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Joseph M Dhahbi Shelley X Cao Patricia L Mote Brian C Rowley John E Wingo Stephen R Spindler 《The Journal of nutrition》2002,132(1):31-37
Molecular chaperones assist in the biosynthesis and processing of proteins. Most chaperones are induced by physiological stresses. We have shown that dietary energy restriction decreases the mRNA and protein levels of many endoplasmic reticulum chaperones in the livers of mice. Here, we have investigated the response of chaperone mRNA to feeding. Control and 50% energy-restricted C3B10RF1 mice were deprived of food for 24 h, fed, and killed 0, 1.5, 5 or 12 h after feeding. Chaperone mRNAs were strongly induced as early as 1.5 h after feeding in control and energy-restricted mice. The integrated levels of these mRNA over 24 h were significantly lower in energy-restricted mice. The mRNA response to energy intake was mirrored over the course of days in the level of chaperone protein. A similar but smaller response to feeding was found in kidney and muscle. Puromycin and cycloheximide failed to inhibit the feeding response, suggesting that feeding releases chaperone expression from an unstable inhibitor. Studies with dibutyryl-cAMP- and glucagon-supplemented, normal and streptozotocin-diabetic mice suggest that glucagon and insulin may be mediators of the feeding response. Adrenalectomy enhanced the feeding induction, but dexamethasone administration had no effect. Thus, postprandial changes in insulin and glucagon may link chaperone gene expression to feeding, possibly in several tissues including liver. 相似文献
74.
Many important pharmaceutical agents, including vancomycin, bleomycin, cyclosporin, and several antibiotics, are produced by non‐ribosomal peptide synthetase (NRPS) enzymes in microorganisms. The NRPS pathway produces an extensive library of products using multienzyme complexes acting in an assembly‐line fashion. Engineering an NRPS system to produce an even greater variety of products, some of which may also have beneficial therapeutic value, would be an enormous advantage. Several approaches have been successful in generating novel NRPS products: mutational biosynthesis during which nonnatural substrates are fed to an organism; domain and module swapping between different species to generate hybrid enzymes; and rational site‐directed mutagenesis, based either on phylogeny or computational prediction, intended to switch substrate specificity and produce altered products. This review will highlight the progress in these areas and describe research in the future that will extend the capacity for re‐engineering NRPS systems. Drug Dev. Res. 66:9–18, 2006. © 2006 Wiley‐Liss, Inc. 相似文献
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经皮穿刺髓核成形术治疗腰椎间盘突出症初步临床报道 总被引:36,自引:2,他引:34
目的 寻求一种简单、安全、有效、微创的椎间盘突出症治疗方法。方法 对 1 6例腰椎间盘突出症采用经皮穿刺髓核成形术 (Nucleoplasty)治疗 ,并对其疗效进行观察分析。 结果 全部患者经二周至一个月短期随访 ,症状均有不同程度改善 ,疗效优良率为 93 8% ,有效率为 1 0 0 %。未发现明显并发症。结论 髓核成形术是一种先进、安全、有效的椎间盘突出微创手术 ,具有操作简单、安全、微创、疗效佳、恢复快、无需住院等优点。 相似文献
77.
烹调油烟致大小鼠肺癌的实验研究 总被引:1,自引:0,他引:1
[目的]了解烹调油烟(cooking oil fumes,COF)的动物致癌性。[方法]采用动式染毒法给Balb/c小鼠(雌雄各半)吸入COF浓度为9.09、20.65、38.85mg/m^3,染毒1次/1~2d,30min/次,共150次,计8个月;SD大鼠(雌雄各半)吸入COF浓度为6、88、15.06、35.33mg/m^3,染毒1次/2d,30min/次,共191次,计12.5个月。分别制备COF慢性中毒动物模型;两实验均设空白对照组,吸入与实验组相同温度的清洁空气。[结果]COF诱发Balb/c小鼠实验组肺癌总发生率为18、95%(29/153),低、中、高浓度组肺癌发生率分别为15.09%、20、00%和22.00%,与对照组差异均有显著性。但低、中、高三组间差异无显著性(P〉0.05);COF诱发SD大鼠肺癌总发生率为9、10%(9/99),低、中、高浓度组肺癌发生率分别为6.45%、8.57%、12.12%,高浓度组肺癌发生率高于对照组(P〈0.05)。各性别组间肺癌发生率的差别无显著性(P〉0.05)。[结论]COF可以诱导Balb/c小鼠和SD大鼠肺癌,诱发的肺癌主要为肺腺癌(小鼠28/29,大鼠7/9),余为小细胞肺癌。 相似文献
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79.
Paul Hochstein Ulrich Glatzel Thomas Schmickal Andreas Wentzensen 《Trauma und Berufskrankheit》2002,4(2):s110-s114
The treatment of deep cartilage defects in load-bearing joints is a problem that still has no satisfactory solution. Full-thickness defects of the articular cartilage rarely heal spontaneously, usually leaving damage that can lead to early arthrosis. Techniques currently available for the treatment of chondral defects include abrasion, drilling, micro-fracturing, transplantation of tissue autografts and allografts, and cell transplantation. Osteochondral autograft transplantation is currently the only surgical cartilage repair technique known to lead to the formation of genuine hyaline articular cartilage and its retention at least in the medium term. The Draenert method, in which a water-cooled diamond bone-cutting system is used, is an effective procedure for resurfacing the joints affected by localised cartilaginous defects, even when there is also severe bone loss. Donor-side morbidity can be kept to a minimum by filling the defect caused by harvesting with a press-fit cylinder of cancellous bone covered with periosteum for protection. 相似文献
80.
Annemieke Smit-van Oosten Winston W. Bakker Harry van Goor 《Transplant international》2002,15(12):602-609
Ischemic injury plays an important role in chronic renal transplant failure (CRTF). Down-regulation of ecto-adenosine triphosphatase (ATPase) in combination with up-regulation of ecto-5'-nucleotidase is a hallmark of ischemic injury. We studied the expression of renal ecto-5'-nucleotidase and ecto-ATPase in experimental renal transplantation. Fisher 344-to-Lewis allografted rats were either treated with an angiotensin-converting enzyme inhibitor (ACEi) or left untreated. Lewis-to-Lewis syngrafted rats served as controls. Untreated allografted rats developed proteinuria, glomerulosclerosis, and mild intimal hyperplasia. ACEi completely prevented focal and segmental glomerulosclerosis (FGS) and proteinuria, but significantly enhanced intimal hyperplasia. Untreated allografted rats revealed marked vascular ecto-5'-nucleotidase activity, which increased with ACEi. Vascular ecto-5'-nucleotidase activity was absent in syngrafted animals. Ecto-5'-nucleotidase activity correlated well with intimal hyperplasia. Glomerular ecto-ATPase expression was significantly reduced in untreated allografted rats compared to syngrafted rats and correlated well with the extent of FGS. ACEi prevented reduction in glomerular ecto-ATPase. We found de-novo expression of ecto-5'-nucleotidase at sites of renal intimal hyperplasia. Glomerular ecto-ATPase expression was markedly reduced in allografted rats and was prevented by ACEi. These enzyme expression patterns suggest local ischemic damage in experimental CRTF. 相似文献