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AIM: Chronic hepatitis C viral (HCV) infections often result in ineffective CD8 T-cell responses due to functional exhaustion of HCV-specific T cells. However, how persisting HCV impacts CD8 T-cell effector functions remains largely unknown. The aim of this study is to examine the effect of the infectious dose and the presence of HCV core gene. METHODS: We compared responses of intrahepatic CD8 T cells during infection of wild-type or HCV core transgenic (Tg) mice with various infectious doses of HCV-NS3-expressing recombinant adenovirus (Ad-HCV-NS3). RESULTS: Using major histocompatibility complex class I tetramer and intracellular interferon (IFN)-γ staining method to track HCV-NS3-specific CD8 T cells, we found that a significant expansion of HCV-NS3-specific CD8 T cells was restricted to a very narrow dosage range. IFN-γ production by intrahepatic CD8 T cells in HCV core Tg mice was suppressed as compared with wild-type mice. Higher levels of expression of regulatory molecules, Tim-3 and PD-1, by intrahepatic CD8 T cells and PD-L1 by intrahepatic antigen-presenting cells were observed in HCV core Tg mice following Ad-HCV-NS3 infection, and the expression increased dependent on infectious dose. Furthermore, we found a significant inverse correlation between the percentages of IFN-γ-producing cells and expression of regulatory molecules in antigen-specific intrahepatic CD8 T cells. CONCLUSION: High infectious dose and the presence of HCV core gene were strongly involved in ineffective CD8 T-cell responses. We consider that HCV core Tg mouse infected with high infectious dose of Ad-HCV-NS3 is useful as a chronic infection model in the development of immunotherapy for chronic hepatitis C.
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An 80-year-old man presented to our clinic with a chief complaint about pain and stiffness in the right knee. His history was significant for osteomyelitis of the right femur 64 years ago. Examination revealed a range of motion from 30 degrees hyperextension to 0 degrees extension. A rotating-hinge total knee arthroplasty was performed. Four years later, the patient ambulates painlessly with 1 cane. He has no extensor lag, and his range of motion is 0 degrees to 15 degrees.
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Artroplastia de Reemplazo de Rodilla/métodos , Deformidades Adquiridas de la Articulación/cirugía , Articulación de la Rodilla , Prótesis de la Rodilla , Anciano de 80 o más Años , Fémur , Humanos , Deformidades Adquiridas de la Articulación/etiología , Deformidades Adquiridas de la Articulación/fisiopatología , Masculino , Osteomielitis/complicaciones , Diseño de Prótesis , Rango del Movimiento Articular , Factores de TiempoRESUMEN
In vivo three-dimensional patellar tracking under weightbearing conditions was investigated with the principal reference axes of the femur in the coronal and axial planes, using a biplanar image-matching technique. Three-dimensional knee models of eight healthy volunteers were constructed using computed tomography scanning. Projection images of the models were fitted onto anteroposterior and lateral radiographs of the knees at hyperextension and at every 15 degrees from 0 degrees to 120 degrees flexion. Knee motion then was reconstructed on a computer. Patellar tracking during knee flexion was described simply with a medial jerk shift of 8 mm in early flexion until 30 degrees and a linear tracking with minimal mediolateral translation. The linear tracking portion was located laterally 5 mm from the mediolateral center of the femoral condyles. On average, the direction of this linear tracking was almost perpendicular to the distal condylar line in the coronal plane and perpendicular to the posterior condylar axis in the axial plane. These results help improve the understanding of patellofemoral kinematics and provide useful information for the design and positioning of the prostheses used in total knee arthroplasty.
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Fémur/fisiología , Articulación de la Rodilla/fisiología , Rótula/fisiología , Adulto , Fémur/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Rótula/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Soporte de PesoRESUMEN
To determine the chromosomal positions of expressed rice genes, we have performed an expressed sequence tag (EST) mapping project by polymerase chain reaction-based yeast artificial chromosome (YAC) screening. Specific primers designed from 6713 unique EST sequences derived from 19 cDNA libraries were screened on 4387 YAC clones and used for map construction in combination with genetic analysis. Here, we describe the establishment of a comprehensive YAC-based rice transcript map that contains 6591 EST sites and covers 80.8% of the rice genome. Chromosomes 1, 2, and 3 have relatively high EST densities, approximately twice those of chromosomes 11 and 12, and contain 41% of the total EST sites on the map. Most of the EST-dense regions are distributed on the distal regions of each chromosome arm. Genomic regions flanking the centromeres for most of the chromosomes have lower EST density. Recombination frequency in these regions is suppressed significantly. Our EST mapping also shows that 40% of the assigned ESTs occupy only approximately 21% of the entire genome. The rice transcript map has been a valuable resource for genetic study, gene isolation, and genome sequencing at the Rice Genome Research Program and should become an important tool for comparative analysis of chromosome structure and evolution among the cereals.