• 【基于核移植的牛心肌细胞重编程研究隔离。】 复制标题 收藏 收藏
    DOI:10.1089/clo.2006.8.150 复制DOI
    作者列表:Schwarzer M,Carnwath JW,Lucas-Hahn A,Lemme E,Kues WA,Wachsmann B,Haverich A,Martin U,Niemann H
    BACKGROUND & AIMS: :The goal of this study was to establish and validate a protocol for preparing bovine cardiomyocytes from slaughterhouse material for nuclear transfer experiments. The cardiomyocyte was selected because it is a terminally differentiated cell and strongly expresses a unique subset of genes which can be monitored during the reprogramming period. A total of 39 trials were conducted, and an optimized protocol was developed yielding individual contractile cardiomyocytes from 3-5-month-old bovine fetuses The basic protocol involves stabilization of bovine heart tissue for transportation from the slaughterhouse to the laboratory by perfusion with Custodiol. This was followed by an enzymatic dissociation with collagenase in calcium-free medium and yielded individual contractile rod-shaped cardiomyocytes. Subsequent addition of Ca2+ caused the cardiomyocytes to round up which was an essential pre-condition for drawing them into glass transfer pipettes for delivery into the perivitelline space and for efficient electrofusion with cytoplasts derived from in vitro matured bovine oocytes. The use of cardiomyocytes maintained at 37 degrees C in nuclear transfer, resulted in a significantly reduced proportion of blastocysts compared to adult fibroblasts (14.0% versus 32.7%). Storage of cardiomyocytes at 4 degrees C prior to nuclear transfer was not compatible with blastocyst development. It is expected that this system will be valuable for investigating the reprogramming of gene expression which occurs after somatic cell nuclear transfer.
    背景与目标: : 这项研究的目的是建立和验证从屠宰场材料中制备牛心肌细胞以进行核移植实验的协议。选择心肌细胞是因为它是终末分化的细胞,并且强烈表达可以在重编程期间监测的独特基因子集。总共进行了39项试验,并开发了一种优化的方案,从3-5个月大的牛胎儿中产生了单个收缩心肌细胞。基本方案涉及稳定牛心脏组织,以便通过灌注从屠宰场运输到实验室。保管二醇。随后在无钙培养基中与胶原酶酶解离,并产生单个收缩的杆状心肌细胞。随后添加Ca2会导致心肌细胞四舍五入,这是将其吸入玻璃转移移液管以输送到卵黄周围空间以及与来自体外成熟牛卵母细胞的细胞质进行有效电融合的必要前提。与成人成纤维细胞相比,在核转移中使用维持在37 ℃ 的心肌细胞导致胚泡的比例显著降低 (14.0% 对32.7%)。在核转移之前在4摄氏度下储存心肌细胞与胚泡发育不相容。预计该系统对于研究体细胞核移植后发生的基因表达的重编程将很有价值。
  • 【经皮给药颗粒加速的性能研究。】 复制标题 收藏 收藏
    DOI:10.1007/s11517-006-0050-4 复制DOI
    作者列表:Liu Y
    BACKGROUND & AIMS: :We have proposed a transdermal biolistic method to accelerate a powder formulation of drugs to penetrate human skin for the treatment of a range of diseases. One of the key issues for designing and evaluating transdermal biolistic system is ensuing that the powder drugs are delivered into the skin with a controllable velocity range and spatial distribution. The aerodynamics of supersonic nozzles and performance of the delivery system were initially studied, mainly analytically and experimentally. In this paper, computational fluid dynamics is utilized to characterize two existing prototype devices, in order to further investigate the transient gas and particle dynamics in their supersonic nozzles. To validate the implemented numerical approach, calculated pressure histories, two-dimensional flow structures and particle velocity distributions are made and compared with the reported experimental measurements. The key features of gas dynamics, gas-particle interaction and performance of the prototype transdermal biolistics are discussed and interpreted.
    背景与目标: : 我们提出了一种经皮生物注射方法,以加速药物的粉末制剂渗透人体皮肤以治疗一系列疾病。设计和评估透皮生物成像系统的关键问题之一是,将粉末药物以可控的速度范围和空间分布输送到皮肤中。初步研究了超音速喷嘴的空气动力学和输送系统的性能,主要是通过分析和实验进行了研究。本文利用计算流体动力学来表征两个现有的原型设备,以便进一步研究其超音速喷嘴中的瞬态气体和颗粒动力学。为了验证所实施的数值方法,计算了压力历史,二维流动结构和颗粒速度分布,并与报告的实验测量值进行了比较。讨论并解释了气体动力学,气体-颗粒相互作用和原型透皮生物技术性能的关键特征。
  • 【罗非考昔是细胞色素P450 1A2的有效抑制剂: 在健康受试者中使用替扎尼定和咖啡因进行的研究。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2125.2006.02653.x 复制DOI
    作者列表:Backman JT,Karjalainen MJ,Neuvonen M,Laitila J,Neuvonen PJ
    BACKGROUND & AIMS: AIMS:Case reports suggest an interaction between rofecoxib and the CYP1A2 substrate tizanidine. Our objectives were to explore the extent and mechanism of this possible interaction and to determine the CYP1A2 inhibitory potency of rofecoxib. METHODS:In a randomized, double-blind, two-phase cross-over study, nine healthy subjects took 25 mg rofecoxib or placebo daily for 4 days and, on day 4, each ingested 4 mg tizanidine. Plasma concentrations and the urinary excretion of tizanidine, its metabolites (M) and rofecoxib, and pharmacodynamic variables were measured up to 24 h. On day 3, a caffeine test was performed to estimate CYP1A2 activity. RESULTS:Rofecoxib increased the area under the plasma concentration-time curve (AUC(0-infinity)) of tizanidine by 13.6-fold [95% confidence interval (CI) 8.0, 15.6; P < 0.001), peak plasma concentration (C(max)) by 6.1-fold (4.8, 7.3; P < 0.001) and elimination half-life (t(1/2)) from 1.6 to 3.0 h (P < 0.001). Consequently, rofecoxib markedly increased the blood pressure-lowering and sedative effects of tizanidine (P < 0.05). Rofecoxib increased several fold the tizanidine/M-3 and tizanidine/M-4 ratios in plasma and urine and the tizanidine/M-5, tizanidine/M-9 and tizanidine/M-10 ratios in urine (P < 0.05). In addition, it increased the plasma caffeine/paraxanthine ratio by 2.4-fold (95% CI 1.4, 3.4; P = 0.008) and this ratio correlated with the tizanidine/metabolite ratios. Finally, the AUC(0-25) of rofecoxib correlated with the placebo phase caffeine/paraxanthine ratio (r = 0.80, P = 0.01). CONCLUSIONS:Rofecoxib is a potent inhibitor of CYP1A2 and it greatly increases the plasma concentrations and adverse effects of tizanidine. The findings suggest that rofecoxib itself is also metabolized by CYP1A2, raising concerns about interactions between rofecoxib and other CYP1A2 substrate and inhibitor drugs.
    背景与目标:
  • 【单纯性前脑畸形和单纯性低毛丝菌病的连续基因综合征: 与18p11.3缺失有关。】 复制标题 收藏 收藏
    DOI:10.1002/ajmg.a.31386 复制DOI
    作者列表:Kantaputra PN,Limwongse C,Tochareontanaphol C,Mutirangura A,Mevatee U,Praphanphoj V
    BACKGROUND & AIMS: :We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.
    背景与目标: : 我们报告了一名具有独特特征组合的患者,包括小头畸形; 智力低下; 额叶发育不良; 垂体发育不良; 甲状腺功能减退; 普遍脱发; 单个上颌中切牙; 牛角牙症; 正中腭嵴; 纵向开槽的指甲; 和脊柱侧弯。发现他的不平衡核型为45,XY,der(15;18)(q10;q10)。异常星座似乎代表了一个连续的基因综合征,至少部分是由TGIF和负责遗传性低毛丝菌病的基因缺失引起的。我们患者的表型不同于其他报告的del患者 (18p)。可能的解释包括 (1) 不同缺失区域的影响,(2) 由接近的基因引起的位置效应,或 (3) 由染色体易位引起的不同基因的中断。
  • 【躁狂抑郁症与GABRbeta-1基因高度多态性标记之间的遗传关联研究。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1096-8628(19970531)74:3<342::aid-ajm 复制DOI
    作者列表:Puertollano R,Visedo G,Zapata C,Fernández-Piqueras J
    BACKGROUND & AIMS: We report on an association study between a tetranucleotide repeat polymorphism in the GABR beta1 gene and manic-depressive illness in a Spanish population. This gene may be an important candidate for bipolar affective disorders since severe GABergic alterations have been described in patients. Although our results do not reveal a clear evidence for association between manic-depressive illness and GABR beta1, we have found significant differences between patients and controls in the female subpopulation.

    背景与目标: 我们报告了一项西班牙人群中GABR beta1基因的四核苷酸重复多态性与躁狂抑郁症之间的关联研究。该基因可能是双相情感障碍的重要候选者,因为已经在患者中描述了严重的GABergic改变。尽管我们的结果并未揭示出躁狂抑郁症与GABR beta1之间存在关联的明确证据,但我们发现女性亚群的患者与对照组之间存在显着差异。
  • 【通过临床分离株新基因的鉴定和分布研究,揭示了铜绿假单胞菌广泛的基因组可塑性。】 复制标题 收藏 收藏
    DOI:10.1128/IAI.00546-06 复制DOI
    作者列表:Shen K,Sayeed S,Antalis P,Gladitz J,Ahmed A,Dice B,Janto B,Dopico R,Keefe R,Hayes J,Johnson S,Yu S,Ehrlich N,Jocz J,Kropp L,Wong R,Wadowsky RM,Slifkin M,Preston RA,Erdos G,Post JC,Ehrlich GD,Hu FZ
    BACKGROUND & AIMS: :The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.
    背景与目标: : 分布式基因组假说 (DGH) 指出,细菌物种中的每个菌株都从基于群体的上基因组接收到独特的基因分布,该基因分布比任何给定菌株的基因组大很多倍。观察到自然感染种群通常是多克隆的,并且大多数慢性细菌病原体具有高度发达的水平基因转移机制,这表明DGH并提供了手段和机制来解释慢性感染如何在哺乳动物宿主的适应性防御机制中持续存在。先前已经确定了DGH对专性病原体的有效性,我们希望评估其对机会性细菌病原体的适用性。这是通过构建和分析包含约216,000个功能克隆的高度冗余的合并基因组文库来实现的,所述基因组文库是从铜绿假单胞菌的12个低传代临床分离株、6个耳鼻喉科分离株和6个来自其他身体位点构建的。对从该文库中随机挑选的3,214个克隆 (平均插入大小,约1.4 kb) 的序列分析表明,对于铜绿假单胞菌原型菌株pao1的所有基因组序列,348 (10.8%) 的克隆是独特的。这些独特序列中开放阅读框的假设翻译证明了蛋白质与许多细菌毒力因子和其他以前在铜绿假单胞菌中未鉴定的蛋白质的同源性。进行了PCR和基于逆转录PCR的检测,以分析11种临床菌株中这些序列的70个开放阅读框子集的分布和表达模式。这些序列在临床分离株中分布不均匀,近一半 (34/70) 新序列仅存在于单个菌株中的一个或两个中。表达谱分析显示,这些序列中的绝大多数都被表达,这强烈表明它们编码功能蛋白。
  • 【使用口译员的跨文化访谈研究: 系统的文献综述。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2648.2006.03963.x 复制DOI
    作者列表:Wallin AM,Ahlström G
    BACKGROUND & AIMS: AIM:This paper reviews how the interpreter's role is described in empirically based, qualitative cross-cultural interview studies and how trustworthiness is determined. BACKGROUND:Increased immigration during the past decades has created a multiethnic society in many countries. This development poses a challenge to healthcare staff, in that they need to understand how people from different cultures experience health and illness. One way to assess immigrants' experiences is through cross-cultural interview studies, involving an interpreter. Thorough knowledge of the interpreter's role is needed in order to increase the trustworthiness of this kind of nursing research. METHOD:Literature searches were conducted from October to November 2004 using PubMed, CINAHL, Psycinfo, Sociological abstract, Your Journals@ovid, and Eric databases. Qualitative interview studies written in English and performed with an interpreter were included. The Matrix Method was used to review the literature. FINDINGS:In almost all of the 13 relevant papers found, the role of the interpreter(s) in the research process was only sparsely described. In addition, all studies except one employed different techniques to established trustworthiness. The most common techniques were prolonged engagement, member check or triangulation, the latter performed either on the data, investigators or methods. CONCLUSION:Methodological issues with respect to interpreters have received only limited attention in cross-cultural interview studies. Researchers in the field of nursing need to consider (1) the interpreter's role/involvement in the research process; (2) the interpreter's competence and the style of interpreting; (3) the interpreter's impact on the findings. This information is a prerequisite when trying to determine the trustworthiness of a cross-cultural study.
    背景与目标:
  • 【CROPPER: 用于跨平台和跨物种汇编研究的metagene creator资源。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2105-7-418 复制DOI
    作者列表:Paananen J,Storvik M,Wong G
    BACKGROUND & AIMS: BACKGROUND:Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. RESULTS:We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CONCLUSION:CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.
    背景与目标:
  • 【关系质量,激素避孕选择和青少年妇女不使用避孕套的发展关联。】 复制标题 收藏 收藏
    DOI:10.1016/j.jadohealth.2005.12.027 复制DOI
    作者列表:Sayegh MA,Fortenberry JD,Shew M,Orr DP
    BACKGROUND & AIMS: PURPOSE:Consistent condom use is critical to efforts to prevent sexually transmitted infections among adolescents, but condom use may decline as relationships and contraceptive needs change. The purpose of this research is to assess changes in condom non-use longitudinally in the context of changes in relationship quality, coital frequency and hormonal contraceptive choice. METHODS:Participants were women (aged 14-17 years at enrollment) recruited from three urban adolescent medicine clinics. Data were collected at three-month intervals using a face-to-face structured interview. Participants were able to contribute up to 10 interviews, but on average contributed 4.2 interviews over the 27-month period. Independent variables assessed partner-specific relationship quality (five items; scale range 5-25; alpha = .92, e.g., this partner is a very important person to me); and, number of coital events with a specific partner. Additional items assessed experience with oral contraceptive pills (OCP) use and injected depo medroxy-progesterone acetate (DMPA). The outcome variable was number of coital events without condom use during the past three months. Analyses were conducted as a three-level hierarchical linear growth curve model using HLM 6. The Level 1 predictor was time, to test the hypothesis that condom non-use increases over time. Level 2 predictors assessed relationship quality and coital frequency across all partners to assess hypotheses that participants' condom non-use increases over time as a function of relationship quality and coital frequency. Level 3 predictors assessed the participant-level influence of OCP or DMPA experience on time-related changes in condom non-use. RESULTS:A total of 176 women reported 279 sex partners and contributed 478 visits. Both average coital frequency and average condom non-use linearly increased during the 27-month follow-up. At any given follow-up, about 35% reported recent OCP use, and 65% reported DMPA use. HLM analyses showed that condom non-use increased as a function of time (beta = .12; p = .03, Level 1 analysis). Increased condom non-use over time was primarily a function of increased coital frequency (beta = .01; p = .00), although higher levels of relationship quality were associated with increased condom non-use at enrollment (beta = .44; p = .00, Level 2 analysis). The temporal rise in condom non-use significantly increased among DMPA users (beta = .06; p = .00) but not OCP users (Level 3 analysis) (beta = -.04; p = .06). CONCLUSIONS:Developmentally, relationship characteristics and coital frequency appear to have increasing weight in decisions about condom use. Hormonal contraceptive methods are not equivalently associated with the overall temporal decline in condom use. Future research associated with dual contraceptive/condom use should address differential factors associated condom use in combination with different hormonal methods.
    背景与目标:
  • 【残基Leu 93和Asp 96在细菌视紫红质光周期中独立起作用: 对leu 93->Ala,Asp 96->Asn双突变体的研究。】 复制标题 收藏 收藏
    DOI:10.1016/S0006-3495(96)79803-X 复制DOI
    作者列表:Delaney JK,Subramaniam S
    BACKGROUND & AIMS: Previous mutagenesis studies with bacteriorhodopsin have shown that reprotonation of the Schiff's base is the rate-limiting step in the photocycle of the D96N mutant, whereas retinal re-isomerization and return of the protein to the initial state constitute the rate-limiting events in the photocycle of the L93A mutant. Thus, in the D96N mutant, decay of the M intermediate is slowed down by more than 100-fold at pH 7. In the L93A mutant, decay of the O intermediate is slowed down by 250-fold. We report here that in the L93A, D96N double mutant, decay of the M intermediate, as well as the formation and decay of the O intermediate, are slowed down dramatically. The photocycle is completed by the decay of a long-lived O intermediate, as in the L93A mutant. The decay of the M and O intermediates in the double mutant parallels the behavior seen in the single mutants over a wide temperature and pH range, arguing that the observed independence is an intrinsic property of the mutant. The slow decay of the M and O intermediates can be selectively and independently reversed under conditions identical to those used for the corresponding intermediates in the D96N and L93A single mutants. Because the effects of the two individual mutations are preserved in the double mutant and can be independently reversed, we conclude that residues Asp 96 and Leu 93 act independently and at different stages of the bacteriorhodopsin photocycle. These results also show that formation of the O intermediate only requires protonation of the Schiff's base and is independent of the protonation of Asp 96 from the aqueous medium.

    背景与目标: 先前对细菌视紫红质的诱变研究表明,席夫碱的再质子化是D96N突变体光循环中的限速步骤,而视网膜再异构化和蛋白质返回到初始状态则构成了光循环中的限速事件。L93A突变体。因此,在D96N突变体中,M中间体的衰变在ph7下减慢了100倍以上。在L93A突变体中,O中间体的衰变减慢250倍。我们在这里报告说,在L93A,D96N双突变体中,M中间体的衰变以及O中间体的形成和衰变显着减慢。像L93A突变体一样,通过长寿命O中间体的衰变来完成光循环。双突变体中M和O中间体的衰变与在宽温度和pH范围内单个突变体中看到的行为相似,认为观察到的独立性是突变体的内在特性。M和O中间体的缓慢衰变可以在与D96N和L93A单个突变体中相应中间体所使用的条件相同的条件下选择性地和独立地逆转。由于两个个体突变的作用保留在双突变体中并且可以独立逆转,因此我们得出结论,残基Asp 96和Leu 93独立且在细菌视紫红质光循环的不同阶段起作用。这些结果还表明,O中间体的形成仅需要席夫碱的质子化,并且与水性介质中Asp 96的质子化无关。
  • 【神经放射学亚专业专家对脑ct成像研究的重新解释的质量结果。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Jordan MJ,Lightfoote JB,Jordan JE
    BACKGROUND & AIMS: PURPOSE:To determine the clinical importance and relative value of reinterpreting brain CT imaging studies by subspecialty experts regarding changes in clinical management. METHODS:Computerized records were queried at two institutions during the years 2002-2003 for both primary interpretation by board-certified nonneuroradiologists and secondary interpretation by three neuroradiologists. A total of 1,081 cases were reviewed. Each case was initially interpreted as an emergent or urgent study. The reinterpreted studies were scored as concordant or discordant by the subspecialty experts. The discordant studies were then categorized as a "major discordance" if there was a change in clinical management, or as a "minor discordance" if there was no impact or change in clinical management. RESULTS:Of the 1,081 studies reviewed, 14 studies were identified as discordant (1.3%). Of those discordant studies, four were categorized as major discrepancies necessitating a change in clinical management (0.4 %). Ten were categorized as minor discrepancies (0.9%). There were no permanent adverse outcomes with respect to morbidity and mortality as a result of any discrepancy. CONCLUSION:The vast majority of interpreted head CT cases read by board-certified general radiologists do not result in discordant interpretations as verified by subspecialty experts. Discordant interpretations did not result in changes in clinical management in most cases. Double reading of head CTs by subspecialty experts appears to be an inefficient method of substantially improving imaging health quality outcomes.
    背景与目标:
  • 【正常年轻和老年妇女肠道维生素d受体,钙吸收和血清1,25二羟基维生素d之间的关系。】 复制标题 收藏 收藏
    DOI:10.1359/jbmr.1997.12.6.922 复制DOI
    作者列表:Kinyamu HK,Gallagher JC,Prahl JM,DeLuca HF,Petranick KM,Lanspa SJ
    BACKGROUND & AIMS: The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty-nine young women age 25-35 years were compared with 41 elderly women age 65-83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25-hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12-30% of the variance in the age-related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.

    背景与目标: 随着年龄的增长,肠道钙吸收减少的确切机制尚不清楚。血清1,25-二羟基维生素d (1,25(OH)2D) 随着年龄的增长而降低或肠道维生素d受体 (VDR) 蛋白浓度降低是可能的原因。这项研究的目的是检查年龄对这些因素的影响。将59名年龄在25-35岁之间的年轻女性与41名年龄在65-83岁之间的老年女性进行了比较,这些女性接受了VDR,使用20 mg和100 mg钙载体的钙吸收以及钙促激素的测量。与年轻女性相比,老年女性两种测试对钙的吸收均较低 (p <0.05)。血清1,25(OH)2D和十二指肠VDR蛋白浓度在两个年龄组之间没有显着差异。血清1,25(OH)2D与青年 (r = 0.35,p <0.007) 和老年妇女 (r = 0.58,p <0.0001) 的20 mg钙吸收试验相关,与老年人的100 mg钙吸收相关 (r = 0.32; p <0.05)。VDR与年轻女性或老年女性的钙吸收无关,也与血清1,25(OH)2D和血清25-羟基维生素d无关。总而言之,钙吸收的减少不能用肠道VDR的减少来解释。血清1,25(OH)2D与两种钙吸收测试之间的相关性仅占钙吸收测试中年龄相关变化的12-30%。其他尚未了解的因素是钙吸收随年龄下降的原因。
  • 【I型糖尿病易感性候选基因的分析: 2q31-35染色体上基因的病例对照和家庭关联研究。】 复制标题 收藏 收藏
    DOI:10.2337/diab.46.6.1069 复制DOI
    作者列表:Owerbach D,Naya FJ,Tsai MJ,Allander SV,Powell DR,Gabbay KH
    BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

    背景与目标: 最近的基因组搜索表明,许多基因座与I型糖尿病易感性之间存在推定的联系。据报道,染色体2q31-35区域与I型糖尿病的易感性有关,并被认为包含多个糖尿病易感性位点。这些候选基因包括HOXD基因簇,BETA2,CTLA4,CD28,IGFBP2和igfbp5。需要在人群和家庭中进行关联研究,以确认和/或确定实际的易感性位点。我们在此报告了HOXD8,BETA2和IGFBP5的几个先前未知的DNA多态性,我们将其与先前已知的HOXD8和CTLA4的多态性一起使用,以测试这些候选基因座是否是染色体2q31-35上的易感基因。使用病例对照设计和随后的家庭关联方法来确认关联,我们没有发现证据表明这些候选基因与I型糖尿病的易感性有关。
  • 【神经性厌食症的全基因组关联研究表明,与瘦素信号失调有关的风险位点。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-01674-8 复制DOI
    作者列表:
    BACKGROUND & AIMS: :We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.
    背景与目标: : 我们使用严格定义的表型对神经性厌食症 (AN) 进行了全基因组关联研究 (gwa)。表型变异性的分析导致鉴定出一种特定的遗传危险因素,该因素具有全基因组意义 (EBF1中的rs929626 (早期b细胞因子1); P   =   2.04  ×   10-7; Or   =   0.7; 95% 置信区间 (CI)  =   0.61-0.8) 与独立复制 (p   =   0.04),提示一个变异介导的瘦素信号失调可能在AN中起作用。具有变体的LD中的多个snp支持名义上的关联。这表明,尽管AN的临床和病因学异质性已得到普遍认可,但对病例的进一步仔细分类可能会提供更精确的基因组信号。在这项研究中,通过改进AN的表型谱,我们提出了名义上与AN相关的可复制gwa信号,突出了潜在的重要候选基因座,以供进一步研究。
  • 【在急诊科新发癫痫发作患者中进行实验室研究的实用性。】 复制标题 收藏 收藏
    DOI:10.1016/s0196-0644(05)82337-6 复制DOI
    作者列表:Turnbull TL,Vanden Hoek TL,Howes DS,Eisner RF
    BACKGROUND & AIMS: :Extensive laboratory testing is often performed in the emergency department evaluation of the new-onset seizure patient. To determine the utility of such testing, a prospective study of patients with a new-onset seizure presenting to the ED of an inner-city, university-affiliated teaching hospital was done. One hundred thirty-six patients were entered into the study between October 1984 and January 1988. All patients had uniform data collection performed. Pertinent historical information and physical examination findings were recorded on a standardized form before laboratory abnormality was a sole or contributory cause of the seizure disorder. These included four patients with hypoglycemia, four with hyperglycemia, two with hypocalcemia, and one with hypomagnesemia. Only two cases (hypoglycemia) were not suspected on the basis of findings on the history or physical examination. In ED patients, the incidence of a new-onset seizure due to a correctable metabolic disturbance is low. We conclude that, with the exception of the serum glucose, the extensive ED laboratory workup often done for the evaluation of a new-onset seizure is unnecessary. Further test ordering should be directed by the medical history and physical examination.
    背景与目标: : 在急诊科对新发癫痫患者的评估中,经常进行广泛的实验室测试。为了确定这种测试的实用性,对向市中心大学附属教学医院的ED呈递的新发癫痫发作患者进行了前瞻性研究。在1984年10月和1988年1月之间,有136名患者进入了研究。所有患者均进行了统一的数据收集。在实验室异常是癫痫发作的唯一或促成原因之前,将相关的历史信息和体格检查结果记录在标准化表格上。其中包括4名低血糖患者,4名高血糖患者,2名低钙血症患者和1名低镁血症患者。根据病史或体格检查发现,仅怀疑有2例 (低血糖)。在ED患者中,由于可纠正的代谢紊乱而引起的新发癫痫发作的发生率较低。我们得出的结论是,除血清葡萄糖外,通常不需要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的检查顺序应由病史和体格检查指示。

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