THAP11通过抑制p53的泛素化影响食管癌细胞的增殖和凋亡

目的：探讨死亡相关蛋白(thanatos-associated protein,THAP)11对食管癌细胞增殖和凋亡的影响及其潜在 的机制。方法：采用蛋白质印迹法检测人食管上皮细胞Het-1A和人食管癌细胞(Eca109,TE-1和Ec 9706)中THAP11的 表达。将食管癌TE-1细胞分为空白对照(NC)组、阴性对照(LV-LC)组、TRA P11(LV-TRA P11)组,按分组处理细胞后, 采用MTT 法检测细胞活力,流式细胞术检测细胞凋亡,caspases试剂盒检测caspase-3和caspase-9的活性。采用体外泛素 化实验检测TE-1细胞的p53泛素化水平。结果：与Het-1A细胞相比,食管癌细胞中THAP11的表达显著下降(P<0.05)。 LV-THAP11转染食管癌细胞后,细胞活力降低(P<0.05),凋亡率升高(P<0.05),caspase-3和caspase-9活性升高(P<0.05)。 THAP11能够提高食管癌细胞中p53蛋白的表达(P<0.05)。与LV-LC组相比,转染THAP11后食管癌细胞中p53的表达上调 (P<0.05),MDM2调节的p53的泛素化也被抑制。结论：THAP11通过抑制p53的泛素化抑制食管癌细胞的增殖,促进食管 癌细胞的凋亡。     

国人无综合征性耳聋患者的线粒体基因组7445A→G突变263例调查

目的 :探讨国人无综合征性耳聋 ( NSD)患者的线粒体 DNA 744 5 A→ G( m t DNA744 5 A→ G)突变的发生情况。方法 :对 32个 NSD家系 12 8例和 135例散发的 NSD患者 ,10 0例正常人 ,以 PCR法检测 mt DNA 744 5 A→ G突变情况。结果 :全部受检者无 mt DNA744 5 A→ G突变发生。结论 :国人 NSD患者的 m t DNA744 5 A→ G突变的发生率较低 ,且明显低于 mt DNA15 5 5 A→ G的突变发生率     

Novel developments with selective, non-peptidic kappa-opioid receptor agonists

Despite the recent introduction of a number of new compounds, there has of late been a cooling of interest by pharmaceutical companies in the development of centrally-active, selective kappa opioid agonists for therapeutic purposes. This is reflected in the discontinuation of a number of clinical trials, for reasons that are often not completely clear to outside observers. Spiradoline and enadoline have apparently been abandoned as potential analgesics because they induce dose-limiting central side-effects (i.e., dysphoria) in models of post-surgical pain. The development of niravoline as an aquaretic for the treatment of cirrhosis with ascites and other hyponatraemic disorders has also been halted. Enadoline may yet find some application against ischaemic stroke and severe head injury, presumably in comatose patients in whom psychiatric side-effects are taken to be immaterial, while apadoline and TRK 820 remain in Phase II clinical testing against cancer pain. The peripherally-selective kappa agonists, asimadoline, and the atypical compound, fedotozine, are well-tolerated in man. Results of Phase III trials of fedotozine against irritable bowel syndrome and dyspepsia have, however, ultimately been disappointing, whereas asimadoline is currently in Phase II clinical trials against pain of rheumatic and osteoarthritic origin. The results of these trials are eagerly awaited.     

Laboratory toxicology of six forestry insecticides to four species of bee (hymenoptera: Apoidea)

Laboratory dose-response studies were conducted with four species of adult bees, Apis mellifera (workers), Andrena erythronii (females), Megachile rotundata (females), and Bombus terricola (workers), using six insecticides, permethrin, mexacarbate, aminocarb, fenitrothion, carbaryl, and trichlorfon. All insecticides were applied topically to the thorax of the bees as technical grade in an acetone carrier. Mortality was accumulated over 48 h, and probit analyses were conducted separately on data sets expressed in units of gAI (active ingredient)/g body weight and of gAI/bee. LD₅₀ values with 95% confidence limits and slopes with standard errors are provided for each bee/insecticide combination in each data set. Relative toxicities, relative susceptibilities, and fresh body weights are also provided. The analysis in units of gAI/g body weight indicated that the insecticides were typically ranked in order of decreasing toxicity—permethrin, mexacarbate, aminocarb, fenitrothion, carbaryl, and trichlorfon. Likewise, the bees ranked from the most to least susceptible in the order of A. mellifera, A. erythronii, M. rotundata and B. terricola. Trends within the data set for units of gAI/bee were less consistent. These data are discussed and compared with other published data on the toxicology of insecticides to bees and from the perspective of risk assessment.     

The effects of alcohol abuse on children and the partner's capacity to initiate change

This paper identifies the social, psychological and cognitive effects of parental alcohol abuse on children across the lifecycle. While the evidence regarding cognitive effects is mixed, there is ample evidence of negative effects on a range of developmental outcomes. Recent advances in unilateral partner interventions open up one avenue for ameliorating this damage even when the drinker is resistant to change.     

舰艇环境对舰员心理功能和神经行为的影响

探讨封闭型舰艇环境对舰员心理功能和神经行为的影响。方法 采用微机化神经行为评价系统和症状自评量表对封闭型水面舰艇舰员进行了测试,并以开放型水面舰艇舰员为对照。结果 封闭型舰艇人员符号译码成绩明显低于开放型舰艇人员,并出现类似“空调病”的症状。结论封闭型舰艇环境能危害舰员的心理健康,负离子浓度低为重要的环境因素,应改进通风。     

Present and future studies on lipogenesis in animals and human subjects

Lipogenesis occurs in all vertebrate species and has a critical role in energy balance, providing a means whereby excess energy can be stored as a fat. The metabolic pathways involved and their tissue distribution in different species, including man, are well known. The responses of lipogenesis to diet and to physiological and pathological states have been the subject of many studies. At a molecular level the major rate-controlling enzymes have been identified and their acute, and to a lesser extent chronic, control by hormones have been investigated extensively. However, there is no reason to suppose that all factors regarding lipogenesis have been identified (e.g. the recent discovery of acylation-stimulating protein). Little is known about the movement of newly-synthesized triacylglycerols in cells, either for secretion or storage. The production of leptin and tumour necrosis factor alpha by adipocytes provides a novel means of feedback control of triacylglycerol production, leptin by decreasing appetite and tumour necrosis factor alpha by inducing insulin resistance. The synthesis of these peptides appears to vary with the amount of triacylglycerol in adipocytes, but the molecular basis of this process is unknown. Elucidation of the signalling systems involved in the acute and chronic regulation of lipogenesis is also important, both with respect to some homeorhetic adaptations and also in some pathological conditions (e.g. non-insulin-dependent diabetes). Finally, molecular biology is revealing unexpected complexities, such as multiple promoters and different isoforms of enzymes (e.g. acetyl-CoA carboxylase; EC 6.4.1.2) exhibiting tissue specificity. Molecular biology, through transgenesis, also offers novel and powerful means of manipulating lipogenesis.     

Medial temporal lobe atrophy on MRI in dementia with Lewy bodies

OBJECTIVE: To investigate whether medial temporal lobe atrophy (MTA) on MRI is less frequent in dementia with Lewy bodies (DLB) compared with AD and vascular dementia (VaD), and to determine the diagnostic utility of MTA in the differential diagnosis of dementia. METHOD: Coronal T1-weighted 1.0-T MR images were acquired in patients with DLB (consensus criteria; n = 26; mean age, 75.9 years), AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; n = 28; mean age, 77.4 years), VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences; n = 24; mean age, 76.9 years), and normal control subjects (n = 26; mean age, 76.2 years). Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized scale. RESULTS: MTA was more frequent and severe in all dementia groups compared with control subjects (AD, 100%; VaD, 88%; DLB, 62%; control subjects, 4%; p < 0.001). Comparing dementia groups, MTA scores were significantly lower in DLB than AD (p = 0.002), with a trend toward less atrophy in DLB compared with VaD (p = 0.07). The absence of MTA had a specificity of 100% and 88% for separating DLB from AD and VaD respectively, and a sensitivity of 38%. In patients with DLB, MTA increased with age (r = 0.58, p = 0.002), and in all dementia patients MTA correlated with memory impairment (combined memory score, r = -0.34, p = 0.003) but not total CAMCOG score or other subscales. CONCLUSION: Patients with DLB have significantly greater MTA than control subjects but significantly less than those with AD. The authors confirmed that the presence of MTA is useful in detecting AD but less useful in differentiating between dementias. However, in the differentiation of DLB from AD and VaD, the absence of MTA is highly suggestive of a diagnosis of DLB.     

Fulcrum for the future: the creation of a values-driven culture

This article describes the efforts of a small children's specialty hospital to prepare for a difficult period of restructuring in the marketplace by using the organization's core values as a force for direction, stabilization, and leverage. A best practices model was used to identify values that were a central part of the hospital's cultural heritage but were also critical for ensuring future institutional success. Principles for values definition and implementation provide guidance for other health care institutions.