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61.
Berbari NF Lewis JS Bishop GA Askwith CC Mykytyn K 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(11):4242-4246
Primary cilia are ubiquitous cellular appendages that provide important yet not well understood sensory and signaling functions. Ciliary dysfunction underlies numerous human genetic disorders. However, the precise defects in cilia function and the basis of disease pathophysiology remain unclear. Here, we report that the proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localization of G protein-coupled receptors to primary cilia on central neurons. We demonstrate a lack of ciliary localization of somatostatin receptor type 3 (Sstr3) and melanin-concentrating hormone receptor 1 (Mchr1) in neurons from mice lacking the Bbs2 or Bbs4 gene. Because Mchr1 is involved in the regulation of feeding behavior and BBS is associated with hyperphagia-induced obesity, our results suggest that altered signaling caused by mislocalization of ciliary signaling proteins underlies the BBS phenotypes. Our results also provide a potential molecular mechanism to link cilia defects with obesity. 相似文献
62.
Katritsis DG Pantos I Efstathopoulos EP Tzanalaridou E Korovesis S Kourlaba G Paxinos G Voridis E 《Coronary artery disease》2008,19(4):265-270
OBJECTIVE: This study aimed at comparing three-dimensional (3-D) reconstruction with two-dimensional coronary angiograms with respect to anatomical parameters that might affect plaque formation and rupture. METHODS: Sixty patients with stable left anterior descending (LAD) lesions and 60 patients with an anteroseptal myocardial infarction and recanalized LAD were studied. RESULTS: Conventional angiography significantly underestimated the distance of the stenosis from the ostium of the LAD, 29.4+/-14.5 versus 35.3+/-18.5 mm, P<0.001. Vessel curvature at the site of the lesion was overestimated by conventional angiography compared with 3-D reconstruction, 147.6+/-30.6 degrees versus 162.3+/-11.2 degrees , P<0.001, as was axial bending of the LAD owing to ventricular contraction (17.8+/-7.78 degrees vs. 8.9+/-8.9 degrees , P<0.001). No agreement was observed between two-dimensional and 3-D analysis for either curvature on lesion or axial bending assessment, with intraclass correlation coefficient values 0.155 (-0.009, 0.315) and -0.022 (-0.183, 0.174), respectively. No significant agreement was found between the two methods in the detection of on-stenosis bifurcations (1.7%, kappa=0.086, P=0.349). CONCLUSION: Conventional coronary angiography cannot provide accurate estimates of anatomical parameters, such as distance of a coronary stenosis from the ostium of the vessel, coronary artery curvature at the site of stenosis, axial deformity and bending because of ventricular contraction, and classification of bifurcations. Reconstruction of the coronary tree in 3-D space is necessary for such estimations. 相似文献
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Georgia R. Gore‐Langton Matthew Cairns Yves Daniel Compaor Issaka Sagara Irene Kuepfer Issaka Zongo Mariken M. de Wit Amadou Barry Modibo Diarra Amadou Tapily Samba Coumare Ismail Thera Frederic Nikiema R. Serge Yerbanga Rosemonde M. Guissou Halidou Tinto Alassane Dicko Daniel Chandramohan Brian Greenwood Jean Bosco Ouedraogo 《Tropical medicine & international health : TM & IH》2020,25(6):740-750
65.
Jos Dreesen Aspasia Destouni Georgia Kourlaba Birte Degn Wulf Christensen Mette Filipa Carvalho Celine Moutou Sioban Sengupta Seema Dhanjal Pamela Renwick Steven Davies Emmanouel Kanavakis Gary Harton Joanne Traeger-Synodinos 《European journal of human genetics : EJHG》2014,22(8):1012-1018
Preimplantation genetic diagnosis (PGD) for monogenic disorders currently involves polymerase chain reaction (PCR)-based methods, which must be robust, sensitive and highly accurate, precluding misdiagnosis. Twelve adverse misdiagnoses reported to the ESHRE PGD-Consortium are likely an underestimate. This retrospective study, involving six PGD centres, assessed the validity of PCR-based PGD through reanalysis of untransferred embryos from monogenic-PGD cycles. Data were collected on the genotype concordance at PGD and follow-up from 940 untransferred embryos, including details on the parameters of PGD cycles: category of monogenic disease, embryo morphology, embryo biopsy and genotype assay strategy. To determine the validity of PCR-based PGD, the sensitivity (Se), specificity (Sp) and diagnostic accuracy were calculated. Stratified analyses were also conducted to assess the influence of the parameters above on the validity of PCR-based PGD. The analysis of overall data showed that 93.7% of embryos had been correctly classified at the time of PGD, with Se of 99.2% and Sp of 80.9%. The stratified analyses found that diagnostic accuracy is statistically significantly higher when PGD is performed on two cells versus one cell (P=0.001). Se was significantly higher when multiplex protocols versus singleplex protocols were applied (P=0.005), as well as for PGD applied on cells from good compared with poor morphology embryos (P=0.032). Morphology, however, did not affect diagnostic accuracy. Multiplex PCR-based methods on one cell, are as robust as those on two cells regarding false negative rate, which is the most important criteria for clinical PGD applications. Overall, this study demonstrates the validity, robustness and high diagnostic value of PCR-based PGD. 相似文献
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Lito Flouda Ageliki Pandazi Charalampos Papageorgiou Despoina Perrea Eleni Krepi Georgia Kostopanagiotou 《Archives of Medical Science》2013,9(1):105-111
Introduction
Unconscious processing of words during general anaesthesia has been suggested. We used the process dissociation procedure (PDP) to test memory performance during sevoflurane and propofol anaesthesia in relation to hypnotic depth.Material and methods
One hundred participants anaesthetised for elective surgery (50 with propofol and 50 with sevoflurane) and 50 non-anaesthetized listened to a list of words. The bispectral index (BIS) of the anaesthetised patients was recorded. Within 36 h after word presentation, memory was assessed using a word stem completion task, based on Buchner''s model applied on the PDP.Results
There was evidence of memory for words presented during light (BIS 61-80) (p = 0.001) and adequate (BIS 41-60) (p = 0.008) but not deep anaesthesia (BIS 21-40) (p = 0.09). The PDP showed a significant implicit but not explicit memory contribution (mean total explicit memory scores: 0.04 ±0.07 in all BIS categories; mean implicit memory scores: 0.01 ±0.04, 0.1 ±0.08, and 0.05 ±0.09 at BIS = 21-40, 41-60, and 61-80, respectively). There was a statistically significant difference between the mean implicit memory score (I) of the propofol and sevoflurane group in the BIS category 41-60 in general (p = 0.016), and after incision (IA.I.) (p = 0.005) in particular, with propofol depressing I more than sevoflurane in both cases. Memory performance of nonanaesthetized participants was better, with a higher contribution of explicit and a comparable contribution of implicit memory.Conclusions
During general anaesthesia, implicit memory persists even in adequate hypnotic states. Sevoflurane affects the implicit memory of adequately anaesthetised subjects less than propofol. 相似文献70.
H. Krichen Y. Gorgi T. Dhaouadi Y. Mecheri I. Sfar R. Bardi M.M. Bacha E. Abderrahim S. Jendoubi-Ayed K. Ayed T. Ben Abdallah 《Transplantation proceedings》2013,45(10):3472-3477
BackgroundAcute and chronic rejections remain an important cause of graft loss after renal transplantation. Currently, activation of innate immune responses through Toll-like receptors (TLRs) is suspected to be implied in the loss of the transplant tolerance.ObjectivesWe investigated functional single nucleotide polymorphisms (SNPs) of TLR4 and its coreceptor CD14 in kidney transplantation and looked for any potential role in acute rejection (AR) and chronic allograft nephropathy (CAN) and impact on graft survival.Patients and MethodsTLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 209 kidney transplant recipients (KTRs) including 132 treated with mycophenolate mofetil (MMF+). AR occurred in 59 patients and 24 were identified as having CAN by biopsy and scored according to the Banff criteria.ResultsThere were no significant associations between TLR4 and CD14 genotypes and alleles and the occurrence of both AR episodes and CAN. Moreover, TLR4 and CD14 SNPs did not seem to influence kidney graft survival. Analysis according to human leukocyte antigen (HLA) compatibility status, positivity of anti-HLA antibodies, and immunosuppression by MMF confirmed the absence of correlation of the investigated SNPs with the graft outcome. In addition, incidence of post-transplantation infections, including cytomegalovirus (CMV) infections, was not influenced by both TLR4 and CD14 SNPs.ConclusionThese results suggest that TLR4 (Asp299Gly) and CD14 (C/T -159) functional SNPs do not play a major role in AR, CAN, and kidney graft survival. Therefore, intragraft monitoring of TLR4/CD14 genes expression by messenger RNA (mRNA) would provide clarity on the exact role of these receptors in graft injuries. 相似文献