Factors Contributing to Troponin Exchange in Myofibrils and in Solution

The troponin complex in a muscle fiber can be replaced with exogenous troponin by using a gentle exchange procedure in which the actin–tropomyosin complex is never devoid of a full complement of troponin (Brenner et al. (1999) Biophys J 77: 2677–2691). The mechanism of this exchange process and the factors that influence this exchange are poorly understood. In this study, the exchange process has now been examined in myofibrils and in solution. In myofibrils under rigor conditions, troponin exchange occurred preferentially in the region of overlap between actin and myosin when the free Ca²⁺ concentration was low. At higher concentrations of Ca²⁺, the exchange occurred uniformly along the actin. Ca²⁺ also accelerated troponin exchange in solution but the effect of S1 could not be confirmed in solution experiments. The rate of exchange in solution was insensitive to moderate changes in pH or ionic strength. Increasing the temperature resulted in a two-fold increase in rate with each 10°C increase in temperature. A sequential two step model of troponin binding to actin–tropomyosin could simulate the observed association and dissociation transients. In the absence of Ca²⁺ or rigor S1, the following rate constants could describe the binding process: k ₁ = 7.12 M^–1s^–1, k _–1 = 0.65 s^–1, k ₂ = 0.07 s^–1, k _–2 = 0.0014 s^–1. The slow rate of detachment of troponin from actin (k _–2) limits the rate of exchange in solution and most likely contributes to the slow rate of exchange in fibers.     

Monte Carlo dose verification for intensity-modulated arc therapy

Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan. Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-Ill computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.     

人脑颞叶组织中类固醇5a－还原酶同功酶活性分布研究

本文采用酶放射分析法对新鲜人脑颞叶组织中５ａ－还原酶同功酶的活性分布进行研究。结果显示：（１）在颞叶脑组织中，５ａ－还原酶１和５ａ－还原酶２主要分布在灰质，其酶活性（５ａ－还原酶１，３３．６±４．５ｐｍｏｌ·ｈ_（－１）／ｍｇ蛋白，ｎ＝１２；５ａ－还原酶２，１３．８±２．９ｐｍｏｌ·ｈ_（－１）／ｍｇ蛋白，ｎ＝１１）明显高于分布在白质中的酶活性（５ａ－还原酶１，１４．７±２．０ｐｍｏｌ·ｈ_（－１）／ｍｇ蛋白，ｎ＝１２，Ｐ＜０．００１；５ａ－还原酶２，５．２±０．９ｐｍｏｌ·ｈ_（－１）／ｍｇ蛋白，ｎ＝１１，Ｐ＜０，０１）；（２）在灰质中，５ａ－还原酶活性主要来自于５ａ－还原酶１，其酶活性（３４．９±２．５ｐｍｏｌ·ｈ_（－１）／ｍｇ蛋白，ｎ＝３２）明显高于５ａ－还原酶２（１５．０±２．３ｐｍｏｌ·ｒ_（－１）／ｍｇ蛋白，ｎ＝１８，（Ｐ＜０．００１）；（３）５ａ－还原酶１和５ａ－还原酶２的活性在男女性之间差异不显著，且与年龄无相关关系。     

横向电场作用下外周神经兴奋特性的实验研究

传统的外周神经电缆方程只能描述纵向电场刺激下外周神经兴奋,实验发现在脉冲磁场诱导的横向电场作用下也可使神经兴奋,从而揭示出需要进一步对感应电场兴奋外周神经的机理进行研究。本文研究了横向电场作用下外周神经的兴奋特性,以在体的人体正中神经为例研究了横向电场作用下外周神经兴奋点的位置、刺激阈值、及刺激阈值与纤维半径的关系,以离体的蟾蜍坐骨神经为例研究了刺激阈值与作用时间的关系。实验结果验证了改进的电缆方程的有效性。实验研究成果有助于磁刺激技术的进一步发展与应用。     

Effect of interferon on the structural organization of rat thymus

Changes in the thymus of male Wistar rats were studied under a light microscope at various times after intranasal administration of α-interferon. The relative mass of the organ, the cortex volume, the total number of cells, the number of small and medium lymphocytes, and the number of mitoses decrease 14 days after interferon administration. At the same time, the number of macrophages, neutrophils, mature plasmacytes, eosinophils, and erythrocytes increases, and mast cells appear. Thus, α-interferon probably suppresses the formation of T cells, facilitates allergization of the organism, and increases the permeability of the vascular endothelium. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 609–612, December, 1994     

脑缺血后TLR4作用与小胶质细胞的激活

脑缺血性损伤早期小胶质细胞即被激活。激活的小胶质细胞既有细胞毒性又有神经营养作用。小胶质细胞行使免疫功能的信号转导受体之一是TLR4（toll-like receptor 4）。TLR4在脑内主要表达在小胶质细胞，是一种模式识别受体（pattern recognition receptor，PRR）, 识别一些外源性和内源性的配体。最近的研究表明，TLR4信号通路在脑缺血再灌注损伤中起重要作用。TLR4通过激活小胶质细胞，大量表达炎症因子，加重脑缺血性损伤。     

Effect of hindlimb unloading on resting intracellular calcium in intrafusal fibers and ramp-and-hold stretches evoked responsiveness of soleus muscle spindles in conscious rats

The present study was to investigate and evaluate the dynamic changes of calcium homeostasis of soleus muscle spindle for the exploration of the potential mechanisms of muscle spindle degeneration induced by hindlimb unloading. We systematically observed the changes in immunoreactivity of calbindin D28K (CaBP-D28K), intracellular resting calcium in intrafusal fibers of soleus muscle spindle, and the responsiveness of muscle spindles to ramp-and-hold stretches after short- and long-term (3, 7, 14 d) hindlimb unloading. The immunoreactivity of CaBP-D28K started to decrease after 7-d hindlimb unloading, while its decrease was obviously different compared with the control group 14 d following the hindlimb unloading. The resting calcium concentration was increased significantly at 3 d, and reached the peak level 14 d after the hindlimb unloading. The responsiveness of muscle spindles, assessed by investigating Index3-L₂, Index3-L₃, and Index5, to ramp-and-hold stretches started to decrease during the period of 7-d hindlimb unloading. All Indexs, in particular Index3-L₃ and Index5, were significantly decreased at 14 d after the hindlimb unloading. The data suggest the disturbance of calcium homeostasis in intrafusal fibers during the exposure to hindlimb unloading might gradually influence the structure and function of muscle spindles.     

Interferon-gamma is an autocrine mediator for dendritic cell maturation

Maturation of dendritic cells (DC) is critical for efficient antigen presentation and initiation of an immune response. Interferon-gamma (IFN-gamma) is an important Th1 cytokine. In this study, we investigated the role of IFN-gamma in DC maturation using either IFN-gamma receptor deficient- or IFN-gamma overexpression-models. We showed that immature DC generated in vitro from bone marrow (BM) progenitor cells produced low level of IFN-gamma. After LPS stimulation, DC produced more IFN-gamma, and IFN-gamma productions were at comparable levels among C57BL/6 mice-derived DC (C57BL/6 DC), wild-type 129 mice-derived DC (129 DC) and IFN-gamma receptor deficient 129 mice-derived DC (IFN-gammaR-/-DC). We found that IFN-gammaR-/-DC exhibited decreased expression of CD54, CD86, reduced capacity to secrete IL-1beta and IL-12p70, and impaired capacity to stimulate alloreactive T cells and to drive Th1 differentiation. Transfection of IFN-gamma gene into DC promoted DC to express higher CD40, CD54, CD80, CD86, CCR7 and I-Ab, secrete more IL-1beta and IL-12p70, and more potently activate both CD4 and CD8 T cells. These data suggest that IFN-gamma signaling pathway is important for the maturation of DC in an autocrine fashion.