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71.
L. Echevarria K. Benistan A. Toussaint O. Dubourg A.A. Hagege D. Eladari F. Jabbour C. Beldjord P. De Mazancourt D.P. Germain 《Clinical genetics》2016,89(1):44-54
Fabry disease (FD) is an X‐linked genetic disorder caused by the deficient activity of lysosomal α‐galactosidase (α‐Gal). While males are usually severely affected, clinical presentation in female patients may be more variable ranging from asymptomatic to, occasionally, as severely affected as male patients. The aim of this study was to evaluate the existence of skewed X‐chromosome inactivation (XCI) in females with FD, its concordance between tissues, and its contribution to the phenotype. Fifty‐six females with FD were enrolled. Clinical and biological work‐up included two global scores [Mainz Severity Score Index (MSSI) and DS3], cardiac magnetic resonance imaging, measured glomerular filtration rate, and measurement of α‐Gal activity. XCI was analyzed in four tissues using DNA methylation studies. Skewed XCI was found in 29% of the study population. A correlation was found in XCI patterns between blood and the other analyzed tissues although some punctual variability was detected. Significant differences in residual α‐Gal levels, severity scores, progression of cardiomyopathy and deterioration of kidney function, depending on the direction and degree of skewing of XCI were evidenced. XCI significantly impacts the phenotype and natural history of FD in females. 相似文献
72.
Kelly M. Morgan Jada G. Hamilton Heather Symecko Daniella Kamara Colby Jenkins Jenny Lester Kelsey Spielman Lydia E. Pace Camila Gabriel Jeffrey D. Levin Prince Rainier Tejada Anthony Braswell Vanessa Marcell Temima Wildman Bryan Devolder Robin Camhi Baum Jeremy N. Block Yuri Fesko Kenneth Offit 《Genetics in medicine》2022,24(3):564-575
PurposeThis study aimed to evaluate uptake and follow-up using internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs).MethodsAcross 4 cities in the United States, from December 2017 to March 2020, individuals aged ≥25 years with ≥1 Ashkenazi Jewish grandparent were offered enrollment. Participants consented and enrolled online with chatbot and video education, underwent BRCA1/2 AJPV GT, and chose to receive results from their primary care provider (PCP) or study staff. Surveys were conducted at baseline, at 12 weeks, and annually for 5 years.ResultsA total of 5193 participants enrolled and 4109 (79.1%) were tested (median age = 54, female = 77.1%). Upon enrollment, 35.1% of participants selected a PCP to disclose results, and 40.5% of PCPs agreed. Of those tested, 138 (3.4%) were AJPV heterozygotes of whom 21 (15.2%) had no significant family history of cancer, whereas 86 (62.3%) had a known familial pathogenic variant. At 12 weeks, 85.5% of participants with AJPVs planned increased cancer screening; only 3.7% with negative results and a significant family history reported further testing.ConclusionAlthough continued follow-up is needed, internet-enabled outreach can expand access to targeted GT using a medical model. Observed challenges for population genetic screening efforts include recruitment barriers, improving PCP engagement, and increasing uptake of additional testing when indicated. 相似文献
73.
Axenfeld–Rieger syndrome (ARS) is a rare autosomal dominant disorder, which encompasses a range of congential malformations affecting the anterior segment of the eye. ARS shows genetic heterogeneity and mutations of the two genes, PITX2 and FOXC1, are known to be associated with the pathogenesis. There are several excellent reviews dealing with the complexity of the phenotype and genotype of ARS. In this study, we will attempt to give a brief review of the clinical features and the relevant diagnostic approaches, together with a detailed review of published PITX2 and FOXC1 mutations. 相似文献
74.
Patton Daniella Ghosh Adarsh Farkas Amy Sotardi Susan Francavilla Michael Venkatakrishna Shyam Bose Saurav Ouyang Minhui Huang Hao Davidson Richard Sze Raymond Nguyen Jie 《Journal of digital imaging》2023,36(4):1419-1430
Journal of Digital Imaging - Measurement of angles on foot radiographs is an important step in the evaluation of malalignment. The objective is to develop a CNN model to measure angles on... 相似文献
75.
Julien Favresse Constant Gillot Jean-Louis Bayart Clara David Germain Simon Loris Wauthier Mélanie Closset Jean-Michel Dogné Jonathan Douxfils 《Journal of medical virology》2023,95(1):e28164
Evidence about the long-term persistence of the booster-mediated immunity against Omicron is mandatory for pandemic management and deployment of vaccination strategies. A total of 155 healthcare professionals (104 COVID-19 naive and 51 with a history of SARS-CoV-2 infection) received a homologous BNT162b2 booster. Binding antibodies against the spike protein and neutralizing antibodies against Omicron were measured at several time points before and up to 6 months after the booster. Geometric mean titers of measured antibodies were correlated to vaccine efficacy (VE) against symptomatic disease. Compared to the highest response, a significant 10.2- and 11.5-fold decrease in neutralizing titers was observed after 6 months in participants with and without history of SARS-CoV-2 infection. A corresponding 2.5- and 2.9-fold decrease in binding antibodies was observed. The estimated T1/2 of neutralizing antibodies in participants with and without history of SARS-CoV-2 infection was 42 (95% confidence interval [CI]: 25–137) and 36 days (95% CI: 25–65). Estimated T1/2 were longer for binding antibodies: 168 (95% CI: 116–303) and 139 days (95% CI: 113–180), respectively. Both binding and neutralizing antibodies were strongly correlated to VE (r = 0.83 and 0.89). However, binding and neutralizing antibodies were modestly correlated, and a high proportion of subjects (36.7%) with high binding antibody titers (i.e., >8434 BAU/ml) did not have neutralizing activity. A considerable decay of the humoral response was observed 6 months after the booster, and was strongly correlated with VE. Our study also shows that commercial assays available in clinical laboratories might require adaptation to better predict neutralization in the Omicron era. 相似文献
76.
Reconstructed human cornea produced in vitro by tissue engineering. 总被引:13,自引:0,他引:13
L Germain F A Auger E Grandbois R Guignard M Giasson H Boisjoly S L Guérin 《Pathobiology》1999,67(3):140-147
The aim of the present study was to produce a reconstructed human cornea in vitro by tissue engineering and to characterize the expression of integrins and basement membrane proteins in this reconstructed cornea. Epithelial cells and fibroblasts were isolated from human corneas (limbus or centre) and cultured on plastic substrates in vitro. Reconstructed human corneas were obtained by culturing epithelial cells on collagen gels containing fibroblasts. Histological (Masson's trichrome staining) and immunohistological (laminin, type VII collagen, fibronectin as well as beta1, alpha3, alpha4, alpha5, and alpha6 integrin subunits) studies were performed. Human corneal epithelial cells from the limbus yielded colonies of small fast-growing cells when cultured on plastic substrates. They could be subcultured for several passages in contrast to central corneal cells. In reconstructed cornea, the epithelium had 4-5 cell layers by the third day of culture; basal cells were cuboidal. The basement membrane components were already detected after 3 days of culture. Integrin stainings, except for the alpha4 integrin, were also positive after 3 days. They were mostly detected at the epithelium-stroma junction. Such in vitro tissue-engineered human cornea, which shows appropriate histology and expression of basement membrane components and integrins, provides tools for further physiological, toxicological and pharmacological studies as well as being an attractive model for gene expression studies. 相似文献
77.
Chronic exposure to Helicobacter pylori impairs dendritic cell function and inhibits Th1 development 总被引:2,自引:0,他引:2
Mitchell P Germain C Fiori PL Khamri W Foster GR Ghosh S Lechler RI Bamford KB Lombardi G 《Infection and immunity》2007,75(2):810-819
Helicobacter pylori causes chronic gastric infection that affects the majority of the world's population. Despite generating an inflammatory response, the immune system usually fails to clear the infection. Since dendritic cells (DCs) play a pivotal role in shaping the immune response, we investigated the effects of H. pylori on DC function. We have demonstrated that H. pylori increased the expression of activation markers on DCs while upregulating the inhibitory B7 family molecule, PD-L1. Functionally, H. pylori-treated DCs resulted in the production of interleukin-10 (IL-10) and IL-23 but not of alpha interferon (IFN-alpha). While very little or no IL-12 was produced to H. pylori alone, simultaneous ligation of CD40 on DCs induced IL-12 release. We also demonstrated that DCs treated with H. pylori-induced IFN-gamma production by allogeneic naive T cells. However, stimulation of DCs with H. pylori for an extended period of time impaired their ability to produce cytokines after CD40 ligation and limited their ability to promote IFN-gamma release, suggesting that the DCs had become exhausted by the prolonged stimulation. The effect of chronic infection with H. pylori on DC function was further investigated by focusing on DC development. Demonstrating that monocytes differentiated into DCs in the presence of H. pylori exhibited an exhausted phenotype with an impaired ability to produce IL-12 and a downregulation of CD1a. Our results raise the possibility that in chronic H. pylori infection DCs become exhausted after prolonged antigen exposure leading to suboptimal Th1 development. This effect may contribute to persistence of H. pylori infection. 相似文献
78.
Fertility outcome after ectopic pregnancy and use of an intrauterine device at the time of the index ectopic pregnancy 总被引:3,自引:0,他引:3
Bernoux A Job-Spira N Germain E Coste J Bouyer J 《Human reproduction (Oxford, England)》2000,15(5):1173-1177
Fertility after ectopic pregnancy (EP) was investigated in a non-selected population taking into account intrauterine device (IUD) use at the time of the EP. Between January 1992 and June 1996, 647 women listed in the EP register of Auvergne (France) were followed up. The analysis included only the 328 women who were seeking to become pregnant: 23 women using IUD at the time of the index EP (IUD users) and 305 IUD non-users. Among IUD users, there was no recurrence of EP, and the 1 year cumulative rate was 87% [95% confidence interval (CI): 73-100%] for intrauterine pregnancies and 86% (95% CI: 72-100%) for deliveries. Among IUD non-users, the 2 year cumulative rate for recurrence of EP was 28% (95% CI: 17-39%), and the 1 year cumulative rates were 60% (95% CI: 53-66%) for intrauterine pregnancies and 44% (95% CI: 38-56%) for deliveries. The adjusted intrauterine pregnancy rate of IUD users was not significantly different from that of IUD non-users. However, IUD non-users had more miscarriages, so their delivery rate was lower. 相似文献
79.
Nair Lopes Bárbara Sousa Daniella Vieira Fernanda Milanezi & Fernando Schmitt 《Histopathology》2009,55(5):594-599
Aims: To evaluate the relationship between microvessel density assessed by endoglin expression and the molecular subtypes of human invasive breast carcinomas and whether there is evidence to indicate that angiogenesis could be a putative target for therapy in specific subsets of breast cancer.
Methods and results: We studied a series of 161 breast carcinomas, but information was available on only 142 tumours. We correlated endoglin expression with distinct breast carcinoma subgroups classified according to immunohistochemical profiling. Additionally, we compared it with other biomarkers for the aggressive basal-like subset and with available histopathological data. Although the basal-like subtype has higher microvessel density, there are no significant differences with the other molecular subtypes of breast cancer.
Conclusions: This study found no significant differences in tumour vascularity in different molecular subtypes of breast cancer. 相似文献
Methods and results: We studied a series of 161 breast carcinomas, but information was available on only 142 tumours. We correlated endoglin expression with distinct breast carcinoma subgroups classified according to immunohistochemical profiling. Additionally, we compared it with other biomarkers for the aggressive basal-like subset and with available histopathological data. Although the basal-like subtype has higher microvessel density, there are no significant differences with the other molecular subtypes of breast cancer.
Conclusions: This study found no significant differences in tumour vascularity in different molecular subtypes of breast cancer. 相似文献