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71.
Bing Yue Kartik M. Varadarajan Songtao Ai Tingting Tang Harry E. Rubash Guoan Li 《Knee surgery, sports traumatology, arthroscopy》2011,19(1):80-88
The goal of this study was to characterize the geometry of the distal femur and proximal tibia in the Chinese population.
Three-dimensional models of twenty female and twenty male knees were constructed using CT images. The morphologic measurements
of the distal femur included mediolateral (ML) and anteroposterior dimension of medial and lateral condyles (MAP, LAP), femoral
aspect ratio (ML/LAP), medial and lateral condylar width, intercondylar notch width, notch width index (NWI), and trochlear
groove orientation. The sagittal profiles of the medial and lateral femoral condyles and tibial plateaus were also characterized.
The results showed that the size of the distal femur of the females was significantly smaller than that of the males. Furthermore,
when normalized by LAP, the females had a significantly narrower distal femur (ML), and a shorter MAP compared to the males.
In the sagittal plane, the radius of the lateral distal circle of the femur was significantly smaller than that of the medial
condyle in both genders. There were no significant gender differences in the proximal tibial geometry. The data of the present
study may enable suitable modification of total knee prosthesis sizing/geometry for Asia-Pacific patients. 相似文献
72.
Manuchehry A Agusala K Montevecchi M Kadish A Passman R 《Pacing and clinical electrophysiology : PACE》2011,34(5):571-576
Introduction: Data on the mechanisms of sudden cardiac death are limited and may be biased by delays in rhythm recording and selection bias in survivors. As a result, the relative contributions of monomorphic ventricular tachycardia (VT) (cycle length [CL] > 260 ms), monomorphic fast VT (FVT) (CL ≤ 260 ms), and polymorphic VT (PMVT)/ventricular fibrillation (VF) have not been well characterized nor compared in patients with and without prior arrhythmic events. Methods: A retrospective cohort study of implantable cardioverter‐defibrillator (ICD) recipients with primary or secondary implant indications was used to evaluate intracardiac electrograms (EGMs) for the first spontaneous VT/VF resulting in appropriate ICD therapy. EGMs were categorized into VT, FVT, and PMVT/VF based on CL and morphologic criteria. Results: Of 616 implants, 145 patients (58 [40%] primary indications) received appropriate ICD therapy for VT/VF over mean follow‐up of 3.8 ± 3.2 years. Primary implants had more diabetes (28% vs 12%; P = 0.02) and less antiarrhythmic use (15% vs 33%; P = 0.02). In those patients with spontaneous arrhythmia, PMVT/VF occurred in 20.7% of primary versus 21.8% of secondary implants, FVT in 19.0% versus 21.8%, and VT in 60.3% versus 56.4%, respectively (P = 0.88). Spontaneous VT CL was similar regardless of implant indication (284 ± 56 [primary] vs 286 ± 67 ms [secondary]; P = 0.92). Conclusions: Monomorphic VT is the most common cause of appropriate ICD therapy regardless of implant indication. These results provide insight into the mechanisms of sudden cardiac death and have implications for the use of interventions designed to limit ICD shocks. (PACE 2011; 34:571–576) 相似文献
73.
74.
Ezrin mediates growth and survival in Ewing’s sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway 总被引:5,自引:0,他引:5
Krishnan K Bruce B Hewitt S Thomas D Khanna C Helman LJ 《Clinical & experimental metastasis》2006,23(3-4):227-236
Recent reports on the role of the membrane-cytoskeleton linker protein ezrin in sarcomas showed an effect on the formation of metastases, dependent on the level of ezrin expression. In this study, we explore the role of ezrin in Ewing’s sarcoma, a frequently fatal mesenchymal neoplasm of children and young adults. Through both immunohistochemistry and Western immunoblot studies we find ubiquitous, high-level expression of ezrin in Ewing’s sarcoma. In contrast to the observations in osteosarcoma and rhabdomyosarcoma, we demonstrate that inhibition of ezrin-mediated signal transduction, through the expression of a non-phosphorylatable T567A mutant, slows primary growth of Ewing’s sarcoma cells in vitro. This reduction in growth is a result of increased apoptosis in the mutant expressing cells. We further show that expression of this mutant reduces the ability of Ewing’s sarcoma cells to form experimental metastases in vivo. Molecular examination reveals that the action of ezrin in Ewing’s sarcoma is dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase. These results, therefore, demonstrate that, in Ewing’s sarcoma, the biology of ezrin is distinct from that described in other sarcomas. This study further validates ezrin as a potential therapeutic target. 相似文献
75.
Kartik R Rao ChV Trivedi SP Pushpangadan P Reddy GD 《Indian journal of pharmacology》2010,42(6):370-375
Objective:
The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis.Materials and Methods:
The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl4), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl4, treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups.Results:
The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl4 -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group.Conclusion:
These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl4-induced two-stage hepatocarcinogenesis. 相似文献76.
Qin Y Xu J Aysola K Oprea G Reddy A Matthews R Okoli J Cantor A Grizzle WE Partridge EE Reddy ES Landen C Rao VN 《American journal of cancer research》2012,2(5):540-548
Mutation in the BRCA1 gene is associated with increased risk for hereditary breast and ovarian cancers. In sporadic ovarian tumors, BRCA1 dysfunction is thought to be common. BRCA1 is a nuclear-cytoplasm shuttling protein. Our group has previously reported that BRCA1 proteins, unlike K109R and cancer-predisposing mutant C61G BRCA1 proteins, bind the sole SUMO E2-conjugating enzyme Ubc9. In this study, we examined the result of altered Ubc9 binding and knockdown on the sub-cellular localization and growth inhibitory function of BRCA1 proteins in ovarian cancer cells. Using live imaging of YFP, RFP-tagged BRCA1 and BRCA1a proteins, our results show enhanced cytoplasmic localization of K109R and C61G mutant BRCA1 proteins in ES-2, NIHOVCAR3 and UWB 1.289 ovarian cancer cells. Down-regulation of Ubc9 in ovarian cancer cells using Ubc9 siRNA resulted in cytoplasmic localization of BRCA1 and BRCA1a proteins. These mutant BRCA1a proteins were impaired in their capacity to inhibit growth of ES-2 ovarian cancer cells. Several ovarian cancer cells, including a BRCA1-null ovarian cancer cell line, showed higher levels of expression of Ubc9. This is the first study demonstrating the physiological link between loss of Ubc9 binding and loss of growth suppression of disease-associated mutant BRCA1a proteins in ovarian cancer cells. BRCA1, by turning off or on Ubc9 binding, regulates growth of ovarian cancers. 相似文献
77.
Pekkan K Whited B Kanter K Sharma S de Zelicourt D Sundareswaran K Frakes D Rossignac J Yoganathan AP 《Medical & biological engineering & computing》2008,46(11):1139-1152
The first version of an anatomy editing/surgical planning tool (SURGEM) targeting anatomical complexity and patient-specific
computational fluid dynamics (CFD) analysis is presented. Novel three-dimensional (3D) shape editing concepts and human–shape
interaction technologies have been integrated to facilitate interactive surgical morphology alterations, grid generation and
CFD analysis. In order to implement “manual hemodynamic optimization” at the surgery planning phase for patients with congenital
heart defects, these tools are applied to design and evaluate possible modifications of patient-specific anatomies. In this
context, anatomies involve complex geometric topologies and tortuous 3D blood flow pathways with multiple inlets and outlets.
These tools make it possible to freely deform the lumen surface and to bend and position baffles through real-time, direct
manipulation of the 3D models with both hands, thus eliminating the tedious and time-consuming phase of entering the desired
geometry using traditional computer-aided design (CAD) systems. The 3D models of the modified anatomies are seamlessly exported
and meshed for patient-specific CFD analysis. Free-formed anatomical modifications are quantified using an in-house skeletization
based cross-sectional geometry analysis tool. Hemodynamic performance of the systematically modified anatomies is compared
with the original anatomy using CFD. CFD results showed the relative importance of the various surgically created features
such as pouch size, vena cave to pulmonary artery (PA) flare and PA stenosis. An interactive surgical-patch size estimator
is also introduced. The combined design/analysis cycle time is used for comparing and optimizing surgical plans and improvements
are tabulated. The reduced cost of patient-specific shape design and analysis process, made it possible to envision large
clinical studies to assess the validity of predictive patient-specific CFD simulations. In this paper, model anatomical design
studies are performed on a total of eight different complex patient specific anatomies. Using SURGEM, more than 30 new anatomical
designs (or candidate configurations) are created, and the corresponding user times presented. CFD performances for eight
of these candidate configurations are also presented.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
78.
Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade 总被引:2,自引:0,他引:2
Graham DM Wong KY Shapiro P Frederick C Pattabiraman K Berson DM 《Journal of neurophysiology》2008,99(5):2522-2532
Intrinsically photosensitive retinal ganglion cells (ipRGCs) are photoreceptors of the mammalian eye that drive pupillary responses, synchronization of circadian rhythms, and other reflexive responses to daylight. Melanopsin is the ipRGC photopigment, but the signaling cascade through which this invertebrate-like opsin triggers the photocurrent in these cells is unknown. Here, using patch-clamp recordings from dissociated ipRGCs in culture, we show that a membrane-associated phosphoinositide cascade lies at the heart of the ipRGC phototransduction mechanism, similar to the cascade in rhabdomeric photoreceptors of invertebrate eyes. When ipRGCs were illuminated, melanopsin activated a G protein of the G(q/11) class, stimulating the effector enzyme phospholipase C. The presence of these signaling components in ipRGCs was confirmed by single-cell RT-PCR and immunofluorescence. The photoresponse was fully functional in excised inside-out patches of ipRGC membrane, indicating that all core signaling components are within or tightly coupled to the plasma membrane. The striking similarity of phototransduction in ipRGCs and invertebrate rhabdomeric photoreceptors reinforces the emerging view that these cells have a common evolutionary origin. 相似文献
79.
Kombo DC Mazurov A Tallapragada K Hammond PS Chewning J Hauser TA Vasquez-Valdivieso M Yohannes D Talley TT Taylor P Caldwell WS 《European journal of medicinal chemistry》2011,46(11):5625-5635
AChBPs isolated from Lymnaea stagnalis (Ls), Aplysia californica (Ac) and Bulinus truncatus (Bt) have been extensively used as structural prototypes to understand the molecular mechanisms that underlie ligand-interactions with nAChRs [1]. Here, we describe docking studies on interactions of benzylidene anabaseine analogs with AChBPs and α7 nAChR. Results reveal that docking of these compounds using Glide software accurately reproduces experimentally-observed binding modes of DMXBA and of its active metabolite, in the binding pocket of Ac. In addition to the well-known nicotinic pharmacophore (positive charge, hydrogen-bond acceptor, and hydrophobic aromatic groups), a hydrogen-bond donor feature contributes to binding of these compounds to Ac, Bt, and the α7 nAChR. This is consistent with benzylidene anabaseine analogs with OH and NH2 functional groups showing the highest binding affinity of these congeners, and the position of the ligand shown in previous X-ray crystallographic studies of ligand-Ac complexes. In the predicted ligand-Ls complex, by contrast, the ligand OH group acts as hydrogen-bond acceptor. We have applied our structural findings to optimizing the design of novel spirodiazepine and spiroimidazoline quinuclidine series. Binding and functional studies revealed that these hydrogen-bond donor containing compounds exhibit improved affinity and selectivity for the α7 nAChR subtype and demonstrate partial agonism. The gain in affinity is also due to conformational restriction, tighter hydrophobic enclosures, and stronger cation-π interactions. The use of AChBPs structure as a surrogate to predict binding affinity to α7 nAChR has also been investigated. On the whole, we found that molecular docking into Ls binding site generally scores better than when a α7 homology model, Bt or Ac crystal structure is used. 相似文献
80.
Pappu KS Morey M Nern A Spitzweck B Dickson BJ Zipursky SL 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(18):7571-7576
The formation of neuronal connections requires the precise guidance of developing axons toward their targets. In the Drosophila visual system, photoreceptor neurons (R cells) project from the eye into the brain. These cells are grouped into some 750 clusters comprised of eight photoreceptors or R cells each. R cells fall into three classes: R1 to R6, R7, and R8. Posterior R8 cells are the first to project axons into the brain. How these axons select a specific pathway is not known. Here, we used a microarray-based approach to identify genes expressed in R8 neurons as they extend into the brain. We found that Roundabout-3 (Robo3), an axon-guidance receptor, is expressed specifically and transiently in R8 growth cones. In wild-type animals, posterior-most R8 axons extend along a border of glial cells demarcated by the expression of Slit, the secreted ligand of Robo3. In contrast, robo3 mutant R8 axons extend across this border and fasciculate inappropriately with other axon tracts. We demonstrate that either Robo1 or Robo2 rescues the robo3 mutant phenotype when each is knocked into the endogenous robo3 locus separately, indicating that R8 does not require a function unique to the Robo3 paralog. However, persistent expression of Robo3 in R8 disrupts the layer-specific targeting of R8 growth cones. Thus, the transient cell-specific expression of Robo3 plays a crucial role in establishing neural circuits in the Drosophila visual system by selectively regulating pathway choice for posterior-most R8 growth cones. 相似文献