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31.
Elhaji Youssef A.; Stoica Ileana; Dennis Sheldon; Purisima Enrico O.; Lumbroso Rose; Beitel Lenore K.; Trifiro Mark A. 《Human molecular genetics》2006,15(9):1561
Human Molecular Genetics (2006) 15, 921931; 相似文献
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Alex N. Bullock Julia Henckel Brian S. DeDecker Christopher M. Johnson Penka V. Nikolova Mark R. Proctor David P. Lane Alan R. Fersht 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(26):14338-14342
Some 50% of human cancers are associated with mutations in the core domain of the tumor suppressor p53. Many mutations are thought just to destabilize the protein. To assess this and the possibility of rescue, we have set up a system to analyze the stability of the core domain and its mutants. The use of differential scanning calorimetry or spectroscopy to measure its melting temperature leads to irreversible denaturation and aggregation and so is useful as only a qualitative guide to stability. There are excellent two-state denaturation curves on the addition of urea that may be analyzed quantitatively. One Zn2+ ion remains tightly bound in the holo-form of p53 throughout the denaturation curve. The stability of wild type is 6.0 kcal (1 kcal = 4.18 kJ)/mol at 25°C and 9.8 kcal/mol at 10°C. The oncogenic mutants R175H, C242S, R248Q, R249S, and R273H are destabilized by 3.0, 2.9, 1.9, 1.9, and 0.4 kcal/mol, respectively. Under certain denaturing conditions, the wild-type domain forms an aggregate that is relatively highly fluorescent at 340 nm on excitation at 280 nm. The destabilized mutants give this fluorescence under milder denaturation conditions. 相似文献
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It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs. 相似文献
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Lucy Yardley David Papo Adolfo Bronstein Michael Gresty Mark Gardner Nilli Lavie Linda Luxon 《Neuropsychologia》2002,40(4):373-383
The aim of this series of experiments was to determine whether attention is normally required for continuously processing vestibular information concerning orientation, or is required only when orientation is disrupted (eg by vestibular dysfunction or by conflicting visual and vestibular orientation cues). In the first two studies, healthy subjects were passively oscillated, and indicated when they perceived they were passing through their starting position. There was only weak evidence for interference between performance on this 'continuous orientation monitoring task' and on concurrent mental tasks. However, a third study showed that when patients with vestibular imbalance carried out the continuous orientation monitoring task their performance on a concurrent mental arithmetic task was substantially impaired. This dual task interference was correlated with inaccuracy in judging orientation on the continuous orientation monitoring task, which in turn correlated with severity of recent vestibular symptomatology (assessed by questionnaire). In a fourth experiment, disorientation was induced in healthy subjects by rotating the visual field about the line of sight. Bidirectional interference was observed between monitoring orientation (assessed by accuracy in setting a rod to the perceived vertical) and performance of an arithmetic task. Dual task interference was correlated with baseline levels of disorientation induced by the visual field, as indicated by inaccuracy in judging the visual vertical. These findings suggest that monitoring orientation makes significant demands upon cortical processing resources when disorientation is induced, whether the disorientation results from deficient sensory functioning or from ambiguous perceptual information. 相似文献
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Xiaoguang Chen Yi Li Lei Wang Mark Katakowski Lijie Zhang Jieli Chen Yongxian Xu Subhash C. Gautam Michael Chopp 《Neuropathology》2002,22(4):275-279
Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain. 相似文献
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OBJECTIVE: The authors examined whether physicians' use of computerized decision aids affects patient satisfaction and/or blame for medical outcomes. METHOD: Experiment 1: Fifty-nine undergraduates read about a doctor who made either a correct or incorrect diagnosis and either used a decision aid or did not. All rated the quality of the doctor's decision and the likelihood of recommending the doctor. Those receiving a negative outcome also rated negligence and likelihood of suing. Experiment 2: One hundred sixty-six medical students and 154 undergraduates read negative-outcome scenarios in which a doctor either agreed with the aid, heeded the aid against his own opinion, defied the aid in favor of his own opinion, or did not use a decision aid. Subjects rated doctor fault and competence and the appropriateness of using decision aids in medicine. Medical students made judgments for themselves and for a layperson. RESULTS: Experiment 1: Using a decision aid caused a positive outcome to be rated less positively and a negative outcome to be rated less negatively. Experiment 2: Agreeing with or heeding the aid was associated with reduced fault, whereas defying the aid was associated with roughly the same fault as not using one at all. Medical students were less harsh than undergraduates but accurately predicted undergraduate's responses. CONCLUSION: Agreeing with or heeding a decision aid, but not defying it, may reduce liability after an error. However, using an aid may reduce favorability after a positive outcome. 相似文献
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