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961.
962.
Spine biomechanics   总被引:2,自引:0,他引:2  
Current trends in spine research are reviewed in order to suggest future opportunities for biomechanics. Recent studies show that psychosocial factors influence back pain behaviour but are not important causes of pain itself. Severe back pain most often arises from intervertebral discs, apophyseal joints and sacroiliac joints, and physical disruption of these structures is strongly but variably linked to pain. Typical forms of structural disruption can be reproduced by severe mechanical loading in-vitro, with genetic and age-related weakening sometimes leading to injury under moderate loading. Biomechanics can be used to quantify spinal loading and movements, to analyse load distributions and injury mechanisms, and to develop therapeutic interventions. The authors suggest that techniques for quantifying spinal loading should be capable of measurement "in the field" so that they can be used in epidemiological surveys and ergonomic interventions. Great accuracy is not required for this task, because injury risk depends on tissue weakness as much as peak loading. Biomechanical tissue testing and finite-element modelling should complement each other, with experiments establishing proof of concept, and models supplying detail and optimising designs. Suggested priority areas for future research include: understanding interactions between intervertebral discs and adjacent vertebrae; developing prosthetic and tissue-engineered discs; and quantifying spinal function during rehabilitation. "Mechanobiology" has perhaps the greatest future potential, because spinal degeneration and healing are both mediated by the activity of cells which are acutely sensitive to their local mechanical environment. Precise characterisation and manipulation of this environment will be a major challenge for spine biomechanics.  相似文献   
963.
964.
Aron R  Lopez N  Walter W  Craig EA  Johnson J 《Genetics》2005,169(4):1873-1882
The essential Hsp40, Sis1, is a J-protein cochaperone for the Ssa class of Hsp70's of Saccharomyces cerevisiae. Sis1 is required for the maintenance of the prion [RNQ(+)], as Sis1 lacking its 55-amino-acid glycine-rich region (G/F) does not maintain [RNQ(+)]. We report that overexpression of Sis1DeltaG/F in an otherwise wild-type strain had a negative effect on both cell growth and [RNQ(+)] maintenance, while overexpression of wild-type Sis1 did not. Overexpression of the related Hsp40 Ydj1 lacking its G/F region did not cause inhibition of growth, indicating that this dominant effect of Sis1DeltaG/F is not a characteristic shared by all Hsp40's. Analysis of small deletions within the SIS1 G/F region indicated that the observed dominant effects were caused by the absence of sequences known to be important for Sis1's unique cellular functions. These inhibitory effects of Sis1DeltaG/F were obviated by alterations in the N-terminal J-domain of Sis1 that affect interaction with Ssa's ATPase domain. In addition, a genetic screen designed to isolate additional mutations that relieved these inhibitory effects identified two residues in Sis1's carboxy-terminal domain. These alterations disrupted the interaction of Sis1 with the 10-kD carboxy-terminal regulatory domain of Ssa1, indicating that Sis1 has a bipartite interaction with Ssa in vivo.  相似文献   
965.
Zee RY  Cook NR  Reynolds R  Cheng S  Ridker PM 《Genetics》2005,169(3):1583-1587
Polymorphisms in the beta2 adrenergic receptor (ADRB2), in particular G16R, Q27E, and T164I, have been implicated in the pathogenesis of cardiovascular and metabolic phenotypes. However, no prospective, genetic-epidemiological data are available on the risk of cardiovascular disease associated with these variants. Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated the G16R, Q27E, and T164I polymorphisms among 523 individuals who subsequently developed myocardial infarction and among 2092 individuals who remained free of reported cardiovascular events during follow-up. The haplotype frequency distribution was significantly different among cases and controls (chi(2)(7d.f.) = 20.92, P = 0.0039). Haplotype-based logistic regression, adjusting for age, smoking, and randomized treatment group, indicated that G16-Q27-I164 (odds ratio 0.178, 95% C.I. 0.043-0.737, P = 0.017) and (non-G16-Q27)-T164 (odds ratio 1.235, 95% C.I. 1.031-1.480, P = 0.022) haplotypes were significantly associated with altered risk of myocardial infarction. These findings remained after further adjustment for BMI, history of hypertension, and presence or absence of diabetes. In conclusion, variation in haplotype frequencies for the beta2 adrenergic receptor gene was found to be associated with risk of myocardial infarction.  相似文献   
966.
Growth hormone (GH) regulates many of the factors responsible for controlling the development of bone marrow progenitor cells (BMPCs). The aim of this study was to elucidate the role of GH in osteogenic differentiation of BMPCs using GH receptor null mice (GHRKO). BMPCs from GHRKO and their wild-type (WT) littermates were quantified by flow cytometry and their osteogenic differentiation in vitro was determined by cell morphology, real-time RT-PCR, and biochemical analyses. We found that freshly harvested GHRKO marrow contains 3% CD34 (hematopoietic lineage), 43.5% CD45 (monocyte/macrophage lineage), and 2.5% CD106 positive (CFU-F/BMPC) cells compared to 11.2%, 45%, and 3.4% positive cells for (WT) marrow cells, respectively. When cultured for 14 days under conditions suitable for CFU-F expansion, GHRKO marrow cells lost CD34 positivity, and were markedly reduced for CD45, but 3- to 4-fold higher for CD106. While WT marrow cells also lost CD34 expression, they maintained CD45 and increased CD106 levels by 16-fold. When BMPCs from GHRKO mice were cultured under osteogenic conditions, they failed to elongate, in contrast to WT cells. Furthermore, GHRKO cultures expressed less alkaline phosphatase, contained less mineralized calcium, and displayed lower osteocalcin expression than WT cells. However, GHRKO cells displayed similar or higher expression of cbfa-1, collagen I, and osteopontin mRNA compared to WT. In conclusion, we show that GH has an effect on the proportions of hematopoietic and mesenchymal progenitor cells in the bone marrow, and that GH is essential for both the induction and later progression of osteogenesis.  相似文献   
967.
Gammadelta T cells suppress airway hyperresponsiveness (AHR) induced in allergen-challenged mice but it is not clear whether the suppression is allergen specific. The AHR-suppressive cells express TCR-Vgamma4. To test whether the suppressive function must be induced, we adoptively transferred purified Vgamma4(+) cells into gammadelta T cell-deficient and OVA-sensitized and -challenged recipients (B6.TCR-Vgamma4(-/-)/6(-/-)) and measured the effect on AHR. Vgamma4(+) gammadelta T cells isolated from naive donors were not AHR-suppressive, but Vgamma4(+) cells from OVA-stimulated donors suppressed AHR. Suppressive Vgamma4(+) cells could be isolated from lung and spleen. Their induction in the spleen required sensitization and challenge. In the lung, their function was induced by airway challenge alone. Induction of the suppressors was associated with their activation but it did not alter their ability to accumulate in the lung. Vgamma4(+) gammadelta T cells preferentially express Vdelta4 and -5 but their AHR-suppressive function was not dependent on these Vdeltas. Donor sensitization and challenge not only with OVA but also with two unrelated allergens (ragweed and BSA) induced Vgamma4(+) cells capable of suppressing AHR in the OVA-hyperresponsive recipients, but the process of sensitization and challenge alone (adjuvant and saline only) was not sufficient to induce suppressor function, and LPS as a component of the allergen was not essential. We conclude that AHR-suppressive Vgamma4(+) gammadelta T cells require induction. They are induced by allergen stimulation, but AHR suppression by these cells does not require their restimulation with the same allergen.  相似文献   
968.
Factor H-related protein 5 (FHR-5) is a recently discovered member of the factor H (fH)-related protein family. FHR proteins are structurally similar to the complement regulator fH, but their biological functions remain poorly defined. FHR-5 is synthesized in the liver and consists of 9 short consensus repeats (SCRs), which display various degrees of homology to those of fH and the other FHR proteins. FHR-5 colocalizes with complement deposits in vivo and binds C3b in vitro, suggesting a role in complement regulation or localization. The current study examined whether rFHR-5 exhibits properties similar to those of fH, including heparin binding, CRP binding, cofactor activity for the factor I-mediated degradation of C3b and decay acceleration of the C3 convertase. rFHR-5 bound heparin-BSA and heparin-agarose and a defined series of truncations expressed in Pichia pastoris localized the heparin-binding region to within SCRs 5-7. rFHR-5 bound CRP, and this binding was also localized to SCRs 5-7. FHR-5 inhibited alternative pathway C3 convertase activity in a fluid phase assay; however, dissociation of the convertase was not observed in a solid phase assay. rFHR-5 displayed factor I-dependent cofactor activity for C3b cleavage, although it was apparently less effective than fH. In addition, we demonstrate association of FHR-5 with high density lipid lipoprotein complexes in human plasma. These results demonstrate that FHR-5 shares properties of heparin and CRP binding and lipoprotein association with one or more of the other FHRs but is unique among this family of proteins in possessing independent complement-regulatory activity.  相似文献   
969.
970.
Hypoxia-inducible factor-1 (HIF) is regulated by oxygen-dependent prolyl hydroxylation. Of the three HIF prolyl hydroxylases (PHD1, 2 and 3) identified, PHD3 exhibits restricted substrate specificity in vitro and is induced in different cell types by diverse stimuli. PHD3 may therefore provide an interface between oxygen sensing and other signalling pathways. We have used co-purification and mass spectrometry to identify proteins that interact with PHD3. The cytosolic chaperonin TRiC was found to copurify with PHD3 in extracts from several cell types. Our results indicate that PHD3 is a TRiC substrate, providing another step at which PHD3 activity may be regulated.  相似文献   
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