• 【神经放射学专业专家对脑CT成像研究进行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: 目的:确定亚专业专家对临床管理变化进行重新解释的脑部CT成像研究的临床重要性和相对价值。
    方法:在2002年至2003年期间,在两家机构中查询了计算机记录,以获取由董事会认证的非神经放射科医生进行的主要解释,以及由三位神经放射科医生进行的次要解释。总共审查了1,081例。最初,每个案例都被解释为紧急研究。重新解释的研究被专业专家评定为一致或不一致。如果临床管理发生变化,则将不一致的研究分类为“重大不一致”,如果临床管理没有影响或发生变化,则将其分类为“较小不一致”。
    结果:在所审查的1,081项研究中,有14项研究被确定为不一致(1.3%)。在这些不一致的研究中,有四项被归类为需要改变临床管理的主要差异(0.4%)。十个分类为轻微差异(0.9%)。任何差异都不会在发病率和死亡率方面带来永久性的不良后果。
    结论:经董事会认证的一般放射科医生阅读的绝大多数解释性头部CT病例,经专科专家验证,并不会导致不一致的解释。在大多数情况下,不一致的解释并不会导致临床管理的改变。专科专家对头颅CT进行双重读取似乎是一种实质上改善影像健康质量结果的无效方法。
  • 【自我收集的宫颈阴道取样,用于基于医疗地点的基于HPV的子宫颈癌初步筛查:在农村服务水平不高的希腊人口中进行的一项初步研究。】 复制标题 收藏 收藏
    DOI:10.1080/01443615.2017.1323197 复制DOI
    作者列表:Chatzistamatiou K,Chatzaki Ε,Constantinidis Τ,Nena E,Tsertanidou A,Agorastos T
    BACKGROUND & AIMS: :In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.
    背景与目标: :在本项初步研究中,对希腊北部农村地区服务水平低下的346名妇女进行了基于宫颈癌阴道自我采样方法的HPV筛查的可行性的测试。这些妇女提供了自己收集的宫颈阴道样本以及研究问卷。在进行分子测试后,使用cobas®HPV测试,将Roche®,HPV阳性女性进行阴道镜检查,并在发现异常后进行活检和治疗。参与率为100%。定期进行巴氏试验检查的报道为17.1%。在hrHPV测试中,有11.9%呈阳性,阴道镜检查/活检显示有2例CIN3病例。不遵守是没有参加会议的最普遍原因。大多数妇女在自我抽样中报告没有困难和不舒服(分别为77.6%和82.4%)。他们将选择自采样而不是临床医生采样(86.2%),并且如果可以使用自采样,他们将更定期地进行自我测试(92.3%)。总之,对于基于HPV的筛查,自我抽样是可行的并且被广泛接受,并且可以扩大服务不足地区的人口覆盖率,有助于成功进行预防。
  • 【在新发作的急诊科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: :急诊科通常会对新发作的癫痫患者进行广泛的实验室检查。为了确定此类测试的实用性,对在市内大学附属教学医院急诊室就诊的新发癫痫患者进行了一项前瞻性研究。在1984年10月至1988年1月之间,共有136例患者进入研究。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共同原因之前,以标准化的形式记录相关的历史信息和体格检查结果。这些患者包括四名低血糖患者,四名高血糖患者,两名低钙血症患者和一名低镁血症患者。根据病史或体格检查的结果,仅怀疑2例(低血糖)。在ED患者中,由于可纠正的代谢紊乱引起的新发作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,不必要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的测试顺序应由病史和体格检查指示。
  • 【假定眼结核患者通过正电子发射断层扫描/计算机断层扫描(PET / CT)研究系统摄取18-FDG的模式。】 复制标题 收藏 收藏
    DOI:10.3109/09273948.2012.697596 复制DOI
    作者列表:Mehta S
    BACKGROUND & AIMS: AIM:To report the patterns and sites of 18-FDG uptake in patients of presumed ocular tuberculosis. MATERIALS AND METHODS:The clinical and investigational findings of 11 patients were reviewed retrospectively. These included 6 males and 5 females with a mean age of 46.2 years. 21 eyes were included in the data analysis. Clinical presentations include 15 eyes with anterior uveitis, 2 eyes with retinal vasculitis, 2 eyes with panuveitis and 2 eyes with multifocal choroidopathy. RESULTS:Two distinct patterns of systemic uptake emerged. Pattern 1: No detectable systemic uptake (4 patients). Pattern 2: Detectable systemic uptake. a. Chest disease only (2 patients). b. Disseminated pattern, uptake seen at multiple sites (4 patients). c. Extrapulmonary only (1 patient). CONCLUSIONS:Ocular tuberculosis may often be part of a wider disseminated disease.
    背景与目标: 目的:报告推测的眼结核患者摄取18-FDG的方式和部位。
    材料与方法:回顾性分析11例患者的临床和研究结果。其中包括6名男性和5名女性,平均年龄为46.2岁。数据分析包括21只眼睛。临床表现包括前葡萄膜炎15眼,视网膜血管炎2眼,胰腺炎2眼和多灶性脉络膜病变2眼。
    结果:出现了两种不同的全身吸收模式。模式1:未检测到全身吸收(4例患者)。模式2:可检测到的全身吸收。一种。仅胸部疾病(2例)。 b。分布模式,在多个部位可见吸收(4例)。 C。仅肺外(1例患者)。
    结论:眼结核通常可能是更广泛传播的疾病的一部分。
  • 【在自身免疫性甲状腺疾病中甲状腺球蛋白特异性抑制性T细胞功能的研究。】 复制标题 收藏 收藏
    DOI:10.1210/jcem-61-2-306 复制DOI
    作者列表:Mori H,Hamada N,DeGroot LJ
    BACKGROUND & AIMS: :T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.
    背景与目标: :使用自身免疫性甲状腺疾病患者的淋巴细胞研究了甲状腺球蛋白斑块形成细胞(Tg PFC)和蛋白A斑块形成细胞(Prot A PFC)生成的T细胞调节。在无有丝分裂或抗原刺激的情况下进行T细胞和B细胞混合培养(T-B MC),以鉴定系统中的生理性T细胞效应。在血清中滴度高的甲状腺球蛋白抗体的18例患者中,有8例(44%)发现了Tg PFC。使用来自这八名患者的B细胞在T-B MC系统中研究了来自患者和正常受试者的T细胞的Tg特异性和非特异性免疫调节。在添加T细胞后,发现Tg PFC诱导的值比Prot A PFC诱导的低得多。正常T细胞抑制Tg PFC诱导,但对患者T细胞没有抑制作用,而通过添加患者和正常T细胞对Prot A PFC诱导发现了相同程度的辅助作用。患者和正常受试者的T细胞辐射(1500 rads)显着增强了TgPFC和Prot A PFC的诱导作用。因此,Tg特异性抑制T细胞作为放射抑制性T细胞亚群的一部分存在于所有正常受试者中。由辐射诱导的Tg特异性抑制T细胞功能的抑制引起的Tg-PFC的增加在正常受试者中比在患者中显着更大。在自体T-B MC系统中,带有组胺2型受体的T细胞抑制Prot A PFC诱导,但不抑制Tg PFC诱导。正常B细胞​​与未经治疗的T细胞,经辐照的T细胞或来自患者或正常受试者的组胺2型受体阴性T细胞的任何组合均未诱导Tg PFC。这些数据表明,可以通过使用来自自身免疫性甲状腺疾病患者血清中Tg抗体滴度高的患者的B细胞,在T-B MC系统中研究体外Tg特异性T细胞调节。 Tg特异性抑制性T细胞似乎存在于所有个体中,并参与Tg抗体产生的调节。与正常受试者相比,患者中Tg特异性抑制性T细胞的活性较低可能与体内Tg抗体的产生有关。然而,这种异常是异质的,不是完全的,而是Tg特异性抑制性T细胞的相对缺陷。
  • 【模拟复杂数据结构以计划研究,重点是生物标记物比较。】 复制标题 收藏 收藏
    DOI:10.1186/s12874-017-0364-y 复制DOI
    作者列表:Schulz A,Zöller D,Nickels S,Beutel ME,Blettner M,Wild PS,Binder H
    BACKGROUND & AIMS: BACKGROUND:There are a growing number of observational studies that do not only focus on single biomarkers for predicting an outcome event, but address questions in a multivariable setting. For example, when quantifying the added value of new biomarkers in addition to established risk factors, the aim might be to rank several new markers with respect to their prediction performance. This makes it important to consider the marker correlation structure for planning such a study. Because of the complexity, a simulation approach may be required to adequately assess sample size or other aspects, such as the choice of a performance measure. METHODS:In a simulation study based on real data, we investigated how to generate covariates with realistic distributions and what generating model should be used for the outcome, aiming to determine the least amount of information and complexity needed to obtain realistic results. As a basis for the simulation a large epidemiological cohort study, the Gutenberg Health Study was used. The added value of markers was quantified and ranked in subsampling data sets of this population data, and simulation approaches were judged by the quality of the ranking. One of the evaluated approaches, the random forest, requires original data at the individual level. Therefore, also the effect of the size of a pilot study for random forest based simulation was investigated. RESULTS:We found that simple logistic regression models failed to adequately generate realistic data, even with extensions such as interaction terms or non-linear effects. The random forest approach was seen to be more appropriate for simulation of complex data structures. Pilot studies starting at about 250 observations were seen to provide a reasonable level of information for this approach. CONCLUSIONS:We advise to avoid oversimplified regression models for simulation, in particular when focusing on multivariable research questions. More generally, a simulation should be based on real data for adequately reflecting complex observational data structures, such as found in epidemiological cohort studies.
    背景与目标: 背景技术:越来越多的观察性研究不仅专注于单个生物标志物来预测结果事件,而且在多变量环境中解决问题。例如,当量化除已建立的风险因素外的新生物标记物的附加值时,目标可能是就其预测性能对几种新标记物进行排名。因此,重要的是要考虑标记物相关结构以进行此类研究。由于其复杂性,可能需要一种仿真方法来充分评估样本大小或其他方面,例如性能指标的选择。
    方法:在基于真实数据的模拟研究中,我们调查了如何生成具有实际分布的协变量,以及应使用哪种生成模型进行结果计算,旨在确定获得实际结果所需的最少信息量和复杂度。大型流行病学队列研究作为模拟的基础,使用了古腾堡健康研究。对标记的增加值进行量化,并在该总体数据的子采样数据集中进行排名,并根据排名的质量来判断模拟方法。评估方法之一是随机森林,它需要各个级别的原始数据。因此,还研究了基于随机森林的模拟试验研究规模的影响。
    结果:我们发现简单的逻辑回归模型无法充分生成现实数据,即使具有交互项或非线性效应等扩展。人们认为,随机森林方法更适合于复杂数据结构的仿真。从大约250个观察值开始的试点研究被认为为该方法提供了合理水平的信息。
    结论:我们建议避免过度简化的回归模型进行仿真,尤其是在关注多变量研究问题时。更一般而言,模拟应基于真实数据,以充分反映复杂的观察数据结构,例如流行病学队列研究中发现的结构。
  • 【维生素D缺乏症对亚临床颈动脉粥样硬化的影响:队列研究的汇总分析。】 复制标题 收藏 收藏
    DOI:10.1210/jc.2017-00342 复制DOI
    作者列表:Lupoli R,Vaccaro A,Ambrosino P,Poggio P,Amato M,Di Minno MN
    BACKGROUND & AIMS: Context:Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective:To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources:Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results:Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions:Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.
    背景与目标: 背景:维生素D缺乏症患者的心血管(CV)发病率和死亡率增加。颈动脉内膜中层厚度(IMT)和颈动脉斑块是亚临床动脉粥样硬化的标志物和CV事件的预测因子。
    目的:进行荟萃分析,评估维生素D缺乏对颈总动脉IMT(CCA-IMT)和颈动脉斑块患病率的影响。
    数据来源:在PubMed,Web of Science,Scopus和EMBASE数据库中系统地搜索了研究。
    结果:包括21项研究(3,777例维生素D缺乏症患者和4,792例对照者)的CCA-IMT数据和6项研究(1,889例D维生素D缺乏症患者和2,883例对照者)的颈动脉斑块患病率。与对照组相比,维生素D缺乏症患者的CCA-IMT显着更高(平均差异[MD]:0.043毫米; 95%CI:0.030,0.056; P <0.001),并且颈动脉斑块的患病率增加(几率[OR] ]:2.29,95%CI:1.03-5.11; P = 0.043),归因风险为35.9%。在选择专门针对糖尿病患者的研究时,维生素D缺乏症患者的颈动脉斑块患病率高于对照组(OR:3.27; 95%CI:1,62-6.62; P = 0.001)。当将维生素D功能不足的患者与对照组进行比较时,证实了CCA-IMT的显着差异(MD:0.011; 95%CI:0.010-0.012,P <0.001)。敏感性分析基本证实了结果,回归模型显示,除了低密度脂蛋白胆固醇,高密度脂蛋白胆固醇,甘油三酸酯和高胆固醇血症的患病率外,所有其他临床和人口统计学共同变量均显着影响维生素D之间CCA-IMT的差异缺乏患者和对照。
    结论:维生素D缺乏症和维生素D缺乏症均与亚临床动脉粥样硬化有关,可能提示在这些临床情况下CV风险增加。
  • 【对三叶薄荷的抗炎研究与显示对大鼠肾衰竭的作用有关。】 复制标题 收藏 收藏
    DOI:10.1016/S0944-7113(11)80054-1 复制DOI
    作者列表:Tunón H,Bohlin L
    BACKGROUND & AIMS: :Menyanthes trifoliata L. is used in Swedish traditional medicine for the treatment of inflammatory diseases of the kidney, e.g. glomerulonephritis. Earlier studies have shown that MtL increases glomerular filtration rate after renal reperfusion ischemia. This activity was suggested to be PAF-inhibitory since MtL also inhibited PAF-induced exocytosis in vitro on human neutrophils (IC(50) = 0.16 mg/ml). The present study further characterizes the anti-inflammatory properties of a rhizome decoction of this plant. MtL inhibited carrageenan-induced rat paw edema (ID(50) ≈ 1.7 g/kg p.o.) and ethyl phenylpropiolate-induced rat ear edema (32% at 2.0 g/kg p.o.) in a dose-dependent manner. Further studies revealed that MtL inhibited both fMLP-induced exocytosis (IC(50) = 0.16 mg/ml) and elastase activity (IC(50) = 0.16 mg/ml). According to these results it is likely that the activity shown in the PAF-test is at least partly due to an inhibition of elastase. MtL showed only minor hemolytic properties at the concentrations used in the PAF- and fMLP-tests, suggesting that the cells in these tests are undamaged. The decoction also inhibited the biosynthesis of LTB(4) (IC(50) ≈ 0.73 mg/ml) and prostaglandins (IC(50) = 0.37 mg/ml) in vitro in a concentration-dependent way. However, at concentrations where the decoction is active in the LTB(4)-test, it also possesses hemolytic properties.
    背景与目标: :Menyanthes trifoliata L.在瑞典传统医学中用于治疗肾脏的炎症性疾病,例如肾小球肾炎。较早的研究表明,肾脏缺血再灌注后MtL可提高肾小球滤过率。该活性被认为是抑制PAF的,因为MtL还可以在体外抑制人嗜中性粒细胞的PAF诱导的胞吐作用(IC(50)= 0.16 mg / ml)。本研究进一步表征了该植物的根茎煎剂的抗炎特性。 MtL以剂量依赖性方式抑制角叉菜胶诱导的大鼠爪水肿(ID(50)≈1.7 g / kg p.o.)和苯丙酸乙酯诱导的大鼠耳水肿(2.0 g / kg p.o.时32%)。进一步的研究表明,MtL抑制fMLP诱导的胞吐作用(IC(50)= 0.16 mg / ml)和弹性蛋白酶活性(IC(50)= 0.16 mg / ml)。根据这些结果,PAF-测试中显示的活性可能至少部分是由于弹性蛋白酶的抑制。在PAF和fMLP测试中使用的浓度下,MtL仅显示出较小的溶血特性,表明这些测试中的细胞未受损。该汤还以浓度依赖的方式抑制了LTB(4)(IC(50)≈0.73 mg / ml)和前列腺素(IC(50)= 0.37 mg / ml)的生物合成。但是,在LTB(4)测试中该汤具有活性的浓度下,它也具有溶血作用。
  • 【角膜和皮肤的伤口愈合研究:平行,差异和机会。】 复制标题 收藏 收藏
    DOI:10.3390/ijms18061257 复制DOI
    作者列表:Bukowiecki A,Hos D,Cursiefen C,Eming SA
    BACKGROUND & AIMS: :The cornea and the skin are both organs that provide the outer barrier of the body. Both tissues have developed intrinsic mechanisms that protect the organism from a wide range of external threats, but at the same time also enable rapid restoration of tissue integrity and organ-specific function. The easy accessibility makes the skin an attractive model system to study tissue damage and repair. Findings from skin research have contributed to unravelling novel fundamental principles in regenerative biology and the repair of other epithelial-mesenchymal tissues, such as the cornea. Following barrier disruption, the influx of inflammatory cells, myofibroblast differentiation, extracellular matrix synthesis and scar formation present parallel repair mechanisms in cornea and skin wound healing. Yet, capillary sprouting, while pivotal in proper skin wound healing, is a process that is rather associated with pathological repair of the cornea. Understanding the parallels and differences of the cellular and molecular networks that coordinate the wound healing response in skin and cornea are likely of mutual importance for both organs with regard to the development of regenerative therapies and understanding of the disease pathologies that affect epithelial-mesenchymal interactions. Here, we review the principal events in corneal wound healing and the mechanisms to restore corneal transparency and barrier function. We also refer to skin repair mechanisms and their potential implications for regenerative processes in the cornea.
    背景与目标: :角膜和皮肤都是提供身体外部屏障的器官。两种组织都已开发出内在机制,可以保护生物体免受各种外部威胁的侵害,但同时也可以快速恢复组织的完整性和器官特异性功能。易于访问使皮肤成为研究组织损伤和修复的有吸引力的模型系统。皮肤研究的发现有助于揭示再生生物学的新基本原理,并修复了其他上皮-间质组织,例如角膜。屏障破坏后,炎症细胞的涌入,成肌纤维细胞的分化,细胞外基质的合成和疤痕的形成在角膜和皮肤伤口愈合中呈现出平行的修复机制。然而,毛细血管发芽虽然在适当的皮肤伤口愈合中起关键作用,但它是与角膜的病理修复相关的过程。对于再生疗法的发展以及对影响上皮-间质相互作用的疾病病理学的理解,了解协调皮肤和角膜伤口愈合反应的细胞和分子网络的相似性和差异性可能对两个器官都具有共同的重要性。在这里,我们回顾了角膜伤口愈合中的主要事件以及恢复角膜透明性和屏障功能的机制。我们还提到皮肤修复机制及其对角膜再生过程的潜在影响。
  • 【肌肉收缩中跨桥作用的X射线研究:快速释放的证据。】 复制标题 收藏 收藏
    DOI:10.1016/j.jmb.2006.08.075 复制DOI
    作者列表:Huxley H,Reconditi M,Stewart A,Irving T
    BACKGROUND & AIMS: :We have used a high-resolution small angle X-ray scattering system, together with a high-performance CCD camera, on the BioCAT beamline at the APS synchrotron radiation facility at the Argonne National Laboratory, to study X-ray interference effects in the meridional reflections generated by the arrays of myosin crossbridges in contracting muscle. These give information about axial movements of the myosin heads during contraction with sub-nanometer resolution. Using whole intact muscle preparations (frog sartorius) we have been able to record the detailed behavior of M3 (the first order meridional reflection from the myosin crossbridges, at 14.56 nm) at each of a number of quick releases of increasing magnitude, on the same specimen, and at the same time make similar measurements on higher order myosin meridional reflections, particularly M6. The latter provides information about the dispersion of lever arm angles of the actin-attached myosin heads. The observations show that in isometric contraction the lever arm angles are dispersed through +/- 20-25 degrees on either side of a mean orientation that is about 60 degrees away from their orientation at the end of the working stroke: and that they move towards that orientation in synchronized fashion, with constant dispersion, during quick releases. The relationship between the shift in the interference fringes (which measures the shift of the myosin heads scattering mass towards the center of the sarcomere, and the changes in the total intensity of the reflections, which measures the changes in the axial profile of the heads, is consistent with the tilting lever arm mechanism of muscle contraction. Significant fixed contributions to the meridional reflections come from unattached myosin heads and from backbone components of the myosin filaments, and the interaction of these with the contributions from actin-attached myosin heads determines the behavior of these reflections.
    背景与目标: :我们在Argonne国家实验室的APS同步加速器辐射设施的BioCAT光束线上使用了高分辨率小角度X射线散射系统以及高性能CCD相机,研究了X射线干扰效应。收缩肌中肌球蛋白横桥阵列产生的子午反射。这些以亚纳米分辨率给出有关收缩期间肌球蛋白头的轴向运动的信息。使用完整的完整肌肉制备物(青蛙sartorius),我们能够在相同的数量的多个快速释放中,分别记录M3的详细行为(来自肌球蛋白交叉桥的一阶子午反射,在14.56 nm处)。标本,同时对高阶肌球蛋白子午线反射(特别是M6)进行类似的测量。后者提供了有关附有肌动蛋白的肌球蛋白头的杠杆臂角度分散的信息。观察结果表明,在等距收缩中,杠杆臂角度在平均方向的任一侧上通过20-25度分散,该平均方向与工作行程结束时的方向相差约60度:并且它们朝着该方向移动在快速释放过程中,以同步的方式进行定向,并具有恒定的分散性。干涉条纹的偏移(用于测量肌球蛋白头部散射质量向肌小节中心的偏移)与反射总强度的变化(用于测量头部的轴向轮廓的变化)之间的关系,与倾斜杠杆臂的肌肉收缩机制相一致,对子午反射的重要固定贡献来自未附着的肌球蛋白头部和肌球蛋白丝的骨架成分,这些相互作用与肌动蛋白附着的肌球蛋白头部的相互作用决定了行为这些思考。
  • 【体内成像研究揭示了生发中心的发育。】 复制标题 收藏 收藏
    DOI:10.1038/nri2120 复制DOI
    作者列表:Hauser AE,Shlomchik MJ,Haberman AM
    BACKGROUND & AIMS: :Affinity maturation of antibodies during the course of an adaptive immune response requires germinal centre (GC) formation within B-cell follicles. Much of the current understanding of GC function has been derived from histology, but these static views have left unresolved many questions about cell movement in GCs. In this Progress article, we describe how several recent studies using time-resolved multiphoton microscopy to track GC B-cell movement within lymph nodes have shed light on the processes that influence GC B-cell dynamics.
    背景与目标: 在适应性免疫反应过程中,抗体的亲和力成熟需要B细胞卵泡内生发中心(GC)的形成。当前对GC功能的大多数了解都来自组织学,但是这些静态视图尚未解决许多有关GC中细胞运动的问题。在这篇“进步”文章中,我们描述了最近几项使用时间分辨多光子显微镜跟踪淋巴结内GC B细胞运动的研究如何阐明了影响GC B细胞动力学的过程。
  • 【颞中叶癫痫的成年神经发生:近期动物和人类研究的回顾。】 复制标题 收藏 收藏
    DOI:10.2174/138920107780906504 复制DOI
    作者列表:Liu YW,Mee EW,Bergin P,Teoh HH,Connor B,Dragunow M,Faull RL
    BACKGROUND & AIMS: :Mesial temporal lobe epilepsy (mTLE) is a neurological condition characterized by the occurrence of spontaneous recurrent seizures originating from mesial structures involving the hippocampus within the temporal lobe. This condition is often associated with pathological features in the hippocampus such as neuronal cell loss, widening of the granule cell layer, astrogliosis and mossy fibre spouting. At present, the mechanisms underlying these pathological features are unclear. However, recent advances in adult neurogenesis studies in mTLE animals and patients suggest that newly generated neurons may contribute to the pathogenesis of ongoing epileptogenesis. This article will review the recent animal and human studies on adult neurogenesis in mTLE and discuss how these results suggests that adult endogenous neurogenesis may not always be reparative in the mTLE and may be targeted in new therapeutic strategies for mTLE.
    背景与目标: :颞中叶癫痫(mTLE)是一种神经系统疾病,其特征是发生自发性复发性癫痫发作,这种发作是由颞叶内涉及海马体的中枢结构引起的。这种情况通常与海马的病理特征有关,例如神经元细胞丢失,颗粒细胞层变宽,星形胶质细胞增多和苔藓纤维喷出。目前,尚不清楚这些病理特征的潜在机制。但是,mTLE动物和患者的成人神经发生研究的最新进展表明,新产生的神经元可能与正在进行的癫痫发生的发病机理有关。本文将回顾有关mTLE中成人神经发生的最新动物和人类研究,并讨论这些结果如何表明成人内源性神经发生在mTLE中可能并不总是可修复的,并且可能成为mTLE新治疗策略的目标。
  • 【生长激素结合蛋白:II。在侏儒症和正常受试者中进行的研究。】 复制标题 收藏 收藏
    DOI:10.1210/jcem-71-5-1183 复制DOI
    作者列表:Merimee TJ,Baumann G,Daughaday W
    BACKGROUND & AIMS: :The serum concentrations of a specific GH-binding protein, derived from the GH receptor, were assayed in sera from 62 African pygmies and 101 normal statured controls. Samples were assayed in the absence and presence of excess GH using 2 separatory procedures. Interassay variability for samples was corrected by a standard reference pool of sera from adults assayed with all unknown samples. Results were expressed as specific binding relative to this standard. The mean percent relative specific binding for GH increased with age in normal-statured controls throughout childhood and adolescence. Relative specific binding for GH was 37.0 +/- 2.0% (mean +/- SEM) in control subjects between the ages of 1-5 yr (mean age, 2.9 yr) and increased progressively to 93.0 +/- 7.0% in young adults (mean age, 23 yr). The relative specific binding of GH by serum from pygmies did not exceed 30.1 +/- 3.4% of the control adult standard at any age period (P less than 0.001), and there was no progressive age-related increase in binding. The decrease from normal binding was minimal in pygmies during childhood (29%), but the decrease from normal was 60-70% in adolescents and adults. Thus, short stature in pygmies probably results not from an absolute deficiency of GH receptors per se, as in Laron dwarfism, but from a failure of cellular GH receptors to increase in a normal manner. This is most compatible with a change in regulating expression of the GH receptor gene, rather than a structural defect in the coding sequence of the GH receptor gene.
    背景与目标: :在来自62个非洲鼠和101个正常对照的血清中测定了从GH受体衍生的特定GH结合蛋白的血清浓度。使用2种分离方法在不存在和存在过量GH的情况下分析样品。通过使用所有未知样品进行分析的成人血清标准参比库对样品的测定间变异性进行了校正。结果表示为相对于该标准的特异性结合。在整个童年和青春期,正常控制的对照组中GH的平均相对特异性结合百分比随年龄增加而增加。在1-5岁(平均年龄为2.9岁)之间的对照受试者中,GH的相对特异性结合为37.0 /-2.0%(平均水平/-SEM),而在年轻人(平均年龄)中逐渐增加至93.0 /-7.0% ,23年)。侏儒血清中GH的相对特异性结合在任何年龄段均不超过对照成人标准的30.1 /-3.4%(P小于0.001),并且与年龄相关的结合没有进行性增加。在侏儒时期,正常binding缩的减少极少(29%),但在青少年和成人中,binding缩比正常的减少为60-70%。因此,侏儒矮小可能不是由于GH受体本身的绝对缺乏(如Laron侏儒症),而是由于细胞GH受体不能以正常方式增加。这与调节GH受体基因表达的变化最相容,而不是与GH受体基因编码序列的结构缺陷最相容。
  • 【研究一种标准的乞力士成分混合粉的生产,理化和感官特性。】 复制标题 收藏 收藏
    DOI:10.3109/09637489709012589 复制DOI
    作者列表:Badau MH,Igene JO,Collison EK,Nkama I
    BACKGROUND & AIMS: :The quality of kilishi, a sun dried roasted meat product vary considerably due to lack of consistent standardized non meat ingredient portion (spices and condiments) used for its preparation. In this study, an instant standard kilishi ingredient mix powder was developed. The mix powder contained 9.1% moisture, 49.7% protein, 8.3% fat, 3.2% fibre, and 4.4% ash. Particle size of the mix developed was finer than the traditional one. Yield of kilishi increased with increasing concentration of the standard mix powder used for infusion. The highest yield (87%) was obtained at 60% slurry concentration of the mix compared to 59% yield when the traditional paste was used for infusion. Sensory attributes of kilishi produced using 60% slurry concentration of the standard mix was rated better than a commercial kilishi product (P < 0.05).
    背景与目标: :由于干燥时缺乏一致的标准化非肉类成分(香料和调味品),乞力士(晒干的烤肉产品)的质量差异很大。在这项研究中,开发了一种即时标准的乞力士成分混合粉。混合粉末含有9.1%的水分,49.7%的蛋白质,8.3%的脂肪,3.2%的纤维和4.4%的灰分。所开发混合物的粒度比传统混合物要细。随着用于输注的标准混合粉浓度的增加,乞力士的产量增加。当混合物的浆液浓度为60%时,最高的收率(87%)获得了回报,而传统糊剂用于灌输时的收率为59%。使用60%的标准混合物浆液浓度产生的乞力士的感官属性等级优于商业乞力士产品(P <0.05)。
  • 【在两项队列研究中,维生素D的摄入量和胰腺癌的风险。】 复制标题 收藏 收藏
    DOI:10.1158/1055-9965.EPI-06-0206 复制DOI
    作者列表:Skinner HG,Michaud DS,Giovannucci E,Willett WC,Colditz GA,Fuchs CS
    BACKGROUND & AIMS: :Vitamin D and its analogues exhibit potent antitumor effects in many tissues, including the pancreas. Normal and malignant pancreatic tissues were recently shown to express high levels of vitamin D 1-alpha-hydroxylase, which converts circulating 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. We examined associations between dietary intake of vitamin D, calcium, and retinol and subsequent risk for pancreatic cancer. We conducted prospective studies in cohorts of 46,771 men ages 40 to 75 years as of 1986 (the Health Professionals Follow-up Study), and 75,427 women ages 38 to 65 years as of 1984 (the Nurses' Health Study), documenting incident pancreatic cancer through the year 2000. Diet was ascertained by semiquantitative food-frequency questionnaire. We identified 365 incident cases of pancreatic cancer over 16 years of follow-up. Compared with participants in the lowest category of total vitamin D intake (<150 IU/d), pooled multivariate relative risks for pancreatic cancer were 0.78 [95% confidence interval (95% CI), 0.59-1.01] for 150 to 299 IU/d, 0.57 (95% CI, 0.40-0.83) for 300 to 449 IU/d, 0.56 (95% CI, 0.36-0.87) for 450 to 599 IU/d, and 0.59 (95% CI, 0.40-0.88) for >/=600 IU/d (P(trend) = 0.01). These associations may be stronger in men than women. After adjusting for vitamin D intake, calcium and retinol intakes were not associated with pancreatic cancer risk. In two U.S. cohorts, higher intakes of vitamin D were associated with lower risks for pancreatic cancer. Our results point to a potential role for vitamin D in the pathogenesis and prevention of pancreatic cancer.
    背景与目标: 维生素D及其类似物在包括胰腺在内的许多组织中均显示出强大的抗肿瘤作用。最近显示正常和恶性胰腺组织表达高水平的维生素D1-α-羟化酶,可将循环中的25-羟基维生素D转化为活性1,25-二羟基维生素D。视黄醇和随后的胰腺癌风险。截至1986年,我们对46,771名40-75岁的男性(健康专业人员随访研究)和75,427名38-65岁的女性(队列1984年)(护士健康研究)进行了前瞻性研究,记录了胰腺癌的发生情况。到2000年。通过半定量食物频率问卷确定饮食。在16年的随访中,我们确定了365例胰腺癌事件病例。与总维生素D摄入量最低的类别(<150 IU / d)的参与者相比,胰腺癌的汇总多元相对风险为0.78 [95%置信区间(95%CI),0.59-1.01],范围为150至299 IU / d,对于300至449 IU / d为0.57(95%CI,0.40-0.83),对于450至599 IU / d为0.56(95%CI,0.36-0.87),对于0.59(95%CI,0.40-0.88) > / = 600 IU / d(P(趋势)= 0.01)。这些联系在男性中可能比女性更强。在调整了维生素D的摄入量之后,钙和视黄醇的摄入量与胰腺癌的风险无关。在美国的两个队列中,维生素D的摄入量增加与胰腺癌的风险降低有关。我们的研究结果表明维生素D在胰腺癌的发病机理和预防中的潜在作用。

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