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71.
Maternal uniparental isodisomy (iUPD) of chromosome 4 in a subject with mild intellectual disability and speech delay 下载免费PDF全文
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Linda Pilgaard Joachim Høg Mortensen Michael Henriksen Pia Olesen Preben Sørensen Rene Laursen Mogens Vyberg Ralf Agger Vladimir Zachar Torben Moos Meg Duroux 《Brain pathology (Zurich, Switzerland)》2014,24(4):360-370
Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto‐1 (CR‐1) has a key regulatory role in embryogenesis, while in adult tissue re‐expression of CR‐1 has been correlated to malignant progression in solid cancers of non‐neuronal origin. As CR‐1 expression has yet to be described in cerebral cancer and CR‐1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR‐1 in the context of expression in GBM. The study was performed using enzyme‐linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low‐grade glioma patients. Within the patient cohort, we found high CR‐1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR‐1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR‐1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target. 相似文献
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Gabriela E Jones Pia Ostergaard Anthony T Moore Fiona C Connell Denise Williams Oliver Quarrell Angela F Brady Isabel Spier Filiz Hazan Oana Moldovan Dagmar Wieczorek Barbara Mikat Florence Petit Christine Coubes Robert A Saul Glen Brice Kristiana Gordon Steve Jeffery Peter S Mortimer Pradeep C Vasudevan Sahar Mansour 《European journal of human genetics : EJHG》2014,22(7):881-887
Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing. 相似文献
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Sofia Asioli Maria Pia Foschini Riccardo Masetti Vincenzo Eusebi 《Endocrine pathology》2014,25(2):141-150
In the skin and breast, endocrine tumors are composed of a heterogeneous mixture of endocrine and exocrine cells. The definition of “pure” endocrine carcinomas is a matter for debate, and as a consequence, there is lack of uniform diagnostic criteria. There are no significant clinical differences in either overall or disease-free survival between matched neoplasms with endocrine and without endocrine differentiation nor between the degree of endocrine differentiation and tumor size, stage, or prevalence of vascular invasion for both sites (skin and breast). Here, endocrine tumors of the skin and breast are grouped respectively into three categories that include most of the neuroendocrine tumors of the skin and breast as seen in routine practice. It was felt that the number of different types of neuroendocrine tumors is so conspicuous that it is impossible to organize them in an orderly classification. It has been proposed therefore, for practical diagnostic routine purposes, to arrange these neoplasms into a working formulation. The latter includes heterogeneous lesions respectively of the skin and breast within the same group that have clinical features in common. 相似文献
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Stefano?CarloneEmail author Bruno?Balbi Michela?Bezzi Marco?Brunori Stefano?Calabro Maria?Pia?Foschino Barbaro Claudio?Micheletto Salvatore?Privitera Roberto?Torchio Pietro?Schino Andrea?Vianello 《Multidisciplinary respiratory medicine》2014,9(1):63
This article deals with the prevalence and the possible reasons of COPD underestimation in the population and gives suggestions on how to overcome the obstacles and make the correct diagnosis in order to provide the patients with the appropriate therapy. COPD is diagnosed in later or very advanced stages. In Italy the rate of COPD under-diagnosis ranges between 25 and 50% and, as a consequence, the patient does not consult his doctor until the symptoms have worsened, mainly due to exacerbations. A missed diagnosis influences the timing of therapeutic intervention, thus contributing to the evolution into more severe stages of the illness. An incisive intervention to limit under-diagnosis cannot act only in remittance (passive diagnosis), but must be the promoter for a series of preventive actions: primary, secondary and rehabilitative. To reduce under-diagnosis, some actions need to be taken, such as screening programs for smokers subjects, use of questionnaires aimed to qualify and monitor the disease severity, spirometry, early diagnosis. There is a consensus regarding diagnoses based on screening of at-risk subjects and symptoms, rather than screening of the general population. In practice, all individuals over 40 years of age with risk factors should make a spirometry test. Screening actions on a national scale can be the following: compilation of questionnaires in waiting rooms of doctor’s offices or performing simple maneuvers to evaluate the expiratory force at pharmacies. It is now widely recognized that COPD is a complex syndrome with several pulmonary and extrapulmonary components; as a result, the airway obstruction as assessed by FEV1 by itself does not adequately describe the complexity of the disease and FEV1 cannot be used alone for the optimal diagnosis, assessment, and management of the disease. The identification and subsequent grouping of key elements of the COPD syndrome into clinically meaningful and useful subgroups (phenotypes) can guide therapy more effectively. In conclusion, we firmly believe that an early and correct diagnosis can influence positively the progress of the disease (lowering the lung function impairment), decrease the risk of exacerbations, relieve symptoms and increase the patients’ quality of life leading also to a decrease in costs associated to the exacerbations and hospitalization of the patient. 相似文献
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The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together 总被引:2,自引:0,他引:2
Pathare GR Nagy I Bohn S Unverdorben P Hubert A Körner R Nickell S Lasker K Sali A Tamura T Nishioka T Förster F Baumeister W Bracher A 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(1):149-154
Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1?? resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP. 相似文献