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排序方式: 共有6485条查询结果,搜索用时 15 毫秒
101.
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Joao B. Augusto Nicolas Johner Dipen Shah Sabrina Nordin Kristopher Knott Stefania Rosmini Clement Lau Mashael Alfarih Rebecca Hughes Andreas Seraphim Ravi Vijapurapu Anish Bhuva Linda Lin Natalia Ojrzyńska Tarekegn Geberhiwot Gabriella Captur Uma Ramaswami Richard P. Steeds Mehdi Namdar 《Molecular genetics and metabolism》2021,132(2):S17-S18
103.
Per Anderson Natalia Aptsiauri Francisco Ruiz-Cabello Federico Garrido 《Cellular & molecular immunology》2021,18(3):556
T cell-mediated immune therapies have emerged as a promising treatment modality in different malignancies including colorectal cancer (CRC). However, only a fraction of patients currently respond to treatment. Understanding the lack of responses and finding biomarkers with predictive value is of great importance. There is evidence that CRC is a heterogeneous disease and several classification systems have been proposed that are based on genomic instability, immune cell infiltration, stromal content and molecular subtypes of gene expression. Human leukocyte antigen class I (HLA-I) plays a pivotal role in presenting processed antigens to T lymphocytes, including tumour antigens. These molecules are frequently lost in different types of cancers, including CRC, resulting in tumour immune escape from cytotoxic T lymphocytes during the natural history of cancer development. The aim of this review is to (i) summarize the prevalence and molecular mechanisms behind HLA-I loss in CRC, (ii) discuss HLA-I expression/loss in the context of the newly identified CRC molecular subtypes, (iii) analyze the HLA-I phenotypes of CRC metastases disseminated via blood or the lymphatic system, (iv) discuss strategies to recover/circumvent HLA-I expression/loss and finally (v) review the role of HLA class II (HLA-II) in CRC prognosis. 相似文献
104.
Andrea Sánchez Paulina Bustos Paula Honorato Carlos F. Burgos Natalia Barriga Cinthia E. Jannes Katia Sáez Rodrigo Alonso Sylvia Asenjo Claudia Radojkovic 《Journal of clinical lipidology》2021,15(2):366-374.e1
BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH. 相似文献
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Miriam Schmidts Valeska Frank Tobias Eisenberger Saeed al Turki Albane A. Bizet Dinu Antony Suzanne Rix Christian Decker Nadine Bachmann Martin Bald Tobias Vinke Burkhard Toenshoff Natalia Di Donato Theresa Neuhann Jane L. Hartley Eamonn R. Maher Radovan Bogdanovi Amira Peco‐Anti Christoph Mache Matthew E. Hurles Ivana Joksi Marija Gu‐eki Jelena Dobricic Mirjana Brankovic‐Magic Hanno J. Bolz Gregory J. Pazour Philip L. Beales Peter J. Scambler Sophie Saunier Hannah M. Mitchison Carsten Bergmann 《Human mutation》2013,34(5):714-724
Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy. 相似文献
108.
Delena Caagbay Friyan Turel Fatakia Hans Peter Dietz Camille Raynes-Greenow Natalia Martinho Kirsten I. Black 《Revista brasileira de fisioterapia (S?o Carlos (S?o Paulo, Brazil))》2021,25(2):214-220
BackgroundPelvic floor muscle function has been shown to be inversely associated with pelvic organ prolapse in Western women, however differences have been documented between ethnic groups.ObjectiveTo determine if pelvic floor muscle strength and thickness and hiatal area are associated with pelvic organ prolapse in Nepali women.MethodsThis cross-sectional study included non-pregnant Nepali women ≥18 years attending an outpatient gynecology clinic in Kathmandu, Nepal. A clinical examination included the pelvic organ prolapse quantification (POP-Q)- system examination and Modified Oxford Scale. Puborectalis muscle thickness and hiatal area were assessed using 3D/4D translabial ultrasound. Statistical analysis included Pearson's correlation and multiple regression (p < 0.05).ResultsOf the 123 women; 14 (11%) had POP-Q stage 0 prolapse, 29 (24%) stage I, 69 (56%) stage II, 8 (7%) stage III, and 3 (2%) stage IV. Mean ± SD Modified Oxford Scale was 3.37 ± 0.48 and muscle thickness was 1.14 ± 0.21 cm, hiatal area at rest was 14.67 ± 3.11 cm2 and on contraction was 11.29 ± 2.51 cm2. No associations were found between pelvic floor muscle strength or thickness and POP-Q stages 0–IV. There was a positive correlation found between hiatal area at rest and pelvic organ prolapse stage (r = 0.34, p < 0.001)and hiatal area on contraction and prolapse stage (r = 0.30, p < 0.001) and a negative correlation between pelvic floor muscle strength and hiatal area on contraction (r = ?0.36, p < 0.001).ConclusionIn contrast to previous findings, pelvic floor muscle strength and thickness are not associated with pelvic organ prolapse in this sample of Nepali women. It is important to consider these findings when developing pelvic organ prolapse treatment and management strategies in this population. 相似文献
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110.
Johannes Kirchner Michael Broll Phillip Müller Natalia Pomjanski Stepfan Biesterfeld Dieter Liermann Ralph Kickuth 《Diagnostic and interventional radiology (Ankara, Turkey)》2015,21(2):128-133