FoxD3在胚胎发育和维持胚胎干细胞多能性的作用

学术背景：胚胎干细胞无论对转基因动物的制备还是对疾病的治疗都具有巨大的潜能，但前提是用于治疗的胚胎干细胞具有其特有的多能性和全能性，而FoxD3在胚胎发育和维持胚胎干细胞多能性都具有重要作用。目的：了解FoxD3在胚胎发育和维持胚胎干细胞多能性的作用。检索策略：应用计算机检索Pubmed1996—09／2007—05期间的相关文章，检索词为“FoxD3”，限定语言种类为英文。检索到67篇文章，排除重复的和与胚胎发育和胚胎干细胞相关性不大的文章，共纳入32篇文献。文献评价：32篇文献中分别涉及胚胎干细胞转录调节、FoxD3在胚胎发育和维持胚胎干细胞多能性的作用及其Foxd3在其他细胞中（骨髓细胞、神经嵴细胞、色素细胞）的功能等方面的内容,资料综合：胚胎干细胞具有其他细胞不可比拟的特性使胚胎干细胞应用广泛，要合理控制胚胎干细胞在体内和体外的分化，关键要了解那些控制胚胎干细胞命运的基因。FoxD3是叉头框（Forkheadbox，Fox）家族中的一个转录调控因子，它对胚胎上胚层及其衍生物的形成和建立多潜能胚胎干细胞系具有重要作用，并与控制胚胎发育和胚胎干细胞多能性的其他转录调控因子有一定的联系。结论：FoxD3是维持胚胎上胚层细胞多潜能性和在体外建立胚胎干细胞系所必需的。     

Are adverse events of nevirapine and efavirenz related to plasma concentrations?

OBJECTIVE: The relationships between adverse events (AEs) and plasma concentrations of nevirapine (NVP) and efavirenz (EFV) were investigated as part of the large, international, randomized 2NN study. METHODS: Treatment-naive, HIV-1-infected patients received NVP (once or twice daily), EFV or their combination, each in combination with lamivudine and stavudine. Blood samples were collected on day 3 and weeks 1, 2, 4, 24 and 48. Concentrations of NVP and EFV were quantitatively assessed by a validated HPLC assay. Individual Bayesian estimates of the area under the plasma concentration-time curve over 24 h (AUC24h), and minimum and maximum plasma concentrations (Cmin and Cmax) as measures for drug exposure of NVP and EFV, were generated using a previously developed population pharmacokinetic model. Pharmacokinetic parameters were compared for patients with and without central nervous system (CNS) and psychiatric AEs, hepatic events, liver enzyme elevations (LEEs) and rash. Furthermore, it was investigated whether a clear cut-off for a pharmacokinetic parameter could be identified above which the incidence of AEs was clearly increased. AEs were also related to demographic parameters and baseline characteristics. RESULTS: In total, from 1077 patients, NVP (3024 samples) and EFV (1694 samples) plasma concentrations and AE data (825 observations) were available. For all patients Cmin, Cmax and AUC24h were determined. When corrected for known covariates of gender, CD4 cell count at baseline, region, hepatitis coinfection and possible interactions between these factors, no significant associations between AEs and any tested exposure parameter of NVP was observed. Also, no target Cmin value, above which patients were at increased risk for AEs, could be established. On the other hand, geographical region, hepatitis coinfection, CD4 cell count and gender were found to be significantly related with the incidence of CNS and psychiatric AEs, hepatic events, LEEs and rash during the treatment with NVP. The occurrence of elevated liver enzymes during the first 6 weeks in the EFV-containing arm was significantly (P = 0.036) correlated to the exposure of EFV (Cmin). Only hepatitis coinfection impacted on LEEs during the first 6 weeks of treatment. With an EFV Cmin above 2.18 mg/l during the induction phase, patients were 4.4 (range 1.3-15.5) times more at risk for elevated liver enzymes. No other correlations between AEs and EFV pharmacokinetics or patient characteristics could be identified. CONCLUSIONS: Pharmacokinetic parameters of NVP did not have a relationship to AEs in the 2NN trial when corrected for known covariates. The value of periodical drug monitoring of NVP as a way to prevent toxicity is therefore limited. Treating physicians should instead focus on factors that are more predictive of AEs (gender, CD4 count and hepatitis coinfection). High EFV Cmin levels resulted in elevated liver enzyme values during the first 6 weeks of treatment. Regular measurement of EFV levels and liver enzymes at the start of therapy may therefore be advised.     

Effect of Rous sarcoma virus on cytoplasmic membranes of sensitive and resistant cells

An increase in cholesterol and sialic acid levels in cytoplasmic membranes was registered in the course of Rous sarcoma-induced transformation of chick embryo cells. There was no such effect in virus-resistant human cells.     

EGF促进RPE细胞β_2肾上腺能受体诱导的cAMP形成：受体间交互作用分析

研究证实表皮生长因子（ＥＧＦ）不影响培养人眼视网膜色素上皮（ＲＰＥ）细胞ｃＡＭＰ的基础水平，但促进异丙肾上腺素激活β＿２受体后诱导ｃＡＭＰ水平升高的效应，并呈量效依赖关系。ＥＧＦ对腺嘌呤核苷Ａ＿２受体激动剂ＮＥＣＡ诱导ｃＡＭＰ水平升高的效应没有明显影响。细胞增殖分析表明，ＥＧＦ刺激人眼ＲＰＥ细胞增殖，而ＤｉｂｕｔｙｒｙｌｃＡＭＰ和异丙肾上腺素抑制ＥＧＦ刺激增殖的效应。结果提示，在人眼ＲＰＥ细胞ＥＧＦ和β２受体之间存在受体间交互作用。     

Evaluating a computer system used as a microswitch for word utterances of persons with multiple disabilities

Purpose: To assess the effectiveness of a computer system used as a microswitch for word utterances of two adults with multiple disabilities. The system combined a new control software programme with a commercially available speech recognition programme. Method: Nine word utterances were targeted for each participant. The participant's emission of those utterances triggered the occurrence of related (favourite) stimuli during the intervention and the post-intervention check. Results: Intervention data showed that (1) the participants increased the frequencies of the target utterances and (2) the computer system recognized about 80% of those utterances correctly, providing the participants with high levels of favourite stimulation. The post-intervention check showed comparable data with both participants. Conclusions: The computer system proved an adequate microswitch for word utterances. Based on this evidence, microswitch programmes could be extended beyond the use of conventional motor responses.     

Vitamin A intake and xerophthalmia among Indian children

OBJECTIVE: To estimate prevalence of xerophthalmia and to assess dietary intake of vitamin A in Indian children aged under 6 y. DESIGN: Cross sectional study. STUDY SETTING: Urban slums under Urban Health Centre affiliated to Department of Preventive and Social Medicine, Government Medical College, Nagpur, India. PARTICIPANTS: The study included 1094 all children under 6 y of age, from two randomly selected urban slums. METHODS: Xerophthalmia was diagnosed on the basis of ocular signs and symptoms (WHO recommendations). Dietary intake of vitamin A was assessed by using one year recall method recommended by International Vitamin A Consultative Group. RESULTS: Prevalence of xerophthalmia was estimated to be 8.7%. Nine hundred and ninety-five (90.9%) study subjects were identified as inhabitants consuming dietary vitamin A at below recommended levels. (UPF score < 210). Five hundred and ninety-three (54.2%) study subjects were consuming dietary vitamin A at approximately less than 200 RE/d (UPF score < 120) while 402 (36.2%) were consuming approximately 200-300 RE/d (UPF score 120-210). The prevalence of xerophthalmia was found to be decreasing as the score of usual pattern of food consumption (UPF) increased. CONCLUSIONS: Children with a dietary intake represented by a UPF score of less than 120 were at high risk of developing xerophthalmia, whereas, those consuming vitamin A equal to a UPF score greater than 120 were at comparatively less risk despite being below the recommended levels.     

Effect of some regulators on rat adenohypophyseal cell function in primary monolayer culture

Some features of secretion of labeled somatotrophic hormone (STH) and prolactin in a 5-day monolayer culture of rat adenohypophyses were studied. Hormones were isolated from the culture medium by electrophoresis in polyacrylamide gel. Sodium-dibutyryl cyclic AMP and theophylline stimulated STH and prolactin secretion. Thyrotrophin releasing hormone (TRH) increased the rate of incorporation of L-leucine-¹⁴C into the cell proteins, stimulated prolactin secretion, but did not affect STH liberation. Somatostatin completely inhibited theophylline-induced STH secretion but did not affect prolactin secretion. The characteristics of formation of the labeled STH and prolactin pool in the cells and of the secretion of these hormones into the culture medium are discussed.Laboratory of Biological Standardization of Hormones, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 10, pp. 491–495, October, 1978.     

The vascular effects of different arginase inhibitors in rat isolated aorta and mesenteric arteries

Background and purpose

Arginase and nitric oxide (NO) synthase share the common substrate L-arginine, and arginase inhibition is proposed to increase NO production by increasing intracellular levels of L-arginine. Many different inhibitors are used, and here we have examined the effects of these inhibitors on vascular tissue.

Experimental approach

Each arginase inhibitor was assessed by its effects on isolated rings of aorta and mesenteric arteries from rats by: (i) their ability to preserve the tolerance to repeated applications of the endothelium-dependent agonist acetylcholine (ACh); and (ii) their direct vasorelaxant effect.

Key results

In both vessel types, tolerance (defined as a reduced response upon second application) to ACh was reversed with addition of L-arginine, (S)-(2-boronethyl)-L-cysteine HCl (BEC) or N^G-Hydroxy-L-arginine (L-NOHA). On the other hand, N^ω-hydroxy-nor-L-arginine (nor-NOHA) significantly augmented the response to ACh, an effect that was partially reversed with L-arginine. No effect on tolerance to ACh was observed with L-valine, nor-valine or D,L, α-difluoromethylornithine (DFMO). BEC, L-NOHA and nor-NOHA elicited endothelium-independent vasorelaxation in both endothelium intact and denuded aorta while L-valine, DFMO and nor-valine did not.

Conclusions and implications

BEC and L-NOHA, but not nor-NOHA, L-valine, DFMO or nor-valine, significantly reversed tolerance to ACh possibly conserving L-arginine levels and therefore increasing NO bioavailability. However, both BEC and L-NOHA caused endothelium-independent vasorelaxation in rat aorta, suggesting that these inhibitors have a role beyond arginase inhibition alone. Our data thus questions the interpretation of many studies using these antagonists as specific arginase inhibitors in the vasculature, without verification with other methods.     

细胞色素P450 2C19单碱基突变位点CYP2C19m1的分析

目的:CYP2C19ml是引起CYP2C19酶活性缺陷的主要等位基因,有83％左右的慢代谢者含有CYP2C19ml等位基因,本文试图建立一步PCR测定CYP2C19ml等位基因的方法。方法:根据等位基因特异扩增(ASA)原理设计两对分别特异扩增野生型等位基因和突变型等位基因的引物,建立了一步PCR测定CYP2C19ml等位基因的方法。结果:对39位随机受试者进行了基因分型研究,发现3位CYP2C19ml纯合子、18位CYP2C19ml杂合子,其余18位为野生型纯合子。结论:说明效法能够用于测定CYP2C19ml等住基因,并且证明该法具有简便、快速和污染少的优点。