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1.
Interaction of interleukin 2 (IL2) with its high affinity membrane receptor complex (IL2R) is sufficient to induce proliferation of T lymphocytes. However, the biochemical mechanisms by which IL2 induces this process remain unresolved. The IL2R complex consists of at least two distinct polypeptides that bind IL2, a 75-kDa intermediate affinity subunit (IL2R beta) and a 55-kDa low affinity subunit (IL2R alpha). As indicated by Western blotting with anti-phosphotyrosine-specific antibodies and confirmed by phosphoamino acid analysis, we now demonstrate that interaction of the T cell growth factor interleukin 2 (IL2) with its high affinity receptor on IL2-sensitive human peripheral blood lymphoblasts induces tyrosine phosphorylation of proteins of 92, 80, 78, 70-75, and 57 kDa. IL2 induced tyrosine phosphorylation in YT 2C2 cells which express only the 75-kDa intermediate affinity IL2 binding molecule (IL2R beta) but not in cells which either express only the 55-kDa low affinity IL2 receptor molecule (IL2R alpha) or no IL2-binding sites. Therefore, IL2R beta, in the absence of IL2R alpha, appears sufficient to transduce the transmembrane signal leading to tyrosine phosphorylation. Two different antibodies reactive with phosphotyrosine specifically immunoprecipitated IL2R beta cross-linked to radiolabeled IL2. These findings suggest that IL2R beta is a substrate for the tyrosine kinase which is activated by IL2 binding to its receptor. Thus, like several other growth factor receptors, activation of the IL2R results in an increase in tyrosine phosphorylation with the receptor itself serving as one substrate.  相似文献
2.
We have isolated the full-length sequence for a unique human kinase, designated TTK. TTK was initially identified by screening of a T cell expression library with anti-phosphotyrosine antibodies. The kinases most closely related to TTK are the SPK1 serine, threonine and tyrosine kinase, the Pim1, PBS2, and CDC2 serine/threonine kinases, and the TIK kinase which was also identified through screening of an expression library with anti-phosphotyrosine antibodies. However, the relationships are distant with less than 25% identity. Nevertheless, TTK is highly conserved throughout phylogeny with hybridizing sequences being detected in mammals, fish, and yeast. TTK mRNA is present at relatively high levels in testis and thymus, tissues which contain a large number of proliferating cells, but is not detected in most other benign tissues. Freshly isolated cells from most malignant tumors assessed expressed TTK mRNA. As well, all rapidly proliferating cell lines tested expressed TTK mRNA. Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine. Taken together, these findings suggest that expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation.  相似文献
3.
The purpose of this study was to add to the growing database of cross-sectional areas and moment arm lengths of trunk musculature using the methods of computerized tomographic scanning. An attempt was also made to estimate muscle force and moment generating capacity under various reported values of muscle force per unit cross-sectional area. The data were obtained on 13 active men 40.5 +/- 11.9 years of age, 173.8 +/- 5.9 cm tall and 89.1 +/- 11.7 kg body mass. Transverse CT scans were taken at the level of the L4/L5 disc with the subjects supine. Muscle cross-sectional areas were measured from 35 mm slides of the scans using a planimeter and moment arm length in the transverse plane were taken from the centroid of the L4/L5 disc to the centroid of the muscle section. Prior to estimating force and moment generating capacity, areas were corrected, where necessary, for fibre pennation angle to produce a physiological cross-sectional area. The physiological cross-sectional areas (cm2) for one side of the body were (mean +/- S.D.): sacrospinalis (SS) 15.9 +/- 2.5; multifidus (Mu) 4.2 +/- 0.7; psoas (Ps) 17.6 +/- 4.0; rectus abdominis (RA) 7.9 +/- 2.5; external oblique (EO) 9.4 +/- 2.7; internal oblique (IO) 8.1 +/- 2.3; transverse abdominus (TA) 2.9 +/- 1.3. The anterior posterior moment arm lengths were: erector mass (SS and Mu combined) 5.90 +/- 0.52; Ps 0.58 +/- 0.40; R.A. 10.28 +/- 2.07; E.O. (anterior portion) 5.94 +/- 1.39; E.O. (posterior portion) 2.08 +/- 1.39; I.O. (anterior portion) 6.92 +/- 1.63; I.O. (posterior portion) 3.85 +/- 1.54. The corresponding lateral moment arm lengths were: 3.26 +/- 0.36; 4.88 +/- 0.36; 4.35 +/- 1.31; 12.86 +/- 1.93; 13.95 +/- 1.16; 10.77 +/- 2.02; 12.52 +/- 1.26. The maximum force per unit cross-section that human muscles are capable of generating is not well defined. However, assuming an intermediate value of 50 N cm-2 of physiological cross-section, the erector musculature observed at the L4/L5 level should be capable of generating an extensor moment of about 118 N.m. At a muscle stress of 30 or 90 N cm-2, values also reported on human muscle, the moment would be 71 and 213 Nm, respectively. It must be remembered, however, that muscles not observable at the L4/L5 level can create moments around that center of rotation.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献
4.
This work describes a dynamic model of the low back that incorporates extensive anatomical detail of the musculo-ligamentous-skeletal system to predict the load time histories of individual tissues. The dynamic reaction moment about L4/L5 was determined during lateral bending from a linked-segment model. This reaction moment was partitioned into restorative components provided by the disc, ligament strain, and active-muscle contraction using a second model of the spine that incorporated a detailed representation of the anatomy. Muscle contraction forces were estimated using both information from surface electromyograms, collected from 12 sites, and consideration of the modulating effects of muscle length, cross-sectional area and passive elasticity. This modelling technique is sensitive to the different ways in which individuals recruit their musculature to satisfy moment constraints. Time histories of muscle forces are provided. High muscle loads are consistent with the common clinical observation of muscle strain often produced by load handling. Furthermore, the coactivation measured in muscles on both sides of the trunk suggests that muscles are recruited to satisfy the lateral bending reaction torque in addition to performing other mechanical roles such as spine stabilization. If an estimate of the intervertebral joint compression is desired for assessment of lateral bends in industry, then a single equivalent lateral muscle with a moment arm of approximately 3.0-4.0 cm would conservatively capture the effects of muscle co-contraction quantified in this study.  相似文献
5.
6.
Biomechanical models utilized for analysis of tasks that load the lumbar spine often predict the resultant moment, disc compression and sometimes shear. Usually the extensor muscular and ligament forces of the lumbar spine are assumed to act 5 cm posterior to a disc centre of rotation. This study has re-examined the generation and pathways of muscular force transmission within the extensor musculature. The effects on L4/L5 disc compression and shear estimates of an anatomically and biomechanically justifiable range of tissue moment arms, lines of force and force generating capacity of muscle, input to a computer model, have been determined. Results indicated that L4/L5 compression estimates could be reduced by up to 35% when the output from a more realistic anatomical model of the erector spinae muscle group was compared with that from the frequently reported and simplified single muscle equivalent with a 5 cm moment arm. The shear force estimates could be altered from more than 500 N (L4 tending to shear anteriorly on L5) to less than 200 N with L4 tending to shear posteriorly on L5. Using the combination of input variables considered by the authors to be most feasible to estimate compression, a single 'equivalent' extensor soft tissue moment arm of 7.5 rather than 5 cm would be needed to equate the compression. This simplification of course, does not accommodate the shear force estimate problem.  相似文献
7.
The use of electromyographic signals in the modeling of muscle forces and joint loads requires an assumption of the relationship between EMG and muscle force. This relationship has been studied for the trunk musculature and been shown to be predominantly non-linear, with more EMG producing less torque output at higher levels of activation. However, agonist-antagonist muscle co-activation is often substantial during trunk exertions, yet has not been adequately accounted for in determining such relationships. The purpose of this study was to revisit the EMG-moment relationship of the trunk recognizing the additional moment requirements necessitated due to antagonist muscle activity. Eight participants generated a series of isometric ramped trunk flexor and extensor moment contractions. EMG was recorded from 14 torso muscles, and the externally resisted moment was calculated. Agonist muscle moments (either flexor or extensor) were estimated from an anatomically detailed biomechanical model of the spine and fit to: the externally calculated moment alone; the externally calculated moment combined with the antagonist muscle moment. When antagonist activity was ignored, the EMG-moment relationship was found to be non-linear, similar to previous work. However, when accounting for the additional muscle torque generated by the antagonist muscle groups, the relationships became, in three of the four conditions, more linear. Therefore, it was concluded that antagonist muscle co-activation must be included when determining the EMG-moment relationship of trunk muscles and that previous impressions of non-linear EMG-force relationships should be revisited.  相似文献
8.
    
9.
Assessment of the effects of lifting on the low back has most frequently been done with the aid of static models. Many lifting movements appear to have substantial inertial components. It was of interest, therefore, to determine the size of the difference between statically and dynamically calculated lumbar moments during a demanding but not unusual manual lift observed in a metal fabrication industry.

The results of several trials by four young men showed that the dynamic model resulted in peak L4 L5 moments 19% higher on average, with a maximum difference of 52%, than those determined from the static model. The technique adopted in the lift could minimize the difference. When the inertial forces of the load itself and the load weight were incorporated into an otherwise static model (quasi-dynamic) then the resulting L4/L5 moments exceeded those of the fully dynamic model by 25%.

In many industrial tasks static analyses may severely underestimate the demands of dynamic lifts. These results show that a reasonably inexpensive approach in lifting task analysis is to measure the dynamic forces of the load on the hands and to use these in an otherwise static model. This results in a conservative assessment of the injury risk of lifts at least of the type reported in this study.  相似文献

10.
While several sophisticated scientific approaches have been employed to understand low back function and injury mechanisms, very few have been broadly used to develop and justify injury prevention strategies. This paper looks beyond the linked segment model, and the lessons learned from this biomechanical approach, to consider the application of more sophisticated approaches. These include modelling approaches with greater anatomical and biological fidelity, fusing the lessons learned from the areas of tissue mechanics and concepts of spine stability, together with some studies that have examined several characteristics including psychosocial, physiological and personal variables. The objective is to better link recently discovered mechanisms of injury and spine tissue health with injury risk reducing approaches.  相似文献
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