• 【哪些血栓形成基因突变是复发性流产的危险因素?】 复制标题 收藏 收藏
    DOI:10.1111/j.1600-0897.2006.00419.x 复制DOI
    作者列表:Goodman CS,Coulam CB,Jeyendran RS,Acosta VA,Roussev R
    BACKGROUND & AIMS: PROBLEM:Thrombophilia has been associated with poor obstetrical outcomes. To determine the association of specific inherited thrombophilias and recurrent pregnancy loss, 10 thrombophilic genes were investigated. METHOD OF STUDY:A total of 550 women with a history of recurrent pregnancy loss had buccal swabs taken for DNA analyses of the following gene mutations: factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C. The frequencies of these mutations were compared with controls published in the literature. RESULTS:When examined individually, PAI-1 4G/5G (P = 0.009), factor XIII V34L (P < 0.0001), and homozygous MTHFR C667T (P < 0.0001) correlated significantly with recurrent pregnancy loss compared with controls. The frequency of the factor V Y1702C mutation was extremely low in patients and controls; thus, this gene was removed from further calculations. The remaining six mutated genes, when analyzed cumulatively, also corresponded with recurrent pregnancy loss (P < 0.0001). CONCLUSION:A panel of thrombogenic gene mutations consisting of factor V G1691A, factor V H1299R (R2), factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), MTHFR C677T, and MTHFR A1298C can identify individuals at risk for recurrent pregnancy loss.
    背景与目标: 问题:血友病与产科预后不良有关。为了确定特定遗传性血栓形成症与复发性流产的关联,研究了10个血栓形成性基因。
    研究方法:总共550名有反复性流产史的妇女接受了口腔拭子以进行以下基因突变的DNA分析:因子V G1691A,因子V H1299R(R2),因子V Y1702C,因子II凝血酶原G20210A,因子XIII V34L,β-纤维蛋白原-455G> A,PAI-1 4G / 5G,HPA1a / b(L33P),亚甲基四氢叶酸还原酶(MTHFR)C677T,MTHFR A1298C。将这些突变的频率与文献中发表的对照进行了比较。
    结果:当单独检查时,与对照组相比,PAI-1 4G / 5G(P = 0.009),XIII因子V34L(P <0.0001)和纯合MTHFR C667T(P <0.0001)与复发性流产显着相关。在患者和对照组中,V Y1702C因子突变的频率非常低。因此,该基因已从进一步的计算中删除。当进行累积分析时,剩下的六个突变基因也与复发性流产相对应(P <0.0001)。
    结论:一组血栓形成基因突变,由因子V G1691A,因子V H1299R(R2),因子II凝血酶原G20210A,因子XIII V34L,β-纤维蛋白原-455G> A,PAI-1 4G / 5G,HPA1 a / b( L33P),MTHFR C677T和MTHFR A1298C可以识别有复发性流产风险的个体。
  • 【大鼠角膜缘和中央角膜上皮中基因表达(SAGE)的系列分析。】 复制标题 收藏 收藏
    DOI:10.1167/iovs.06-0216 复制DOI
    作者列表:Adachi W,Ulanovsky H,Li Y,Norman B,Davis J,Piatigorsky J
    BACKGROUND & AIMS: PURPOSE:To identify genes preferentially expressed in the stem-cell-rich limbal epithelium of the rat cornea. METHODS:The limbal and central corneal epithelial cells of 6-week-old rats were isolated by microdissection. Serial analysis of gene expression (SAGE) libraries were constructed and analyzed, and in situ hybridization, reverse transcription-polymerase chain reaction (RT-PCR) and cDNA cloning were conducted by conventional procedures. RESULTS:The rat limbal and central corneal epithelial SAGE libraries consisted of 41,894 and 40,691 tags, respectively. After annotation, this was reduced to 759 transcripts specific for the limbal library and 844 transcripts specific for the central corneal library; 2292 transcripts overlapped. Transcripts encoding proteins with metabolic functions comprised the major functional category in both libraries. In situ hybridization and/or RT-PCR results of 12 of the most abundant, highly enriched transcripts in the limbal epithelium were in general agreement with the SAGE data and showed that these proteins are also expressed in the conjunctival epithelium. Interesting limbal-enriched transcripts encode WDNM1-like protein (similar to WDNM1/Expi, a putative secreted proteinase and inhibitor of metastasis), mesothelin (a cancer marker), marapsin (a trypsin-like serine protease that may control cell growth and migration), K4 and K15 (both cytokeratins), and membrane-spanning four-domain subfamily A member 8B. WDNM1-like protein was cloned and confirmed as a member of the four-disulfide core family. CONCLUSIONS:The SAGE results extend the database of genes expressed in the rodent cornea and suggest an association between several genes preferentially expressed in the limbal epithelium with cellular proliferation and migration.
    背景与目标: 目的:鉴定在大鼠角膜的富含干细胞的角膜缘上皮细胞中优先表达的基因。
    方法:采用显微解剖技术分离6周龄大鼠角膜缘和角膜上皮细胞。构建并分析基因表达(SAGE)库的序列分析,并通过常规方法进行原位杂交,逆转录-聚合酶链反应(RT-PCR)和cDNA克隆。
    结果:大鼠角膜缘和角膜上皮SAGE文库分别由41,894和40,691个标签组成。注释后,该数目减少为角膜缘文库特异的759个转录物和中央角膜文库特异的844个转录物。 2292个成绩单重叠。编码具有代谢功能的蛋白质的转录本在两个文库中均属于主要功能类别。角膜缘上皮细胞中12种最丰富,高度富集的转录本的原位杂交和/或RT-PCR结果与SAGE数据基本一致,表明这些蛋白也在结膜上皮细胞中表达。有趣的角膜缘丰富的转录本编码WDNM1样蛋白(类似于WDNM1 / Expi,一种推测的分泌蛋白酶和转移抑制剂),间皮素(一种癌症标志物),marapsin(一种胰蛋白酶样丝氨酸蛋白酶,可以控制细胞的生长和迁移)。 ,K4和K15(均为细胞角蛋白)和跨膜四结构域亚家族A成员8B。克隆了类似WDNM1的蛋白质,并确认其为四-二硫键核心家族的成员。
    结论:SAGE结果扩展了在啮齿动物角膜中表达的基因数据库,并暗示了在角膜缘上皮中优先表达的几个基因与细胞增殖和迁移之间的关联。
  • 【与人神经胶质瘤有关的人核糖体蛋白L14.22的全长新基因。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Qi ZY,Hui GZ,Li Y,Zhou ZX,Gu SH,Xie Y
    BACKGROUND & AIMS: BACKGROUND:This study was undertaken to obtain differentially expressed genes related to human glioma by cDNA microarray and the characterization of a novel full-length gene. METHODS:Total RNA was extracted form human glioma and normal brain tissue, and mRNA was used as a probe. The results of hybridization procedure were scanned with the computer system. The gene named 507E08 cone was subsequently analyzed by northern blot, bioinformatic approach, and protein expression. RESULTS:Fifteen differentially expressed genes were obtained from human glioma by hybridization and scanning for four times. Northern blot analysis confirmed that the 507E08 clone was low expressed in human brain tissue and over expressed in human glioma tissues. The analysis of BLASTn and BLASTx showed that the 507E08 clone was a novel full-length gene, which codes 203 amino acid of protein and is called human ribosomal protein 14.22 gene. The nucleotide sequence had been submitted to the GenBank with the accession number of AF329277. After expression in E. coli., protein yielded a major band of apparent molecular mass 22 kDa on an SDS-PAGE gel. CONCLUSIONS:cDNA microarray technology can be successfully used to identify differentially expressed genes. The novel full-length gene of human ribosomal protein 13.22 may be correlated with the development of human glioma.
    背景与目标: 背景:本研究旨在通过cDNA微阵列技术获得与人神经胶质瘤相关的差异表达基因,并鉴定一个新的全长基因。
    方法:从人脑胶质瘤和正常脑组织中提取总RNA,并以mRNA为探针。杂交程序的结果用计算机系统扫描。随后通过Northern印迹,生物信息学方法和蛋白质表达来分析名为507E08视锥细胞的基因。
    结果:通过杂交和扫描4次,从人脑胶质瘤中获得了15个差异表达基因。 Northern印迹分析证实507E08克隆在人脑组织中低表达而在人脑胶质瘤组织中高表达。对BLASTn和BLASTx的分析表明,507E08克隆是一个新颖的全长基因,其编码蛋白质的203个氨基酸,被称为人核糖体蛋白质14.22基因。该核苷酸序列已提交给GenBank,登录号为AF329277。在大肠杆菌中表达后,蛋白质在SDS-PAGE凝胶上产生一条表观分子量为22 kDa的主带。
    结论:cDNA微阵列技术可成功用于鉴定差异表达的基因。人核糖体蛋白13.22的新的全长基因可能与人脑胶质瘤的发展有关。
  • 【罕见的母体mRNA编码调控蛋白,这些蛋白控制着海胆胚胎中谱系特异性基因的表达。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.20.7953 复制DOI
    作者列表:Cutting AE,Höög C,Calzone FJ,Britten RJ,Davidson EH
    BACKGROUND & AIMS: :The prevalence of mRNAs coding for the sea urchin embryo regulatory factors P3A1 and P3A2 was measured by single-strand probe excess solution hybridization. P3A1 and P3A2 are not homologous proteins, though they both bind specifically to a particular cis-regulatory sequence. Interaction at this target site is known to be required for lineage-specific expression of an aboral ectoderm-specific gene and probably for several other genes as well. Genome blot hybridizations show that both factors are encoded by single-copy genes. Maternal mRNAs for both factors are present at less than 10(3) molecules per egg, which places them in the rare mRNA class. During development to the mesenchyme blastula stage, the amount of P3A1 mRNA (per embryo) increases severalfold while that of P3A2 remains approximately constant. Specification of the aboral ectoderm founder cells and of their initial patterns of gene expression must occur during early to mid-cleavage stage. Therefore, the regulatory proteins needed for this process must be produced by this stage. We show that the quantities of the P3A proteins that can be synthesized from the numbers of mRNA molecules present in the large blastomeres of the early embryo are sufficient to be functional, because these proteins will be accumulated in the nuclei. Thus maternal P3A1 or P3A2 proteins asre not required, nor were these detected in earlier studies. Furthermore, differential spatial (as well as temporal) distribution of both of these newly synthesized factor species could result from the unequal cleavage pattern utilized in the sea urchin egg.
    背景与目标: :通过单链探针过量溶液杂交测量编码海胆胚胎调节因子P3A1和P3A2的mRNA的发生率。尽管P3A1和P3A2都与特定的顺式调控序列特异性结合,但它们不是同源蛋白。已知该靶标位点的相互作用是特定于宗族的外胚层特异性基因的谱系表达所必需的,并且可能还需要其他几个基因。基因组印迹杂交显示这两个因子均由单拷贝基因编码。每个鸡蛋的母体mRNA均少于10(3)个分子,这使它们处于罕见的mRNA类中。在发育到间充质囊阶段期间,P3A1 mRNA(每个胚胎)的数量增加了几倍,而P3A2的数量则保持大致恒定。胎盘外胚层基础细胞及其基因表达的初始模式的规范必须在卵裂早期至中期进行。因此,必须在该阶段生产该过程所需的调节蛋白。我们表明,可以从早期胚胎的大型卵裂球中存在的mRNA分子数量合成的P3A蛋白数量足以发挥功能,因为这些蛋白将积聚在细胞核中。因此,不需要母体P3A1或P3A2蛋白,也不需要在早期研究中检测到这些蛋白。此外,这两种新合成的因子物种在空间(以及时间)上的差异分布可能是由于海胆卵中使用的不均等卵裂模式造成的。
  • 【体外药物活性和药代动力学在预测抗分枝杆菌疗法有效性中的价值:一项重要综述。】 复制标题 收藏 收藏
    DOI:10.1097/00000441-199706000-00008 复制DOI
    作者列表:Burman WJ
    BACKGROUND & AIMS: Marked increases in case rates of drug-resistant tuberculosis and nontuberculous mycobacterial infections have brought renewed urgency to the development of new treatment regimens for mycobacterial infections. Preclinical data, such as in vitro measures of drug activity and pharmacokinetics, are used in the design of new treatment regimens. This review surveys the extensive published clinical experience concerning the treatment of drug-susceptible tuberculosis to evaluate the use of these preclinical measures in predicting clinical outcomes of antimycobacterial therapy. In vitro measures of drug activity predict the potency of a drug to prevent the emergence of resistance to other antimycobacterial drugs but do not predict the sterilizing activity of a drug or the activity of drug combinations. In vitro measures of drug activity do not allow reliable predictions of the level at which an organism should be considered resistant. Assays of drug penetration in tissues and activity against intracellular bacilli add modestly to the predictive value of in vitro measures of drug activity but still do not predict sterilizing activity. In contrast, animal models of tuberculosis have predicted relative drug potency (including sterilizing activity), the efficacy of multidrug regimens, and the duration of therapy needed. Despite pharmacokinetic parameters that would suggest the need for multiple doses per day, all of the first-line antituberculous drugs are active when given as infrequently as twice weekly. It is difficult to predict the efficacy of therapy for an intracellular pathogen that has the capacity for dormancy. Better in vitro models are needed, particularly ones that predict sterilizing activity.

    背景与目标: 耐药结核病和非结核分枝杆菌感染的病例率显着增加,这为开发针对分枝杆菌感染的新治疗方案带来了新的紧迫性。临床前数据,例如药物活性和药代动力学的体外测量,用于设计新的治疗方案。这篇综述调查了有关药物敏感性肺结核治疗的广泛发表的临床经验,以评估这些临床前措施在预测抗分枝杆菌治疗的临床结果中的应用。药物活性的体外量度可以预测药物对其他抗分枝杆菌药物产生抗药性的能力,但不能预测药物的灭菌活性或药物组合的活性。药物活性的体外测量不能可靠地预测应将生物体视为抗药性的水平。药物在组织中的渗透和针对细胞内细菌的活性的测定适度地增加了药物活性体外测量的预测价值,但仍不能预测灭菌活性。相反,结核病的动物模型预测了相对的药效(包括杀菌活性),多种药物疗法的疗效以及所需的治疗时间。尽管药代动力学参数表明每天需要多剂量,但每隔一周两次不频繁使用时,所有一线抗结核药物均具有活性。难以预测具有休眠能力的细胞内病原体的治疗效果。需要更好的体外模型,尤其是预测杀菌活性的模型。

  • 【肺鱼是化石吗?阿片/孤儿蛋白基因家族进化的观察。】 复制标题 收藏 收藏
    DOI:10.1016/j.ygcen.2006.07.010 复制DOI
    作者列表:Lee J,Alrubaian J,Dores RM
    BACKGROUND & AIMS: :This minireview considers the possibility that there is a correlation between the slow rate of morphological change and speciation events that has been occurred within the lungfish lineage since the Permian period, and the apparent slow rate of divergence in the amino acid sequences of lungfish opioid precursor sequences. The status of lungfish as "living fossils" is considered.
    背景与目标: :本篇小型综述认为,二叠纪以来在肺鱼谱系内发生的形态变化和物种形成的缓慢速率与形态上的缓慢变化与肺鱼阿片样物质前体的氨基酸序列的明显缓慢速率之间存在相关性的可能性序列。考虑到肺鱼作为“活化石”的地位。
  • 【肿瘤进展-差异治疗的目标。】 复制标题 收藏 收藏
    DOI:10.1002/jcp.20728 复制DOI
    作者列表:Pardee AB
    BACKGROUND & AIMS: :Differential killing of the patient's cancer cells versus normal cells is a necessity for chemotherapy. Advantage can be taken of close regulations of gene expression and of enzyme activity that are essential for normal cell functioning, and that are altered during tumor progression. Summarized here is our research on four such progression changes of cancer cells; some deregulate proliferation control and others decrease programmed death (apoptosis). These processes will be illustrated with examples of potential chemotherapies based on them. Methods for discovery of such changes include Differential Display and microarrays.
    背景与目标: :与正常细胞相比,不同程度地杀死患者的癌细胞是化疗的必要条件。可以利用基因表达和酶活性的紧密调节,这些调节对于正常的细胞功能是必不可少的,并且在肿瘤进展过程中会改变。这里总结了我们对癌细胞的四个这样的进展变化的研究。一些人放松了对增殖的控制,而另一些人减少了程序性死亡(细胞凋亡)。这些过程将以基于它们的潜在化学疗法为例进行说明。发现这种变化的方法包括差异显示和微阵列。
  • 【全脑原发性和单发性下垂病的连续基因综合征:与18p11.3缺失相关。】 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: :我们报告的患者具有独特的功能组合,包括小头畸形;智力低下;额叶发育不良;垂体发育不全甲状腺功能减退;普遍性脱发;单上颌中切牙;牛头牙症pa中纵向开槽的指甲;和脊柱侧弯。发现他的不平衡核型为45,XY,der(15; 18)(q10; q10)。异常群似乎代表着一种连续的基因综合征,这种综合征至少部分地是由于TGIF的缺失和负责遗传性单纯性遗传不足的基因引起的。我们患者的表型与其他报道的del(18p)患者不同。可能的解释包括(1)不同缺失区域的作用,(2)由附近基因引起的位置作用,或(3)由染色体易位引起的不同基因的中断。
  • 【当代心肌梗塞溶栓治疗后出血的发生率和预测因素。闭塞性冠状动脉(GUSTO)I研究者的链激酶和组织纤溶酶原激活剂的全球利用。】 复制标题 收藏 收藏
    DOI:10.1161/01.cir.95.11.2508 复制DOI
    作者列表:Berkowitz SD,Granger CB,Pieper KS,Lee KL,Gore JM,Simoons M,Armstrong PW,Topol EJ,Califf RM
    BACKGROUND & AIMS: BACKGROUND:Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials.

    METHODS AND RESULTS:We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).

    CONCLUSIONS:Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

    背景与目标: 背景:尽管溶​​栓治疗在降低急性心肌梗死死亡率方面的益处已得到广泛认可,但在大型试验中对出血的类型和出血的危险因素的描述却较少。

    < strong>方法和结果:我们在GUSTO-I急性心肌梗塞试验的GUSTO-I试验中,对41,021例患者的基线特征,结局和出血发生率进行了分析,包括其位置,严重程度和治疗方案。在有完整数据的40,903名患者中,有1.2%出现严重出血,11.4%的患者在不同部位出现中度出血。最常见的出血来源与手术有关。溶栓方案与出血发生率密切相关。链激酶加静脉肝素,链激酶和组织纤溶酶原激活剂加肝素联合治疗的出血量相对较多。在多变量分析中,出血的四个最有力的独立预测因子是年龄大,体重轻,女性和非洲血统。当对未进行侵入性治疗的患者进行多变量分析时,它们仍然是出血的最重要预测指标。严重出血的存在与其他不良后果(复发事件,左心室功能障碍,心律不齐或中风)相关。

    结论:该人群出血的重要预测因素是年龄增加,体重减轻,女性性别,非洲血统和经历侵入性程序。其他非出血性不良临床预后与中度和重度出血有关,这又与住院天数的延长和30天病死率有关。

  • 【躁狂抑郁症与来自GABRbeta-1基因的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GABR beta1基因中的四核苷酸重复多态性与西班牙人群的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,因为已在患者中描述了严重的GAB能改变。尽管我们的结果并未显示出躁狂抑郁症与GABR beta1之间存在关联的明确证据,但我们发现女性亚人群中的患者与对照组之间存在显着差异。

  • 【接受腹膜内光动力疗法的患者的肿瘤和正常组织中的光敏蛋白摄取。】 复制标题 收藏 收藏
    DOI:10.1158/1078-0432.CCR-06-0953 复制DOI
    作者列表:Hahn SM,Putt ME,Metz J,Shin DB,Rickter E,Menon C,Smith D,Glatstein E,Fraker DL,Busch TM
    BACKGROUND & AIMS: PURPOSE:A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. EXPERIMENTAL DESIGN:Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. RESULTS:Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (
    背景与目标: 目的:Photofrin介导的i.p.的II期临床试验。以前的报告中显示的光动力疗法疗效有限,且具有明显的急性但非慢性毒性。该试验和本报告主题的第二个目的是确定肿瘤和正常组织中的光敏蛋白摄取量。
    实验设计:患者在减容手术前48小时接受静脉注射2.5 mg / kg的Photofrin。通过分光光度法对从肿瘤和手术中切除的正常组织中提取的药物进行分光光度法分析来测量光蛋白的摄取。使用混合效应模型从统计学上考虑了这些组织之间的药物吸收差异。
    结果:在从该试验的100名患者中的58名患者中收集的301个样品中测量了光敏蛋白的浓度。在正常组织中,药物吸收显着不同(P <0.0001),是七种不同组织类型的函数。在肠道毒性限制组织中,全厚度大肠和小肠中基于模型的平均(SE)Photofrin水平分别为2.70 ng / mg(0.32 ng / mg)和3.42 ng / mg(0.24 ng / mg),分别。在肿瘤中,药物吸收随患者队列的不同而有显着差异(P = 0.0015):卵巢癌,胃癌或小肠癌患者中基于模型的平均Photofrin水平为3.32至5.31 ng / mg。肉瘤,阑尾或结肠癌患者中2.09至2.45 ng / mg;假性粘液瘤患者为0.93 ng / mg。卵巢癌,胃癌和小肠癌的Photofrin摄取明显高于全厚度的大肠和/或小肠。然而,肿瘤与肠道中平均药物水平的比率是中等的(<或= 2.31)。
    结论:在肿瘤与腹膜腔正常组织之间的光敏蛋白摄取中发现了一些选择性,但是相对于毒性受限的正常组织(肠)而言,药物摄取的绝对差异很小。先前已经报道过,药物选择性的这种狭窄差异可能导致治疗应用中的狭窄窗口。
  • 【在空肠弯曲杆菌感染的鸡中口服抗体预防和治疗。】 复制标题 收藏 收藏
    DOI:10.1046/j.1365-2249.1997.3901288.x 复制DOI
    作者列表:Tsubokura K,Berndtson E,Bogstedt A,Kaijser B,Kim M,Ozeki M,Hammarström L
    BACKGROUND & AIMS: :Passive immunity against gastrointestinal infections has recently been successfully applied as prophylaxis and therapy in patients in a variety of virally and bacterially induced infections. Campylobacter jejuni is frequently associated with acute diarrhoea in humans, and several species of animals have been shown to transmit the disease, although birds have been implicated as the main source of infection. We used bovine and chicken immunoglobulin preparations from the milk and eggs, respectively, of immunized animals for prophylactic and therapeutic treatment of chickens infected with C. jejuni. A marked prophylactic effect (a >99% decrease in the number of bacteria) was noted using either antibody preparation, whereas the therapeutic efficacy, i.e. when antibodies were given after the infection was established, was distinctly lower (80-95%) as judged by faecal bacterial counts. These observations may serve as a starting point for experiments aimed at elimination of the infection in an industrial or farm setting. It may also encourage future attempts to treat, prophylactically or therapeutically, patients with Campylobacter-induced diarrhoea.
    背景与目标: :最近,针对胃肠道感染的被动免疫已成功应用于各种病毒和细菌引起的感染的预防和治疗中。空肠弯曲菌常与人类急性腹泻有关,尽管鸟类被认为是主要的感染源,但已显示出几种动物可传播这种疾病。我们分别使用免疫动物的牛奶和鸡蛋中的牛和鸡免疫球蛋白制剂对空肠弯曲杆菌感染的鸡进行预防和治疗。两种抗体制剂均具有显着的预防作用(细菌数量减少> 99%),而判断的治疗效果(即在感染确定后给予抗体)则明显较低(80-95%)通过粪便细菌计数。这些观察结果可作为旨在消除工业或农场感染的实验的起点。它还可能鼓励将来尝试预防性或治疗性弯曲杆菌引起的腹泻患者。
  • 【接受高活性抗逆转录病毒疗法治疗的替诺福韦富马酸二甲氧呋酯(TDF)暴露和TDF未暴露的HIV感染门诊患者的低血磷评估。】 复制标题 收藏 收藏
    DOI:10.1111/j.1468-1293.2006.00407.x 复制DOI
    作者列表:Buchacz K,Brooks JT,Tong T,Moorman AC,Baker RK,Holmberg SD,Greenberg A,HIV Outpatient Study (HOPS) Investigators.
    BACKGROUND & AIMS: OBJECTIVES:Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS). METHODS:We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n = 165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF-) group; n = 90], and who had normal baseline phosphate and creatinine values. RESULTS:The TDF+ and TDF- groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P = 0.18) and number of phosphate measurements (median = 3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF-patients developed grade 2 hypophosphataemia (2.0-2.4 mg/dL), and 2.4% of TDF+ patients vs 0% of TDF-patients developed grade 3 hypophosphataemia (1.0-1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+ patients vs 8.0 per 100 person-years among TDF-patients (P = 0.11). CONCLUSIONS:The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia.
    背景与目标: 目的:已经报道了接受替诺福韦二富马酸富马酸酯(TDF)感染HIV的患者发生低血磷的情况(通常与肾功能不全同时发生),但基线肾功能正常的HIV感染者的随机安慰剂对照试验发现TDF和安慰剂组的低磷血症。我们在HIV门诊研究(HOPS)中评估了2级和更高的低血磷的发生率。
    方法:我们分析了开始采用含TDF的高活性抗逆转录病毒疗法(HAART)方案[TDF暴露(TDF)组)的患者的前瞻性队列研究。 n = 165]或保留TDF的HAART方案[未暴露TDF(TDF-)的组; n = 90],并且基线磷酸盐和肌酐值正常。
    结果:TDF和TDF-组的中位随访时间(分别为10.9和8.8个月; P = 0.18)和磷酸盐测量次数(两者的中位数= 3)具有可比性,并且在大多数临床和人口统计学因素上相似。在随访期间,TDF的12.7%与TDF的患者的6.7%发生了2级低血磷(2.0-2.4 mg / dL),TDF的2.4%vs TDF的患者中出现了3级的低血磷(1.0-1.9 mg) / dL);没有一个发生4级低血磷(<1.0 mg / dL)。 TDF患者中2级或更高水平低血磷的发生率为每100人年16.7人,而TDF患者为每100人年8.0人(P = 0.11)。
    结论:在观察的头1至2年中,与含TDF的HAART的HOPS患者相比,接受含TDF的HAART的HOPS患者的低磷酸盐血症发生率有所升高,但差异无统计学意义。需要对更大的人群进行更长时间的随访,以确定这种联系趋势是否达到统计学意义并评估低血磷的临床后果。
  • 【使用CT,EUS和FDG-PET进行新辅助治疗的反应监测。】 复制标题 收藏 收藏
    DOI:10.1016/j.bpg.2006.04.004 复制DOI
    作者列表:Sloof GW
    BACKGROUND & AIMS: :Neoadjuvant or adjuvant multimodality therapy in oesophageal cancer is introduced in an effort to improve prognosis. However, in a substantial fraction of patients there is no response to this non-surgical therapy. Non-invasive imaging modalities such as computed tomography (CT), endoscopic ultrasound (EUS) and 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) have been evaluated for assessing patient response to therapy, and these are described in this review. Currently, FDG-PET seems to be the best available tool for neoadjuvant therapy response assessment in oesophageal cancer.
    背景与目标: :在食管癌中引入新辅助或辅助多模治疗以改善预后。但是,在相当一部分患者中,对这种非手术疗法没有任何反应。已评估了计算机断层扫描(CT),内窥镜超声(EUS)和18F-2-氟-2-脱氧-d-葡萄糖正电子发射断层扫描(FDG-PET)等非侵入性成像方式,以评估患者对治疗的反应,并在这篇评论中对此进行了描述。目前,FDG-PET似乎是食管癌新辅助治疗反应评估的最佳可用工具。
  • 【拟南芥中吸收氢酶的调控和氢利用对基因表达的影响。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00381-06 复制DOI
    作者列表:Rey FE,Oda Y,Harwood CS
    BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.
    背景与目标: :Rhodopseudomonas palustris是一种紫色的兼性光养细菌,它利用氢气作为电子供体,在光养植物生长过程中固定二氧化碳,或在固氮过程中合成氨气。它还使用氢作为电子补充剂,以在光异养生长期间将氧化的碳化合物(例如苹果酸)完全同化到细胞材料中。 R. palustris基因组预测膜结合的镍铁摄取氢化酶和几种调节蛋白来控制氢化酶的合成。与氢化酶基因簇直接相邻的还有一个新的传感器激酶基因(RPA0981)。在这里,我们显示帕氏疟原虫调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用,以响应氢气激活氢化酶表达。转录组分析表明,HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统,推定的甲酸盐转运蛋白和谷氨酰胺合成酶的基因的表达。 RPA0981在抑制氢化酶合成方面作用很小。我们还确定了两组分系统RegS-RegR抑制摄取氢化酶的表达,可能是响应细胞内氧化还原状态的变化。转录组分析表明,与缺乏摄取氢酶的突变菌株相比,当在固氮条件下在苹果酸上光异养生长时,利用氢的pal.ris细胞中约有30个基因差异表达。由此看来,还原剂以氢的形式的循环利用对R. palustris的基因表达没有广泛的非特异性影响。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录