Gap junctions and motor behavior

The production of any motor behavior requires coordinated activity in motor neurons and premotor networks. In vertebrates, this coordination is often assumed to take place through chemical synapses. Here we review recent data suggesting that electrical gap-junction coupling plays an important role in coordinating and generating motor outputs in embryonic and early postnatal life. Considering the recent demonstration of a prevalent expression of gap-junction proteins and gap-junction structures in the adult mammalian spinal cord, we suggest that neuronal gap-junction coupling might also contribute to the production of motor behavior in adult mammals.     

A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.      

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.     

Use of oral anticoagulants in older patients

Recently published American and British guidelines have comprehensively reviewed the indications for long term anticoagulation. The best evidence currently available supports the use of long term oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), venous thromboembolic disease, ischaemic heart disease, mural thrombi, and mechanical heart valves. Selected patients with valvular heart disease, cerebral vascular disease, and peripheral arterial disease may also benefit from the use of these drugs. When no specific contraindications are present, elderly patients with either paroxysmal or persistent NVAF should be considered candidates for treatment with anticoagulants. Pooled analyses of the results from 9 randomised trials demonstrate that warfarin significantly reduces the risk of ischaemic stroke in patients with NVAF, particularly those in a 'high risk' category defined by the presence of additional clinical or echocardiographic risk factors. Long term anticoagulation does not appear to be justified in patients with NVAF considered to be at 'low risk' for stroke. Because the prevalence of NVAF and most other cardiovascular conditions increases with advancing age, many elderly patients will be candidates for thromboprophylaxis. The potential benefit of long term anticoagulation must be carefully weighed against the risk of serious haemorrhage in such patients. Bleeding complications with anticoagulant drugs appear to occur more frequently in older patients than in younger individuals. Advanced age (>75 years), intensity of anticoagulation [International Normalised Ratio (INR) >4.0], history of cerebral vascular disease (recent or remote), and concomitant use of drugs that interfere with haemostasis [aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory drugs] are among the most important variables in determining an individual's risk for major bleeding with anticoagulants. Older patients often display increased sensitivity to the effects of warfarin, both in the early induction phase and during the long term maintenance phase of therapy. Conditions such as congestive heart failure, malignancy, malnutrition, diarrhoea and unsuspected vitamin K deficiency, enhance the prothrombin time response. The decision to interrupt anticoagulant therapy before elective surgery in elderly patients should evaluate the thrombotic risk of such a manoeuvre versus the risk of bleeding if anticoagulants are continued. In non-surgical patients, excessively elevated INRs without associated haemorrhage can usually be managed by simply witholding one or several doses of warfarin. If more rapid reversal is needed, small doses of phytomenadione (vitamin K1) can be administered safely without overcorrection or the development of vitamin K-induced warfarin resistance.     

B7-1和IL-12基因转染对肝癌细胞免疫原性的影响

目的 观察Ｂ７－１和ＩＬ－１２基因表达对人肝癌细胞免疫原性原影响。方法 分别将Ｂ７－１和ＩＬ－１２基因以逆转录病毒介导转染ＨｅｐＧ２细胞。阳性克隆细胞与健康人外周血淋巴细胞（ＰＢＬ）混合培养后,用流式细胞仪检测ＰＢＬ表面Ⅰ类人白细胞抗原（ＨＬＡ－Ⅰ）分子表达,以ＭＴＴ法检测ＰＢＬ的特异性杀伤活性Ｋ５６２细胞的活性。结果 混合ＨｅｐＧ２／Ｂ７－１ＨｅｐＧ２／ＩＬ－１２细胞组ＰＢＬ表面的ＨＬＡ－Ⅰ分子     

Handgrip strength in English schoolchildren

Aims: The aims of this study were to evaluate patterns of handgrip (HG) strength in relation to gender and age in English schoolchildren and to compare this with existing data and produce reference data for this population. Methods: The HG of 7147 English schoolchildren (3773 boys and 3374 girls) aged 10–15.9 years was measured using a portable Takei handgrip dynamometer (Takei Scientific Instruments Co. Ltd, Tokyo, Japan). Centile data were produced using the Generalized Additive Models for Location, Scale and Shape. Z‐scores were generated using existing data for European children. Age and gender interactions were analysed using analysis of covariance. Results: In boys and girls, significant increases in HG were found between every age‐group (p < 0.001). Boys were significantly stronger than girls at every age (p < 0.001) and the boys’ age‐related increase was significantly greater than the girls’ (p < 0.001). Conclusion: This study provides reference data for handgrip strength in English schoolchildren. Handgrip strength in English children is broadly similar to existing European data, after adjusting for mass and stature. These data could be used for clinical or athletic screening of low and high strength in this population.