heterocigoto , Humanos , Esclerosis Múltiple/patología , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVE: [corrected] Our aim was to analyze our results in the management of intestinal failure with a multidisciplinary approach including optimized parenteral nutrition, reconstructive surgery and intestinal transplantation (ITx). MATERIAL AND METHODS: We included all patients evaluated by our team with the diagnosis of IF. We assessed outcome, mortality and complications in children that achieved adaptation and those listed for ITx. RESULTS: Seventy one children (40 boys, 31 girls) were evaluated between 1997 and 2006 because of IF. Forty eight (76%) were referred from other institutions. In 56 cases (80%) IF began in the newborn period. Causes of IF were: short bowel syndrome (52) intestinal motility disorders (16) and intestinal epithelial disorders (3). Median birth weight in the group of SBS was 2.2 Kg and prematurity was an associated condition in 15% of them. Overall, fourteen patients (20%) achieved intestinal adaptation with progressive weaning from PN, the management of these children consisted of optimized parenteral and enteral nutrition and autologous intestinal reconstructive surgery. Nine (13%) are stable under home parenteral nutrition regimen. Eight children (11%), all of them listed for liver and small bowel transplantation, died in the waiting list after a mean waiting time of more than 300 days, with a median of 4 laparotomies and 4 episodes of catheter related sepsis. Four children (5.6%) died in the adaptation process or before their inclusion on the waiting list. Finally, twenty five (35,2%) children underwent 28 intestinal transplantation: 9 isolated small bowel transplantation (SBTx), 16 combined liver and small bowel (CLSB) and 3 multivisceral (MVTx). Among transplanted patients, 9 (36%) died, (3 MVTx, 1 SBTx and 8 CLSB) and four were retransplanted. CONCLUSIONS: Intestinal Transplantation is an established alternative to parenteral nutrition in the treatment of IF, although complications and mortality rates are still considerable, especially MVTx and CLSBTx. Mortality in children listed for intestinal transplantation remains also high. Intestinal adaptation can be achieved with adequate rehabilitation therapy even in some cases with apparently irreversible intestinal transplantation. Early referral before liver failure or other complications arise is crucial is crucial in order to improve the outcome of these patients.
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Síndromes de Malabsorción , Femenino , Humanos , Lactante , Recién Nacido , Síndromes de Malabsorción/complicaciones , Síndromes de Malabsorción/mortalidad , Síndromes de Malabsorción/terapia , Masculino , Grupo de Atención al PacienteRESUMEN
Resumen Los biobancos son una innovadora herramienta biotecnológica y un recurso fundamental para el continuo avance en la investigación científica biomédica, y para el advenimiento de la medicina de precisión. Se han desarrollado de forma exponencial durante los últimos 20 años en el mundo, como también a nivel de nuestro país, con la creación de 10 biobancos desde el año 2004. En ellos se almacenan y organizan distintos tipos de muestras biológicas, asociadas a datos epidemiológicos y genéticos de donantes voluntarios. Todos los especímenes almacenados deben ser preservados con estándares de calidad garantizados, a modo de asegurar trazabilidad, integridad y calidad de las muestras. A pesar de que la mantención de un biobanco puede significar altos costos, a fin de cuentas, abaratan costos de los estudios clínicos, dado que es precisamente el biobanco quien se encarga de la obtención de datos y muestras clínicas confiables, permitiendo realizar múltiples estudios a partir de las mismas muestras. A través de este proceso, los biobancos permiten mantener una fuente confiable de recur-sos para la investigación en diversas áreas de la medicina, dentro de ellas la otorrinolaringología. En otorrinolaringología, los biobancos han significado un gran avance, facilitando la investigación en relación con hipoacusia, presbiacusia y tinnitus, así como en el área oncológica. En un futuro, se espera que la comunidad científica haga uso de este recurso, pudiendo expandir su utilidad no solo en el área médica, sino también en otras profesiones de la salud, maximizando así su gigantesco potencial.
Abstract Biobanks are novel biotechnological tools and a fundamental resource for the constant development of biomedical research, as much as for the growing practice of precision medicine. They have proliferated worldwide over the past 20 years and Chile has not been left behind with the creation of 10 bio-banks since 2004. Biobanks store and organize different types of biological samples associated with epidemiological and genetic data from volunteer donors. These samples are stored and preserved under guaranteed quality standards to ensure their traceability, integrity, and quality. Even though the price of maintaining a biobank may seem high, after all, they reduce the costs of research, since biobanks are responsible of the acquisition and storage of data and samples, allowing the performance of multiple studies from the same collection of specimens. In this direction, biobanks grant a constant source of well-founded scientific material for investigation in a wide range of medical fields, such as otolaryngology among them. In otolaryngology, the biobanks have meant a great improvement, facilitating investigations related to deafness, presbycusis, tinnitus and oncology. In the future we hope the scientific community will expand the use this innovative tool over a broader medical field and towards other health-related professions, making the most of its enormous potential.
Asunto(s)
Humanos , Otolaringología , Bancos de Muestras Biológicas/organización & administración , Bancos de Muestras Biológicas/tendencias , Medicina de Precisión , Chile/epidemiologíaRESUMEN
AIM: To address the role of CD209 in celiac disease (CD) patients. Non-human leukocyte antigen (HLA) genetic factors in CD predisposition are poorly understood, and environmental factors like infectious pathogens may play a role. CD209 is a dendritic and macrophage surface molecule involved in pathogen recognition and immune activation. Recently, a functional variant in the promoter of the CD209 gene (-336A/G) has been shown to affect the transcriptional CD209 activity in vitro and it has been associated with a higher susceptibility to/or severity of infection. METHODS: The study population was composed of two case-control cohorts of 103 and 386 CD patients and 312 y 419 healthy controls as well as a panel of 257 celiac families. Genotyping for the -336A/G CD209 promoter polymorphism was performed using a TaqMan 5' allelic discrimination assay. HLA-DQ was determined by hybridization with allele specific probes. RESULTS: Initially, the case-control and familial studies did not find any association of the -336 A/G CD209 genetic variant with CD susceptibility. However, the stratification by HLA-DQ2 did reveal a significant association of CD209 promoter polymorphism in the HLA-DQ2 (-) group (carrier A vs GG in DQ2 (-) vs DQ2 (+) patients (P = 0.026, OR = 3.71). CONCLUSION: The -336G CD209 allele seems to be involved in CD susceptibility in HLA-DQ2 (-) patients. Our results might suggest a possible role of pathogens in the onset of a minor group of CD patients.
Asunto(s)
Enfermedad Celíaca/genética , Moléculas de Adhesión Celular/genética , Antígenos HLA-DQ/genética , Lectinas Tipo C/genética , Regiones Promotoras Genéticas/genética , Receptores de Superficie Celular/genética , Alelos , Estudios de Casos y Controles , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/etnología , Enfermedad Celíaca/fisiopatología , Moléculas de Adhesión Celular/fisiología , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/fisiología , Humanos , Lectinas Tipo C/fisiología , Masculino , Polimorfismo Genético , Regiones Promotoras Genéticas/fisiología , Receptores de Superficie Celular/fisiología , Índice de Severidad de la Enfermedad , España/epidemiología , España/etnología , Población Blanca/genéticaRESUMEN
We have studied the effect of ectopic overexpression of a ras gene on the expression of the other two members of the ras gene family. We obtained NIH3T3 cell lines stably transfected with inducible H-ras and N-ras oncogenes. The expression of these genes is driven by a glucocorticoid-responsive promoter and the addition of dexamethasone resulted in a dramatic induction (10-20-fold) of H- or N-ras mRNA, peaking 4 h after hormone addition. The induction of the expression of ras oncogenes resulted in a transformed phenotype. In quiescent NIH3T3 cells transfected with inducible H-ras oncogenes, the induction of H-Ras was followed 12 h later by a 3-fold increase in the mRNA expression of endogenous K-ras and N-ras. Similarly, in NIH3T3 transfected with inducible N-ras oncogene, the induction of N-ras was followed by an increase in the expression of endogenous K- and H-ras genes. Interestingly, the effect was not limited to the mutated N-ras, as a similar result was obtained in cells transfected with N-ras proto-oncogene. The induction of ras genes expression was not linked to cell cycle progression as it was reproduced in cells arrested in S-phase by pretreatment with hydroxyurea. These results suggest the presence of a positive cross-regulation in the expression among the members of the Ras family. This effect could play a role in Ras-mediated carcinogenesis.
Asunto(s)
Regulación de la Expresión Génica , Genes ras , Transcripción Genética/efectos de los fármacos , Células 3T3 , Animales , Dexametasona/farmacología , Fibroblastos , Regulación de la Expresión Génica/efectos de los fármacos , Homeostasis , Cinética , Ratones , Proteína Oncogénica p21(ras)/biosíntesis , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/biosíntesis , TransfecciónRESUMEN
The susceptibility to develop celiac disease (CD) seems to be primarily associated to a particular HLA-DQ alpha/beta heterodimer encoded by the DQA1*0501 and DQB1*0201 alleles, in cis position on the DR3-DQ2 haplotype or in trans position by DR5-DQ7/DR7-DQ2 heterozygotes. However, exceptional patients exist who are neither DR3 nor DR5/DR7, particularly among Southern European populations. We therefore examined the DRB1, DQA1, and DQB1 alleles of 13 Spanish CD patients who were serologically typed to be neither DR3 nor DR5/DR7. Five patients were found to carry the DQA1*0501 and DQB1*0201 alleles either in cis or in trans position, three of them had previously been serologically mistyped. However, two of these patients carried DQA1*0501 and DQB1*0201 on haplotypes other than DR3 or DR5 in combination with DR7. One of the latter patients carried an unusual DR4-DQ2 haplotype, while another had an unusual DR8-DQ2 haplotype. Four of the remaining eight patients carried DR4-DQ8 haplotypes. Taken together, our findings provide further evidence that the DQ alpha/beta heterodimer encoded by the DQA1*0501 and the DQB1*0201 alleles confers the primary HLA-associated susceptibility to develop CD. However, our studies also corroborate that a second (and "weaker") HLA-associated CD susceptibility gene may be present on some DR4-carrying haplotypes.
Asunto(s)
Enfermedad Celíaca/inmunología , Antígenos HLA-DQ/análisis , Antígenos HLA-DR/análisis , Adolescente , Adulto , Niño , Susceptibilidad a Enfermedades , Femenino , Haplotipos , Humanos , Inmunofenotipificación , Masculino , Sondas de Oligonucleótidos , EspañaRESUMEN
The possibility that genetic susceptibility to celiac disease (CD) might be influenced by tumor necrosis factor (TNF) genes polymorphism has repeatedly been put forward. To date, this has only been investigated in case-control studies and results have been contradictory. In order to avoid any possible ethnic mismatching between patients and controls, we have approached this problem studying 71 celiac families, establishing the parental haplotypes and comparing CD versus control haplotypes (the so-called AFBAC or affected family-based controls). We used DNA-based methods to screen for HLA-DRB1, -DQA1, and -DQB1 alleles, TNFalpha promoter polymorphims and TNFa and b microsatellites. The guanine-to-adenine polymorphism at position -308 of the TNFalpha gene promoter region was found associated with CD as the TNF-308A allele appeared significantly increased in frequency in CD haplotypes, and this was shown to be independent of the association between CD and the DRB1*0301,DQA1*0501,DQB1*0201 alleles. Our results indicate that at least another gene, in addition to the known association of CD with HLA class II, has a susceptibility role in this disease. This should be either TNFalpha or another polymorphic gene in the telomeric end of the HLA class III region.
Asunto(s)
Enfermedad Celíaca/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Factor de Necrosis Tumoral alfa/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/genética , Cadenas alfa de HLA-DQ , Cadenas beta de HLA-DQ , Antígenos HLA-DR/genética , Antígeno HLA-DR3/genética , Cadenas HLA-DRB1 , Haplotipos , Humanos , España/epidemiologíaRESUMEN
Jejunal biopsy specimens from nine Spanish children with gluten-sensitive enteropathy were studied with morphometric and immunohistochemical techniques in three stages of the diseases: the first biopsy was taken for diagnosis, when the child had a gluten-containing diet, the second after gluten withdrawal, and the third biopsy after gluten-provocation. The findings were compared with those in 10 healthy adults. The villous:crypt ratio and the length of the surface epithelium per stretched millimetre muscularis mucosae were decreased, whereas the number of interepithelial lymphocytes per millimetre surface epithelium was increased when the child had a gluten-containing diet. Although these parameters improved after withdrawal of gluten for at least seven months, they never reached the values of the healthy control group. With the indirect immunoperoxidase technique it was shown that the numbers of IgA-, IgG-, and IgM-containing cells, expressed per "mucosal tissue unit" of 4 micrometer thick and 1 mm wide, were significantly increased during the active phases of the disease. This increase was most striking for the IgM-containing cells. The most sensitive parameters for the histological diagnosis of gluten-sensitive enteropathy are the villous:crypt ratio or the length of the surface epithelium per millimetre muscularis mucosae, the number of interepithelial lymphocytes per millimetre surface epithelium, and the number of IgM-containing cells per millimetre muscularis mucosae.
Asunto(s)
Enfermedad Celíaca/patología , Yeyuno/patología , Enfermedad Celíaca/inmunología , Preescolar , Epitelio/patología , Femenino , Humanos , Inmunoglobulinas/análisis , Lactante , Yeyuno/inmunología , Masculino , Persona de Mediana EdadRESUMEN
AIM: Analyze the results of a paediatric intestinal transplantation (IT) program in Spain. PATIENTS: During an 5-year period, 18 children were included as candidates for IT. The causes for intestinal failure (IF) were short bowel syndrome (n=13), motility disorders (n=3), and congenital epithelial disorders (n=2). Nine children were admitted for a combined liver-small bowel transplant (LSBT), seven for an isolated intestinal transplantation (IIT) and two for a multivisceral transplantation (MVT). In three of the candidates for IIT the indication had to be changed to LSBT because of progression of the liver damage. RESULTS: Eight candidates are on the waiting list: four for LSBT, two for IIT, and two for MVT. Four children died before transplantation. All were children under 1 year and candidates for LSBT. One child died during an attempted MVT. Five children underwent transplantation. Grafts were IIT in two and LSBT in three. Of these children, two are on a normal diet (respective follow-up times: 40 and 18 months), two died, both with functioning liver and intestinal grafts (hemorrage after liver biopsy and lymphoproliferative disease), and one developed an untreatable rejection that lead to loss of the intestinal graft; currently, she is on the waiting list for LSBT. CONCLUSIONS: The morbidity and mortality of IT are high, but it is the only possible treatment for children in IF who cannot be adequately managed with parenteral nutrition. A severe problem is the the scarcity of suitable donors for the very low weight children who are candidates for LSBT.
Asunto(s)
Intestinos/trasplante , Síndrome del Intestino Corto/cirugía , Trasplante Homólogo , Adolescente , Niño , Preescolar , Humanos , Lactante , Estudios Retrospectivos , España , Resultado del Tratamiento , Listas de EsperaRESUMEN
Dysphagia and gastroesophageal reflux (GER) probably caused by structural disorganization of the esophagus occur frequently after repair of tracheoesophageal fistula (TEF), and the extent to which they may improve beyond childhood is not known. The aim of the present study is to assess by combined ambulatory 24-hour manometry and pH-metry the esophageal peristaltic activity and acid clearing capacity in adolescents and adults who had been operated on for TEF at birth. Twenty-two patients, aged 17.1 +/- 4.5 years (mean +/- SD), were examined with combined three-channel manometry and two-channel pH-metry followed by endoscopy and biopsy. Although they considered themselves healthy, on careful interrogation, 16 (72%) were found to have dysphagia, 13 (59%) had heartburn, 10 (45%) had foreign body impaction, and 7 (31%) had chronic respiratory tract disease. GER was detected in 12 (54%) patients (5 with histological esophagitis), 10 of whom had a pattern of prolonged nocturnal episodes with very slow clearance. All patients had diminished contractile activity with low-amplitude and short-duration waves that decreased from 0.53 +/- 0.35 waves per minute to 0.28 +/- 0.2 waves per minute during sleep. Propulsive activity was uniformly disorganized, with peristaltic sequences being few (less than 50% overall) and incomplete (above 80%). Finally, the acid-clearing capacity was nil; the proportions of ineffective sequences were above 90% for all periods considered, including sleep and mealtimes. The motor behavior of nonrefluxing and refluxing patients was identical despite the differences in esophageal acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)