角质形成细胞生长因子(KGF)在喉粘膜良性、癌前及恶性病变中的mRNA水平分析

利用原位杂交的方法检测KGFmRNA在正常喉粘膜上皮（N）、慢性非特异性炎症（IF）、不典型增生（DYS）及鳞癌（SCC）中的转录水平,探讨KGF在喉粘膜良性及恶性病变中的分布和可能的作用。结果表明,KGFmRNA不仅在间质中的成纤维细胞中表达,少量的炎细胞及血管内皮细胞中亦表达,而且从N、IF、DYS到SCC、KGFmRNA转录水平逐渐增强;上皮细胞及肿瘤性上皮细胞不表达KGFmRNA,KGFmRNA在分化差的SCC周围间质中表达较分化好的SCC周围间质增多。结论：KGF在上皮与间充质细胞的交互作用中发挥着重要的作用,对维持喉粘膜正常结构、代谢及喉癌的发生发展具有重要意义。     

A model for the neuronal implementation of selective visual attention based on temporal correlation among neurons

We propose a model for the neuronal implementation of selective visual attention based on temporal correlation among groups of neurons. Neurons in primary visual cortex respond to visual stimuli with a Poisson distributed spike train with an appropriate, stimulus-dependent mean firing rate. The spike trains of neurons whose receptive fields donot overlap with the focus of attention are distributed according to homogeneous (time-independent) Poisson process with no correlation between action potentials of different neurons. In contrast, spike trains of neurons with receptive fields within the focus of attention are distributed according to non-homogeneous (time-dependent) Poisson processes. Since the short-term average spike rates of all neurons with receptive fields in the focus of attention covary, correlations between these spike trains are introduced which are detected by inhibitory interneurons in V4. These cells, modeled as modified integrate-and-fire neurons, function as coincidence detectors and suppress the response of V4 cells associated with non-attended visual stimuli. The model reproduces quantitatively experimental data obtained in cortical area V4 of monkey by Moran and Desimone (1985).     

Sensitivity of damage predictions to tissue level yield properties and apparent loading conditions

High-resolution finite element models of trabecular bone failure could be used to augment current techniques for measuring damage in trabecular bone. However, the sensitivity of such models to the assumed tissue yield properties and apparent loading conditions is unknown. The goal of this study was to assess the sensitivity of the amount and mode (tension vs. compression) of tissue level yielding in trabecular bone to these factors. Linear elastic, high-resolution finite element models of nine bovine tibial trabecular bone specimens were used to calculate the fraction of the total tissue volume that exceeded each criterion for apparent level loading to the reported elastic limit in both on-axis and transverse compression and tension, and in shear. Four candidate yield criteria were studied, based on values suggested in the literature. Both the amount and the failure mode of yielded tissue were sensitive to the magnitudes of the tissue yield strains, the degree of tension-compression asymmetry of the yield criterion, and the applied apparent loads. The amount of yielded tissue was most sensitive to the orientation of the applied apparent loading, with the most tissue yielding for loading along the principal trabecular orientation and the least for loading perpendicular to it, regardless of the assumed tissue level yield criterion. Small changes in the magnitudes and the degree of asymmetry of the tissue yield criterion resulted in much larger changes in the amount of yielded tissue in the model. The results indicate that damage predictions based on high-resolution finite element models are highly sensitive to the assumed tissue yield properties. As such, good estimates of these values are needed before high-resolution finite element models can be applied to the study of trabecular bone damage. Regardless of the assumed tissue yield properties, the amount and type of damage that occurs in trabecular bone depends on the relative orientations of the applied apparent loads to the trabecular architecture, and this parameter should be controlled for both experimental and computational damage studies.     

The effect of holding time on nanoindentation measurements of creep in bone

Viscoelasticity may affect both the elastic and fracture characteristics of bone. Nanoindentation can be used to measure the creep behavior of bone by fitting the depth vs. time data at constant load to rheological models. However, the creep data may be influenced by latent effects arising during the loading phase of indentation. As such, the loading protocol, particularly the holding time, may affect the measured creep time constants. To characterize the effect of holding time on the measures, four cortical bone samples were prepared from four bovine femora and subjected to nanoindentation to measure the creep behavior. The creep time constants were found by fitting the indentation depth vs. time curve to three different rheological models: the standard linear solid, Burgers model, and a two-dashpot Kelvin model. All three models provided good fits to the data, which were relatively insensitive to the initial parameter estimates. The calculated creep time constants increased monotonically with increasing holding time for all three models. However, the relative differences between measurements within a single osteon, within a single sample, and between samples were maintained for creep holding times over 16s. Hence, while the creep time constants measured by nanoindentation with hold times up to 30s may not provide accurate property measurements, comparisons between samples are valid if all are assessed at the same holding time. Considering the long-term viscosity of bone tissue, Burgers model provided the best performance in terms of stability and goodness of fit, and is recommended for future studies.     

Shear strength and toughness of trabecular bone are more sensitive to density than damage

Microdamage occurs in trabecular bone under normal loading, which impairs the mechanical properties. Architectural degradation associated with osteoporosis increases damage susceptibility, resulting in a cumulative negative effect on the mechanical properties. Treatments for osteoporosis could be targeted toward increased bone mineral density, improved architecture, or repair and prevention of microdamage. Delineating the relative roles of damage and architectural degradation on trabecular bone strength will provide insight into the most beneficial targets. In this study, damage was induced in bovine trabecular bone samples by axial compression, and the effects on the mechanical properties in shear were assessed. The damaged shear modulus, shear yield stress, ultimate shear stress, and energy to failure all depended on induced damage and decreased as the architecture became more rod-like. The changes in ultimate shear strength and toughness were proportional to the decrease in shear modulus, consistent with an effective decrease in the cross-section of trabeculae based on cellular solid analysis. For typical ranges of bone volume fraction in human bone, the strength and toughness were much more sensitive to decreased volume fraction than to induced mechanical damage. While ultimately repairing or avoiding damage to the bone structure and increasing bone density both improve mechanical properties, increasing bone density is the more important contributor to bone strength.     

Bone ingrowth into a porous coated implant predicted by a mechano-regulatory tissue differentiation algorithm

Bone ingrowth into a porous surface is one of the primary methods for fixation of orthopaedic implants. Improved understanding of bone formation and fixation of these devices should improve their performance and longevity. In this study predictions of bone ingrowth into an implant porous coating were investigated using mechano-reculatory models. The mechano-regulatory tissue differentiation algorithm proposed by Lacroix et al., and a modified version that enforces a tissue differentiation pathway by transitioning from differentiation to bone adaptation were investigated. The modified algorithm resulted in nearly the same behavior as the original algorithm when applied to a fracture-healing model. The algorithms were further compared using micromechanical finite element model of a beaded porous scaffold. Predictions of bone and fibrous tissue formation were compared between the two algorithms and to clinically observed phenomena. Under loading conditions corresponding to a press-fit hip stem, the modified algorithm predicted bone ingrowth into approximately 25% of the pore space, which is similar to that reported in experimental studies, while the original algorithm was unstable. When micromotion at the bone-implant interface was simulated, 20 mum of transverse displacement resulted in soft tissue formation at the bone-implant interface and minimal bone ingrowth. In contrast, 10 and 5 mum of micromotion resulted in bone filling 40% of the pore space and a stable interface, again consistent with clinical and experimental observations.