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L. M. Borrego M. J. Arroz P. Videira C. Martins H. Guimarães G. Nunes A. L. Papoila H. Trindade 《Clinical and experimental allergy》2009,39(8):1160-1169
Background Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms. Objectives This study was designed to assess and compare the immunological status during the first 2 years in steroid‐naïve young children with three episodes of physician‐confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age‐matched healthy controls (n=30). Methods Peripheral blood CD4+CD25+ and CD4+CD25high T cells and their cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN‐γ, TGF‐β and IL‐10), CTLA‐4 and Foxp3 mRNA expression were evaluated (real‐time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12‐myristate 13‐acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day). Results Flow cytometry results showed a significant reduction in the absolute number of CD4+CD25high and the absolute and percentage numbers of CD4+CD25+CTLA‐4+ in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4+CD25+ (P=0.01) and CD4+CD25high (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA‐4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA‐4 (P=0.03) and IFN‐γ (P=0.04) expression was diminished in wheezy children compared with healthy children. High‐risk children had lower expression of IFN‐γ (P=0.03) compared with low‐risk and healthy children and lower expression of CTLA‐4 (P=0.01) compared with healthy children. Conclusions Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life. 相似文献
73.
A Novel Point Variant in NTRK3, R645C, Suggests a Role of this Gene in the Pathogenesis of Hirschsprung Disease 总被引:1,自引:0,他引:1
R. M. Fernández A. Sánchez-Mejías M. D. Mena M. Ruiz-Ferrer M. López-Alonso G. Antiñolo S. Borrego 《Annals of human genetics》2009,73(1):19-25
Hirschsprung disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the myenteric and submucosal plexuses due to a defect in the migration process of neural crest neuroblasts. Manifestation of the disease has been linked to the dysfunction of two principal signalling pathways involved in the enteric nervous system (ENS) formation: the RET-GDNF and the EDN3-EDNRB receptor systems. However, the NTF3/NTRK3 signalling pathway plays an essential role in the development of the ENS suggesting a potential role for those genes in the pathogenesis of HSCR. We have sought to evaluate the candidature of the NTRK3 gene, which encodes the TrkC receptor, as a susceptibility gene for Hirschsprung disease. Using dHPLC technology we have screened the NTRK3 coding region in 143 Spanish HSCR patients. A total of four previously described polymorphisms and 12 novel sequence variants were detected. Of note, the novel R645C mutation was detected in 2 affected siblings of a HSCR family also carrying a RET splicing mutation. Using bioinformatics tools we observed that the presence of an additional cysteine residue might implicate structural alterations in the mutated protein. We propose haploinsufficiency as the most probable mechanism for the NTRK3 R645C mutation. NTRK3 and RET mutations in this family only appear together in the HSCR patients, suggesting that they per se are necessary but not sufficient to produce the phenotype. In addition, it is quite probable that the contribution of other still unidentified modifier genes, may be responsible for the different phenotypes (length of aganglionosis) in the two affected members. 相似文献
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van Engen Catherine E Ofman Rob Dijkstra Inge ME Schackmann Martin J Wanders Ronald JA Kemp Stephan 《Tijdschrift voor kindergeneeskunde》2013,81(1):10-10
Tijdschrift voor Kindergeneeskunde - 相似文献
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Suk Yun Kang MD PhD Toshiaki Wasaka PhD Ejaz A. Shamim MD Sungyoung Auh PhD Yoshino Ueki MD PhD Grisel J. Lopez MD Tetsuo Kida PhD Seung‐Hyun Jin PhD Nguyet Dang ME Mark Hallett MD 《Movement disorders》2010,25(13):2148-2155
The sequence effect (SE) in Parkinson's disease (PD) is progressive slowing of sequential movements. It is a feature of bradykinesia, but is separate from a general slowness without deterioration over time. It is commonly seen in PD, but its physiology is unclear. We measured general slowness and the SE separately with a computer‐based, modified Purdue pegboard in 11 patients with advanced PD. We conducted a placebo‐controlled, four‐way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation (rTMS) could improve general slowness or the SE. We also examined the correlation between the SE and clinical fatigue. Levodopa alone and rTMS alone improved general slowness, but rTMS showed no additive effect on levodopa. Levodopa alone, rTMS alone, and their combination did not alleviate the SE. There was no correlation between the SE and fatigue. This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE. Additionally, the SE is not a component of clinical fatigue. Further work is needed to establish the physiology and clinical relevance of the SE. © 2010 Movement Disorder Society. 相似文献
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ME Penny 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(S383):114-120
It has been suggested that proliferation of enterobacteriaceae and/or anaerobes in the duodenum of some children with acute diarrhoea determines whether the episode becomes persistent. A review of published studies and the comparison of cultures of duodenal aspirates from Peruvian children with acute and persistent diarrhoea and diarrhoea-free children did not support this hypothesis. Although many children had enterobacteriaceae and/or anaerobes cultured there was no correlation with clinical and nutritional outcome. Age, nutritional status, the environment and the aetiology of the episode were determinants of the duodenal microflora independent of diarrhoea. Culture of the duodenal aspirates did not increase the yield of enteropathogens which were isolated more frequently from stools than from the duodenum. Despite the presence of a single strain or serotype of enterobacteriaceae suggesting that these bacteria were colonizing the duodenum, we were unable to demonstrate any adherence mechanisms in the majority of them. Two often bacteria with no other evidence of virulence caused diarrhoea in the RITARD rabbit model. 相似文献
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