• 【益生菌和益生元在慢性炎症性肠病中的作用。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i37.5941 复制DOI
    作者列表:Ewaschuk JB,Dieleman LA
    BACKGROUND & AIMS: :The prokaryotic and eukaryotic cells of the colon exist in a highly complex, but harmonious relationship. Disturbances in this remarkable symbiosis can result in the development of inflammatory bowel diseases (IBD). Although the etiology of IBD is not entirely understood, it is known that the chronic inflammation of Crohn's disease, ulcerative colitis and chronic pouchitis are a result of an overly aggressive immune response to the commensal intestinal flora in genetically susceptible hosts. Recent studies have enhanced our ability to understand the interaction between the host and its intestinal microflora and the role the microflora plays in maintaining intestinal homeostasis. As we begin to understand the benefits conferred to the intestine by the microflora, the notion of modifying the composition of the bacterial load to improve human health has arisen. A significant body of research now exists investigating the role of probiotics and prebiotics in ameliorating chronic intestinal inflammation. This article will begin with an overview of the role of the commensal microflora in maintaining mucosal immune homeostasis, and how a dysregulated immune response to the intestinal microflora results in IBD. This will be followed by a summary of the use of probiotics and prebiotics in experimental and human IBD.
    背景与目标: : 结肠的原核和真核细胞以高度复杂但和谐的关系存在。这种显着共生的干扰可能导致炎症性肠病 (IBD) 的发展。尽管IBD的病因尚不完全清楚,但众所周知,克罗恩病,溃疡性结肠炎和慢性胆囊炎的慢性炎症是对遗传易感宿主的共生肠道菌群过度激进的免疫反应的结果。最近的研究增强了我们了解宿主与其肠道菌群之间的相互作用以及微生物群在维持肠道稳态中的作用的能力。当我们开始了解微生物区系赋予肠道的益处时,就出现了改变细菌负荷的组成以改善人类健康的想法。目前存在大量研究,研究益生菌和益生元在改善慢性肠道炎症中的作用。本文将首先概述共生菌群在维持粘膜免疫稳态中的作用,以及对肠道菌群的免疫反应失调如何导致IBD。随后将总结益生菌和益生元在实验和人类IBD中的使用。
  • 【炎症性肠病的病因。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i30.4807 复制DOI
    作者列表:Danese S,Fiocchi C
    BACKGROUND & AIMS: :Theories explaining the etiopathogenesis of inflammatory bowel disease (IBD) have been proposed ever since Crohn's disease (CD) and ulcerative colitis (UC) were recognized as the two major forms of the disease. Although the exact cause(s) and mechanisms of tissue damage in CD and UC have yet to be completely understood, enough progress has occurred to accept the following hypothesis as valid: IBD is an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. Among an almost endless list of environmental factors, smoking has been identified as a risk factor for CD and a protective factor for UC. Among microbial factors, no convincing evidence indicates that classical infectious agents cause IBD, while mounting evidence points to an abnormal immune response against the normal enteric flora as being of central importance. Gut inflammation is mediated by cells of the innate as well as adaptive immune systems, with the additional contribution of non-immune cells, such as epithelial, mesenchymal and endothelial cells, and platelets.
    背景与目标: : 自从克罗恩病 (CD) 和溃疡性结肠炎 (UC) 被认为是炎症性肠病 (IBD) 的两种主要形式以来,就提出了解释炎症性肠病 (IBD) 病因的理论。尽管CD和UC组织损伤的确切原因和机制尚未完全了解,但已经取得了足够的进展,接受以下假设是有效的: IBD是一种不适当的免疫反应,由于遗传易感个体的结果环境因素之间的复杂相互作用,微生物因素和肠道免疫系统。在几乎无穷无尽的环境因素列表中,吸烟已被确定为CD的危险因素和UC的保护因素。在微生物因素中,没有令人信服的证据表明经典的感染因子引起IBD,而越来越多的证据表明针对正常肠道菌群的异常免疫反应至关重要。肠道炎症是由先天免疫系统和适应性免疫系统的细胞介导的,非免疫细胞 (例如上皮,间充质和内皮细胞以及血小板) 的额外贡献。
  • 【艾滋病患者的更昔洛韦耐药巨细胞病毒 (CMV) 视网膜炎病例: CMV病毒载量和血液区室病毒突变的纵向分子分析。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:1997-06-01
    来源期刊:AIDS
    DOI:10.1097/00002030-199707000-00005 复制DOI
    作者列表:Boivin G,Gilbert C,Morissette M,Handfield J,Goyette N,Bergeron MG
    BACKGROUND & AIMS: OBJECTIVE:To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis.

    METHODS:Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis.

    RESULTS:At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay.

    CONCLUSIONS:Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.

    背景与目标: 目标 : 研究巨细胞病毒 (CMV) 病毒载量与多形核白细胞 (PMNL) 和血浆样本中特定UL97突变之间的时间关系,该患者患有更昔洛韦耐药的CMV视网膜炎。
    方法 : 使用非分子方法和定量聚合酶链反应 (PCR) 分析方法分析了连续的PMNL和血浆样品,以确定CMV病毒载量。使用巢式PCR和限制性内切酶分析对相同样品进行了更昔洛韦抗性最常见突变的筛选。
    结果 : 在CMV视网膜炎进展时 (更昔洛韦6个月后),在PMNL和血浆样品中发现CMV DNA载量迅速增加。这种增加与同一样品中出现特定突变 (V594) 和更昔洛韦耐药血液分离株的回收平行。但是,在该患者中,唯一可以基本预测CMV疾病进展的测试是使用PMNL的定量PCR测定,以及在较小程度上使用pp65抗原血症测定。
    结论 : 使用敏感的检测方法 (例如PCR) 定量评估PMNL中的CMV病毒载量似乎是监测艾滋病患者抗病毒治疗的有希望的方法。此外,可以直接在PMNL和血浆样品中检测到赋予更昔洛韦抗性的常见突变。
  • 【罕见的疾病仍然是孤儿还是幸福地收养?开发和使用孤儿药品的挑战。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2125.2006.02654.x 复制DOI
    作者列表:Dear JW,Lilitkarntakul P,Webb DJ
    BACKGROUND & AIMS: :Orphan medicinal products (OMPs) are targeted at the diagnosis, prevention or treatment of rare diseases and have a special status in European law. This status brings incentives for pharmaceutical companies to invest in OMP development. The goal of the legislation is to encourage the development of more treatments for life-threatening rare disorders, but increased availability of OMPs raises important issues surrounding the public funding of very expensive treatments by national health services. In this article we review OMPs and the incentives for their development and discuss the challenges presented by funding these treatments.
    背景与目标: : 孤儿药品 (OMPs) 针对罕见疾病的诊断,预防或治疗,在欧洲法律中具有特殊地位。这种状态为制药公司投资OMP开发带来了动力。该立法的目标是鼓励为危及生命的罕见疾病开发更多的治疗方法,但是omp的可用性增加引发了围绕国家卫生服务机构为非常昂贵的治疗提供公共资金的重要问题。在本文中,我们回顾了omp及其发展的诱因,并讨论了资助这些治疗带来的挑战。
  • 【抗原特异性T细胞克隆在胶原疾病中的意义: 用新型T细胞克隆性评估系统分析。】 复制标题 收藏 收藏
    DOI:10.2169/internalmedicine.36.242 复制DOI
    作者列表:Yamamoto K
    BACKGROUND & AIMS: The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.

    背景与目标: 抗原特异性T细胞参与胶原疾病的发病机理仍存在争议。胶原蛋白疾病的最后阶段通常以炎症为主。因此,抗原非特异性因子 (如炎性细胞因子) 可能在这一过程中起重要作用。另一方面,用于分析免疫应答的抗原特异性方面的方法仍然有限。在这里,我们基于激活的抗原特异性T细胞应在淋巴细胞群体中形成累积克隆的想法,回顾了我们的新型T细胞克隆分析系统。使用该方法,可以在体内和体外评估抗原刺激过程中T细胞克隆积累的动态变化。使用类风湿关节炎和系统性红斑狼疮患者获得的数据讨论了抗原特异性T细胞克隆在胶原疾病中的意义。
  • 【HIV-1 RNA的运输由异质核核糖核蛋白A2表达介导,并影响病毒组装。】 复制标题 收藏 收藏
    DOI:10.1111/j.1600-0854.2006.00461.x 复制DOI
    作者列表:Lévesque K,Halvorsen M,Abrahamyan L,Chatel-Chaix L,Poupon V,Gordon H,DesGroseillers L,Gatignol A,Mouland AJ
    BACKGROUND & AIMS: :Few details are known about how the human immunodeficiency virus type 1 (HIV-1) genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is investigated in this study. Using immunofluorescence and fluorescence in situ hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1-expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a distinct, cytoplasmic space that corresponds to the microtubule-organizing center (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a result of hnRNP A2 knockdown even during the expression of a provirus harboring mutations in the hnRNP A2-response element (A2RE), the expression of which results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2 expression is required for downstream trafficking of genomic RNA from the MTOC in the cytoplasm. Genomic RNA localization at the MTOC that was both the result of hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein had little effect on pr55Gag synthesis but negatively influenced virus production and infectivity. These data indicate that altered HIV-1 genomic RNA localization modulates viral assembly and that the MTOC serves as a central site to which HIV-1 genomic RNA converges following its exit from the nucleus, with the host protein, hnRNP A2, playing a central role in taking it to and from this site in the cell.
    背景与目标: : 关于人类免疫缺陷病毒1型 (HIV-1) 基因组RNA如何在细胞质中运输的细节知之甚少。该过程的一部分受异质核核糖核蛋白A2 (hnRNP A2) 的活性控制。本研究研究了hnRNP A2在HeLa细胞中真正的前病毒表达中的作用。使用免疫荧光和荧光原位杂交技术,我们显示了HIV-1-expressing细胞中hnRNP A2表达的敲低导致HIV-1基因组RNA在与微管组织中心 (MTOC) 相对应的独特细胞质空间中快速积累。即使在hnRNP A2-response元件 (A2RE) 中携带突变的前病毒的表达过程中,由于hnRNP A2敲除,RNA也会在细胞核中离开并在MTOC区域积累,其表达导致基因组RNA的核保留。我们还证明hnRNP A2表达是细胞质中来自MTOC的基因组RNA下游运输所必需的。hnRNP A2敲低的结果和Rab7-interacting溶酶体蛋白的过表达在MTOC上的基因组RNA定位对pr55Gag的合成几乎没有影响,但对病毒的产生和感染性产生负面影响。这些数据表明,改变的HIV-1基因组RNA定位调节病毒组装,并且MTOC充当HIV-1基因组RNA从细胞核退出后会聚的中心位点,宿主蛋白hnrnpa2在将其带到和从细胞中的该位点中起着核心作用。
  • 7 Skin diseases in workers at a perfume factory. 复制标题 收藏 收藏

    【香水厂工人的皮肤病。】 复制标题 收藏 收藏
    DOI:10.1111/j.0105-1873.2006.00881.x 复制DOI
    作者列表:Schubert HJ
    BACKGROUND & AIMS: :The aim of this study is to find out the causes of skin diseases in one-third of the staff of a perfume factory, in which 10 different perfume sprays were being manufactured. Site inspection, dermatological examination and patch testing of all 26 persons at risk with 4 perfume oils and 30 ingredients of them. The results showed 6 bottlers were found suffering from allergic contact dermatitis, 2 from irritant contact dermatitis, 12 workers showed different strong reactions to various fragrances. The main causes of allergic contact dermatitis were 2 perfume oils (12 cases) and their ingredients geraniol (12 cases), benzaldehyde(9), cinnamic aldehyde (6), linalool, neroli oil, terpenes of lemon oil and orange oil (4 each). Nobody was tested positive to balsam of Peru. Job changes for office workers, packers or printers to other rooms, where they had no longer contact with fragrances, led to a settling. To conclude, automation and replacement of glass bottles by cartridges from non-fragile materials and using gloves may minimize the risk.
    背景与目标: : 这项研究的目的是找出3分之1一家香水工厂的工作人员的皮肤病的原因,该工厂生产了10种不同的香水喷雾剂。现场检查,皮肤科检查和所有26名有风险的人使用4种香料油和30种成分进行贴剂测试。结果显示,6名装瓶工人患有过敏性接触性皮炎,2名来自刺激性接触性皮炎,12名工人对各种香料表现出不同的强烈反应。过敏性接触性皮炎的主要病因为香精油2种 (12例),其成分为香叶醇 (12例),苯甲醛 (9例),肉桂醛 (6例),芳樟醇,橙花油,柠檬油和橙油的萜烯 (4例)。没有人对秘鲁的香脂测试呈阳性。办公室工作人员,包装工或打印机的工作变更到其他房间,他们不再与香水接触,导致了定居。总而言之,用非易碎材料和使用手套的墨盒自动化和更换玻璃瓶可以最大程度地降低风险。
  • 【结直肠腺癌和其他大肠疾病中的雌激素受体。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Sciascia C,Olivero G,Comandone A,Festa T,Fiori MG,Enrichens F
    BACKGROUND & AIMS: :Seventy-two patients with tumor and ten with non-neoplastic colon disease were studied for the presence of estrogen receptors (ER) by three different methods. Only seven specimens (six primary adenocarcinomas and one recurrent cancer) had an ER concentration above 3 fm/mg of cytosolic protein, with no sex, age and tumor stage correlation. Our results suggest that the large bowel does not contain a cytosolic receptor for estradiol.
    背景与目标: : 通过三种不同的方法研究了72例肿瘤患者和10例非肿瘤性结肠疾病的雌激素受体 (ER) 的存在。只有7个标本 (6个原发性腺癌和1个复发性癌症) 的ER浓度高于3 fm/mg的胞质蛋白,没有性别,年龄和肿瘤分期的相关性。我们的结果表明,大肠不含雌二醇的胞质受体。
  • 【居住在西西里岛东部卡塔尼亚的哥伦比亚和多米尼加女性性工作者中艾滋病毒和其他性传播疾病的流行。】 复制标题 收藏 收藏
    DOI:10.1007/s10903-006-9002-1 复制DOI
    作者列表:Nigro L,Larocca L,Celesia BM,Montineri A,Sjoberg J,Caltabiano E,Fatuzzo F,Unit Operators Group.
    BACKGROUND & AIMS: INTRODUCTION:STDs are a significant cause of illness throughout the world. Female sex workers (FSWs) are commonly perceived as belonging to a social group which may engage in high-risk behaviour for acquiring or transmitting HIV and other STDs. The number of immigrant women engaged in sex work has increased in Catania, Sicily, over the last 10 years. This study aims to estimate the prevalence of HIV, HBV, HCV and syphilis among Colombian and Dominican FSWs. METHODS:In total 118 (63.78%) of the FSWs contacted in the course of the project agreed to participate in the study. All women enrolled were counselled on STDs/HIV, safer sex practices and the use of condoms. Blood samples were taken and tested for HIV, HBV, HCV and syphilis. RESULTS:Of the 118 FSWs enrolled, all were negative for both HIV and HCV infection. Two women (1.6%) were positive for hepatitis B (HbsAg). Syphilis testing by VDRL showed three positive results (2.5%), which was confirmed by TPHA. DISCUSSION:This study showed that HIV, HBV, HCV and syphilis seroprevalence among Colombian and Dominican FSWs remains low or very rare. It also indicates that these women were healthy when they arrived in Italy and that condom use with clients is high.
    背景与目标:
  • 【病毒感染期间增强的IL-7信号传导驱动效应T细胞的更大扩增,但不增强记忆。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.177.7.4458 复制DOI
    作者列表:Sun JC,Lehar SM,Bevan MJ
    BACKGROUND & AIMS: :IL-7 signals are crucial for the survival of naive and memory T cells, and the IL-7R is expressed on the surface of these cells. Following viral infection, the IL-7R is expressed on only a subset of effector CD8 T cells, and has been demonstrated to be important for the survival of these memory precursors. IL-7 message levels remain relatively constant during the T cell response to lymphocytic choriomeningitis virus, but a short-lived burst of GM-CSF is observed soon after infection. Retroviral expression of a chimeric GM-CSF/IL-7R, in which binding of GM-CSF by T cells leads to IL-7 signaling, allows for the delivery of an IL-7 signal in all effector T cells expressing the receptor. In mice infected with lymphocytic choriomeningitis virus, CD8 and CD4 T cells transduced with this chimeric receptor underwent an enhanced proliferative response compared with untransduced populations in the same host. Similarly, TCR transgenic CD8 cells expressing the chimeric receptor produced higher effector numbers during the peak of the T cell response to infection. Surprisingly, the enhanced proliferation did not lead to higher memory numbers, as the subsequent contraction phase was more pronounced in the transduced cell populations. These findings demonstrate that artificial IL-7 signaling during an infection leads to significantly increased Ag-specific effector T cell numbers, but does not result in increased numbers of memory progeny. The extent of contraction may be dictated by intrinsic factors related to the number of prior cell divisions.
    背景与目标: : IL-7信号对于幼稚和记忆T细胞的存活至关重要,并且IL-7R在这些细胞的表面表达。病毒感染后,该IL-7R仅在效应cd8t细胞的子集上表达,并且已被证明对这些记忆前体的存活很重要。在T细胞对淋巴细胞性脉络丛脑膜炎病毒的反应期间,IL-7信息水平保持相对恒定,但是在感染后不久就观察到gm-csf的短暂爆发。嵌合gm-csf/IL-7R的逆转录病毒表达允许在表达该受体的所有效应T细胞中递送IL-7信号,其中gm-csf被T细胞结合导致IL-7信号。在感染了淋巴细胞性脉络丛脑膜炎病毒的小鼠中,与同一宿主中未转导的人群相比,用该嵌合受体转导的CD8和CD4 T细胞的增殖反应增强。同样,表达嵌合受体的TCR转基因CD8细胞在T细胞对感染的反应高峰期间产生更高的效应子数。令人惊讶的是,增强的增殖并未导致更高的记忆数,因为随后的收缩阶段在转导的细胞群体中更为明显。这些发现表明,感染期间的人工IL-7信号传导导致Ag特异性效应T细胞数量显着增加,但不会导致记忆后代数量增加。收缩的程度可能取决于与先前细胞分裂数量相关的内在因素。
  • 【接受社区精神病护理的严重精神疾病患者的口腔疾病患病率和与口腔健康相关的生活质量。】 复制标题 收藏 收藏
    DOI:10.1038/sj.bdj.2012.989 复制DOI
    作者列表:Patel R,Gamboa A
    BACKGROUND & AIMS: OBJECTIVES:To describe the prevalence of oral diseases and their impact on oral-health-related quality of life in people with severe mental illness undertaking community-based psychiatric care. METHODS:A survey was conducted at eight outpatient psychiatric care clinics in Tower Hamlets, London, UK. One hundred and twelve consecutive patients with mental illness were invited to participate in this study. They were clinically examined and asked to complete the oral health impact profile (OHIP) questionnaire. RESULTS:The response rate was 79% (n = 89); 57 (64%) males and 58 persons over 45 years of age (65%) participated in this survey. Overall OHIP score was 25.4 (95% CI 23.3, 27.4), 70 (78%) were smokers and 45 (51%) had been to the dentist in the last two years. Forty-seven (53%) respondents had caries in at least one tooth, 60 (67%) had 21 teeth and more, and 14 (16%) used dentures. Advanced periodontal treatment was indicated in 42 (55%) of patients and 52.8% (n = 47) patients reported current pain. CONCLUSION:Overall, this survey found that oral health has a great impact on patients with severe mental illness being treated in the community setting and their oral health is poorer than the national adult general population. Future research should consider the causes that relate to the poorer oral health in this population and potential health promotion mechanisms in this population to encourage an upstream approach to health.
    背景与目标:
  • 【甲状腺疾病的细针穿刺细胞学检查。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Altavilla G,Pascale M,Nenci I
    BACKGROUND & AIMS: :From 1982 to 1987, 2,433 lesions of the thyroid gland in 1,796 patients were examined by fine needle aspiration (FNA). Cytopathology classified 66.91% of the aspirates as benign, 10.76% as thyroiditis, 4.89% as suspected (unspecified) neoplasia, 1.31% as positive for malignancy and 16.11% (392) as unsatisfactory. The histologic diagnoses in 257 cases were compared with cytologic diagnoses to determine the accuracy of FNA cytology of thyroid lesions, yielding a sensitivity of 71.43%, a specificity of 100% and an accuracy of 95.09%. This data strongly supports thyroid FNA as an important preoperative diagnostic tool. Follicular carcinomas were difficult to cytologically differentiate from nonmalignant follicular neoplasms, and papillary thyroid carcinomas less than 2 cm in diameter in elderly patients were frequently misdiagnosed or diagnosed only as "suspect lesion."
    背景与目标: : 从1982个1987年中,通过细针穿刺 (FNA) 检查了1,796例患者的2,433个甲状腺病变。细胞病理学将66.91% 抽吸物分类为良性,10.76% 为甲状腺炎,4.89% 为疑似 (未指定) 肿瘤,1.31% 为恶性肿瘤阳性,16.11% (392) 为不满意。将257例的组织学诊断与细胞学诊断进行比较,以确定甲状腺病变的FNA细胞学检查的准确性,从而产生71.43% 的敏感性,100% 的特异性和95.09% 的准确性。该数据强烈支持甲状腺FNA作为重要的术前诊断工具。滤泡癌在细胞学上很难与非恶性滤泡肿瘤区分开来,而老年患者直径小于2厘米的甲状腺乳头状癌经常被误诊或仅被诊断为 “可疑病变”。
  • 【在ALS4-like运动神经元疾病患者中评估的SETX错义变异谱。】 复制标题 收藏 收藏
    DOI:10.1007/s10048-012-0347-4 复制DOI
    作者列表:Arning L,Epplen JT,Rahikkala E,Hendrich C,Ludolph AC,Sperfeld AD
    BACKGROUND & AIMS: :Mutations in the senataxin (SETX) gene can cause amyotrophic lateral sclerosis 4 (ALS4), an autosomal dominant form of juvenile onset amyotrophic lateral sclerosis, or result in autosomal recessive ataxia with oculomotor apraxia type 2. Great caution regarding the possible disease causation, especially of missense variations, has to be taken. Here, we evaluated the significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having ALS4. Yet, epidemiologic and in silico evidence indicates that all newly identified variations and two previously published ALS4-related missense variations (C1554G and I2547T) are most likely non-pathogenic, demonstrating the problems of interpretation of SETX missense alleles in the absence of functional assays.
    背景与目标: : senataxin (SETX) 基因的突变可导致肌萎缩性侧索硬化症4 (ALS4),这是一种常染色体显性遗传形式的少年性肌萎缩性侧索硬化症,或导致常染色体隐性遗传性共济失调并伴有动眼失用2型。对于可能的疾病原因,尤其是错义变异,必须谨慎行事。在这里,我们评估了所有先前报道的SETX错义突变以及54例怀疑患有als4的患者中新发现的六个变异的重要性。然而,流行病学和计算机证据表明,所有新发现的变异和两个先前发表的ALS4-related错义变异 (C1554G和I2547T) 最有可能是非致病性的,证明了在缺乏功能测定的情况下解释SETX错义等位基因的问题。
  • 【N-{4-[5-(4-氟苯基)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-乙酰胺 (CBS-3595),一种对tnf α 相关疾病具有活性的p38α MAPK/PDE-4双重抑制剂.】 复制标题 收藏 收藏
    DOI:10.1021/acs.jmedchem.6b01647 复制DOI
    作者列表:Albrecht W,Unger A,Bauer SM,Laufer SA
    BACKGROUND & AIMS: :The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38α MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.
    背景与目标: : p38丝裂原活化蛋白激酶 (MAPK) 抑制剂的抗炎潜力被巧合地扩展为对p38α MAPK和磷酸二酯酶4 (PDE4) 的双重抑制,并且两种炎症相关酶的阻断所产生的潜在益处被彻底研究。在对啮齿动物,狗和猴子施用1之后,在体外实验以及体外和体内临床前研究中相继评估了最有希望的化合物CBS-3595 (1)。所得数据清楚地表明有效抑制了肿瘤坏死因子 α 的释放。为了在向健康的人类志愿者施用1时再次确认动物研究的结果,进行了I期临床试验。除了有关1的药代动力学和药效学特征的进一步信息外,还证明了p38α MAPK和PDE4的双重抑制能够协同减弱过度的抗炎反应。
  • 【使用手持式便携式非散瞳眼底照相机对视网膜疾病进行远程医疗筛查。】 复制标题 收藏 收藏
    DOI:10.1186/s12886-017-0484-5 复制DOI
    作者列表:Jin K,Lu H,Su Z,Cheng C,Ye J,Qian D
    BACKGROUND & AIMS: BACKGROUND:We modified and reconstructed a high image quality portable non-mydriatic fundus camera and compared it with the tabletop fundus camera to evaluate the efficacy of the new camera in detecting retinal diseases. METHODS:We designed and built a novel portable handheld fundus camera with telemedicine system. The image quality of fundus cameras was compared to that of existing commercial tabletop cameras by taking photographs of 364 eyes from the 254 patients. In all 800 fundus images taken by two camera types, 400 images per camera, were graded with the four image clarity classifications. RESULTS:Using the portable fundus camera, 63% (252/400) images were graded as excellent overall quality, 20.5% (82/400) were good, 11.75% (47/400) were fair, and 4.75% (19/400) were inadequate. Using the tabletop fundus camera, 70.75% (283/400) images were graded as excellent overall quality, 20.4% (51/400) were good, 13.25% (53/400) were fair, and 3.25% (13/400) were inadequate. Common retinal diseases were easily identified from fundus images obtained from the portable fundus camera. CONCLUSION:The new type of non-mydriatic portable fundus camera was qualified to have professional quality of fundus images. The revolutionary screening camera provides a foundational platform which can potentially improve the accessibility of retinal screening programmes.
    背景与目标:

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