• 【前列腺癌放疗四种靶对准方法的剂量学比较。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijrobp.2006.06.044 复制DOI
    作者列表:O'Daniel JC,Dong L,Zhang L,de Crevoisier R,Wang H,Lee AK,Cheung R,Tucker SL,Kudchadker RJ,Bonnen MD,Cox JD,Mohan R,Kuban DA
    BACKGROUND & AIMS: PURPOSE:The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS:During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (US), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the metric for target coverage. RESULTS:Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. CONCLUSIONS:Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate.
    背景与目标:
  • 【含咖啡因补充剂对力量,肌肉耐力和无氧能力的急性影响。】 复制标题 收藏 收藏
    DOI:10.1519/18285.1 复制DOI
    作者列表:Beck TW,Housh TJ,Schmidt RJ,Johnson GO,Housh DJ,Coburn JW,Malek MH
    BACKGROUND & AIMS: :The purpose of this study was to examine the acute effects of a caffeine-containing supplement on upper- and lower-body strength and muscular endurance as well as anaerobic capabilities. Thirty-seven resistance-trained men (mean +/- SD, age: 21 +/- 2 years) volunteered to participate in this study. On the first laboratory visit, the subjects performed 2 Wingate Anaerobic Tests (WAnTs) to determine peak power (PP) and mean power (MP), as well as tests for 1 repetition maximum (1RM), dynamic constant external resistance strength, and muscular endurance (TOTV; total volume of weight lifted during an endurance test with 80% of the 1RM) on the bilateral leg extension (LE) and free-weight bench press (BP) exercises. Following a minimum of 48 hours of rest, the subjects returned to the laboratory for the second testing session and were randomly assigned to 1 of 2 groups: a supplement group (SUPP; n = 17), which ingested a caffeine-containing supplement, or a placebo group (PLAC; n = 20), which ingested a cellulose placebo. One hour after ingesting either the caffeine-containing supplement or the placebo, the subjects performed 2 WAnTs and were tested for 1RM strength and muscular endurance on the LE and BP exercises. The results indicated that there was a significant (p < 0.05) increase in BP 1RM for the SUPP group, but not for the PLAC group. The caffeine-containing supplement had no effect, however, on LE 1RM, LE TOTV, BP TOTV, PP, and MP. Thus, the caffeine-containing supplement may be an effective supplement for increasing upper-body strength and, therefore, could be useful for competitive and recreational athletes who perform resistance training.
    背景与目标: : 这项研究的目的是检查含咖啡因补充剂对上半身和下半身力量,肌肉耐力以及无氧能力的急性影响。37名接受过抵抗训练的男性 (平均/- SD,年龄: 21/- 2岁) 自愿参加了这项研究。在第一次实验室访问时,受试者进行了2次Wingate厌氧测试 (想要) 以确定峰值功率 (PP) 和平均功率 (MP),以及1次重复最大值 (1RM),动态恒定外阻力强度和肌肉耐力 (TOTV; 在双侧腿部伸展 (LE) 和自由重量卧推 (BP) 练习的耐力测试中,重量的总体积为1RM的80%。休息至少48小时后,受试者返回实验室进行第二次测试,并被随机分配到2组中的1组: 补充剂组 (SUPP; n = 17),摄入含咖啡因补充剂,或安慰剂组 (PLAC; n = 20),摄入纤维素安慰剂。摄入含咖啡因补充剂或安慰剂一小时后,受试者进行了2次想要,并在LE和BP锻炼中测试了1RM力量和肌肉耐力。结果表明,SUPP组的BP 1RM显着增加 (p <0.05),而PLAC组则没有。但是,含咖啡因的补充剂对LE 1RM,LE TOTV,BP TOTV,PP和MP没有影响。因此,含咖啡因的补充剂可能是增加上身力量的有效补充剂,因此对于进行阻力训练的竞技和休闲运动员可能有用。
  • 【听力下降的听众的语音掩蔽释放: 掩蔽率对识别分数和语音特征接收的影响。】 复制标题 收藏 收藏
    DOI:10.1080/14992020600753213 复制DOI
    作者列表:Lorenzi C,Husson M,Ardoint M,Debruille X
    BACKGROUND & AIMS: :Consonant identification was measured for a stationary and amplitude-modulated noise masker in four listeners with flat cochlear hearing loss, and four age-matched normal-hearing listeners. The masker modulation rate was systematically varied between 2 and 128 Hz. Masking release (MR), that is better identification performance in fluctuating, than in stationary noise, was highest in a masker fluctuating at 8-16 Hz in all normal-hearing listeners. In comparison, MR was only observed in two out of the four impaired listeners. In these listeners, MR was poorer than normal, and peaked at lower rates, that is 2 or 8 Hz. MR corresponded to increased reception of information for voicing, place, and manner between 2 and 64 Hz in all normal-hearing listeners. In impaired listeners, increased reception of information was mainly observed for manner, and mainly reduced for place, but these differences were not significant. For all phonetic features, MR was observed at lower masker fluctuation rates (< or =32 Hz) than in normal-hearing listeners. This study therefore shows that cochlear damage affects MR, both quantitatively and qualitatively.
    背景与目标: : 在四个患有扁平耳蜗听力损失的听众和四个年龄匹配的正常听力听众中,测量了固定和幅度调制的噪声masker的辅音识别。掩蔽器调制速率在2和128Hz之间系统地变化。在所有正常听力的听众中,掩蔽释放 (MR) 在波动中比在固定噪声中更好的识别性能,在8-16Hz波动的掩蔽器中最高。相比之下,仅在四个受损听众中的两个中观察到MR。在这些听众中,MR比正常人差,并且以较低的速率 (即2或8Hz) 达到峰值。MR对应于所有正常听力的听众在2到64Hz之间的发声,位置和方式的信息接收增加。在受损的听众中,主要观察到方式的信息接收增加,而地点的信息接收则主要减少,但这些差异并不显着。对于所有语音特征,与正常听力的听众相比,以较低的掩蔽率 (<或 = 32Hz) 观察到MR。因此,这项研究表明,耳蜗损伤在定量和定性上都会影响MR。
  • 【数学与语言处于同一侧吗?右半球失语症和数学能力。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2006.07.063 复制DOI
    作者列表:Semenza C,Delazer M,Bertella L,Granà A,Mori I,Conti FM,Pignatti R,Bartha L,Domahs F,Benke T,Mauro A
    BACKGROUND & AIMS: :The main purpose of the present study was to learn how mathematical abilities are located and develop in the brain with respect to language. Mathematical abilities were assessed in six right-handed patients affected by aphasia following a lesion to their non-dominant hemisphere (crossed aphasia) and in two left-handed aphasics with a right-sided lesion. Acalculia, although in different degrees, was found in all cases. The type of acalculia depended on the type of aphasia, following patterns that have been previously observed in the most common aphasias resulting from left hemisphere lesions. No sign of right hemisphere or spatial acalculia (acalculia in left lateralised right-handed subjects) was detected. These results suggest that, as a rule, language and calculation share the same hemisphere. A primitive computational mechanism capable of recursion may be the precursor of both functions.
    背景与目标: : 本研究的主要目的是了解语言在大脑中如何定位和发展数学能力。在六名非优势半球病变 (交叉失语症) 后受失语症影响的右手患者和两名右侧病变的左手失语症患者中评估了数学能力。尽管在不同程度上,但在所有情况下都发现了Acalculia。Aalculia的类型取决于失语症的类型,遵循先前在左半球病变引起的最常见失语症中观察到的模式。未检测到右半球或空间无alculia (左侧右手受试者中的无alculia) 的迹象。这些结果表明,通常,语言和计算具有相同的半球。能够递归的原始计算机制可能是这两个功能的前身。
  • 【数字和空间的共享空间表示: SNARC和Simon效应的逆转。】 复制标题 收藏 收藏
    DOI:10.1037/0096-1523.32.5.1197 复制DOI
    作者列表:Notebaert W,Gevers W,Verguts T,Fias W
    BACKGROUND & AIMS: :In 4 experiments, the authors investigated the reversal of spatial congruency effects when participants concurrently practiced incompatible mapping rules (J. G. Marble & R. W. Proctor, 2000). The authors observed an effect of an explicit spatially incompatible mapping rule on the way numerical information was associated with spatial responses. The authors also observed an effect of an incompatible numerical mapping rule (if smaller than 5, press right; if larger than 5, press left) on the Simon effect. This effect was observed only when both tasks used the same effectors. The results point to a shared spatial representation for explicit spatial information (locations) and implicit spatial information (numbers).
    背景与目标: : 在4个实验中,作者研究了参与者同时实践不兼容映射规则时空间一致性效应的逆转 (J. G. Marble & R. W. Proctor,2000)。作者观察到明确的空间不兼容映射规则对数字信息与空间响应相关联的方式的影响。作者还观察到不兼容的数值映射规则 (如果小于5,则按右; 如果大于5,则按左) 对Simon效果的影响。仅当两个任务使用相同的效应器时才观察到这种效果。结果指向显式空间信息 (位置) 和隐式空间信息 (数字) 的共享空间表示。
  • 【老年抑郁症的结构神经影像学研究方法。】 复制标题 收藏 收藏
    DOI:10.1097/01.JGP.0000238588.34205.bd 复制DOI
    作者列表:Hoptman MJ,Gunning-Dixon FM,Murphy CF,Lim KO,Alexopoulos GS
    BACKGROUND & AIMS: :Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, there is evidence that abnormalities in specific brain structures and their interconnections confer vulnerability to the development of late-life depression. Structural magnetic resonance imaging methods can be used to identify and quantify brain abnormalities predisposing to geriatric depression and in prediction of treatment response. This article reviews several techniques, including morphometric approaches, study of white matter hyperintensities, diffusion tensor imaging, magnetization transfer imaging, t2 relaxography, and spectroscopy, that have been used to examine these brain abnormalities with a focus on the type of information obtained by each method as well as each method's limitations. The authors argue that the available methods provide complementary information and that, when combined judiciously, can increase the knowledge gained from neuroimaging findings and conceptually advance the field of geriatric depression.
    背景与目标: : 老年抑郁症由复杂和异质的行为组成,不太可能由单个脑部病变引起。然而,有证据表明,特定大脑结构及其相互联系的异常使人们容易患上晚期抑郁症。结构磁共振成像方法可用于识别和量化易患老年抑郁症的脑部异常,并预测治疗反应。本文回顾了几种技术,包括形态计量学方法,白质高强度研究,扩散张量成像,磁化转移成像,t2弛豫成像和光谱学,这些技术已用于检查这些大脑异常,重点是获得的信息类型通过每种方法以及每种方法的局限性。作者认为,可用的方法提供了补充信息,并且如果明智地结合在一起,可以增加从神经影像学发现中获得的知识,并在概念上推进老年抑郁症领域。
  • 【使用部分重建与完全重建的高分辨率肺CT对运动伪影和图像噪声的影响。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.05.0852 复制DOI
    作者列表:Ha HI,Goo HW,Seo JB,Song JW,Lee JS
    BACKGROUND & AIMS: OBJECTIVE:The purpose of our study was to evaluate the effects of 0.3-second high-resolution CT (HRCT) of the lung using partial reconstruction on cardiac motion artifacts and image noise. SUBJECTS AND METHODS:Thirty-seven pairs of 0.3-second (partial reconstruction) and 0.75-second (full reconstruction) HRCT images were obtained for the lower lung zone during full-inspiration breath-holding. Imaging parameters other than temporal resolution were identical for each patient. Two radiologists visually graded motion artifacts of the cardiac border, bronchi, pulmonary vessels, and fissure in the left lung on a 4-point scale (with 4 indicating no artifacts). The maximum width of motion along the left cardiac border and the area percentage of motion artifacts in the left lung were calculated. Image noise in the air and lung was also determined. Cardiac motion artifacts and image noises were compared between the two sets of CT images. RESULTS:Visual grades for the cardiac border (4 +/- 0), bronchi (3.8 +/- 0.7), pulmonary vessels (3.6 +/- 0.8), and fissure (3.9 +/- 0.5) were higher for 0.3-second images than for 0.75-second images (1.7 +/- 0.7, 2.0 +/- 1.0, 1.6 +/- 0.7, and 2.4 +/- 0.9, respectively) (p < 0.001). The maximum width of motion along the left cardiac border (0.1 +/- 0.5 mm) and the area percentage of motion artifacts in the left lung (6.7% +/- 18.4%) were smaller for 0.3-second images than for 0.75-second images (4.5 +/- 1.7 mm and 36.2% +/- 20.9%, respectively) (p < 0.001). Image noises in the air (38.0 +/- 9.2) and the lung (86.0 +/- 23.1) were greater for 0.3-second images than for 0.75-second images (35.6 +/- 9.6 and 76.0 +/- 20.3, respectively) (p < 0.01). CONCLUSION:Compared with 0.75-second HRCT using full reconstruction, 0.3-second HRCT using partial reconstruction substantially reduces cardiac motion artifacts in the lung at the expense of increasing image noise.
    背景与目标:
  • 【吸收氢化酶的调节和氢利用对沼泽红假单胞菌基因表达的影响。】 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: : 红假单胞菌 (Rhodopseudomonas palustris) 是一种紫色的兼性光养细菌,在光自养生长过程中使用氢气作为电子供体进行二氧化碳固定或在固氮过程中进行氨合成。它还使用氢作为电子补充剂,以使氧化的碳化合物 (例如苹果酸盐) 在光异养生长过程中完全同化为细胞材料。R. palustris基因组预测了膜结合的镍铁吸收氢化酶和几种控制氢化酶合成的调节蛋白。还有一个新的传感器激酶基因 (RPA0981) 直接与氢化酶基因簇相邻。在这里,我们显示了R. palustris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的作用很小。我们还确定,两组分系统RegS-RegR抑制了摄取氢化酶的表达,可能是对细胞内氧化还原状态变化的响应。转录组分析表明,与缺乏摄取氢化酶的突变菌株相比,在固氮条件下在苹果酸上光异养生长时利用氢的R. palustris细胞中约30个基因差异表达。由此看来,以氢形式回收还原剂对R. palustris的基因表达没有广泛的非特异性影响。
  • 【大剂量辛伐他汀对SD大鼠前额叶皮层和纹状体多巴胺水平及其再摄取的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2006.09.009 复制DOI
    作者列表:Wang Q,Tang XN,Wang L,Yenari MA,Ying W,Goh BC,Lee HS,Wilder-Smith EP,Wong PT
    BACKGROUND & AIMS: :Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q. Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate dopamine D(1) and D(2) receptor expression in the rat prefrontal cortex: possible involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005) 933-939] and restored its downregulation in a model of Parkinson's disease (PD) [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233]. Here we explore the effects of simvastatin treatment on tissue dopamine content and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10 mg kg(-1)day(-1), p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were taken out for dopamine content and its reuptake. Using high-performance liquid chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1)day(-1)) was found to increase dopamine content by 110% in the striatum but decreased by 76% in the prefrontal cortex compared with the saline treated group. Dopamine (DA) reuptake was unchanged in both brain regions. These results suggest that chronic treatment with high dose of simvastatin may affect DA tissue level in prefrontal cortex and striatum without changing on DA reuptake. This may have important clinical implications in psychiatric and striatal dopaminergic disorders.
    背景与目标: : 他汀类药物越来越多地用于治疗各种疾病,而不仅仅是其降低胆固醇的原始适应症。我们先前报道辛伐他汀增加了大鼠前额叶皮层的多巴胺受体 [Q. Wang,W.L. Ting,H. Yang,P.T. Wong,高剂量辛伐他汀上调大鼠前额叶皮层的多巴胺D(1) 和D(2) 受体表达: 可能参与内皮型一氧化氮合酶,br.J. Pharmacol. 144 (2005) 933-939] 并在帕金森氏病 (PD) 模型中恢复了其下调 [Q. Wang,P.H. Wang,C. McLachlan,P.T. Wong,辛伐他汀可逆转6-羟基多巴胺诱导的帕金森病大鼠前额叶皮层多巴胺D1和D2受体表达的下调,脑Res. 1045 (2005) 229-233]。在这里,我们探讨辛伐他汀治疗对组织多巴胺含量和再摄取的影响。Sprague-Dawley大鼠给予辛伐他汀 (1和10 mg kg(-1) 天 (-1),p.o.) 4周。取出前额叶皮层和纹状体的脑组织以获取多巴胺含量及其再摄取。使用高效液相色谱-质谱仪 (hplc-ms),发现辛伐他汀 (10 mg kg(-1) 天 (-1)) 在纹状体中110% 增加多巴胺含量,但在前额叶皮层中减少76% 与生理盐水治疗组相比。两个大脑区域的多巴胺 (DA) 再摄取均未改变。这些结果表明,高剂量辛伐他汀的慢性治疗可能会影响前额叶皮层和纹状体的DA组织水平,而不会改变DA的再摄取。这可能对精神病和纹状体多巴胺能疾病具有重要的临床意义。
  • 【热休克蛋白-90 (HSP90) 在多发性骨髓瘤中的表达及HSP90抑制剂 (17-AAG) 的作用分析。】 复制标题 收藏 收藏
    DOI:10.1080/10428190500472123 复制DOI
    作者列表:Duus J,Bahar HI,Venkataraman G,Ozpuyan F,Izban KF,Al-Masri H,Maududi T,Toor A,Alkan S
    BACKGROUND & AIMS: :Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.
    背景与目标: : 热休克蛋白90 (HSP90) 是各种蛋白质的结构折叠和构象完整性维持所必需的,包括与细胞信号传导相关的几种。利用HSP90抑制剂17-allylamino-17-demethoxygeldanamycin (17-AAG) 的最新研究表明,在实体瘤中具有抗肿瘤作用。为了测试HSP90是否可以靶向多发性骨髓瘤 (MM) 患者,我们首先通过免疫荧光和流式细胞仪分析研究了HSP90在骨髓瘤细胞系 (U266) 和原发性骨髓瘤细胞中的表达。在证明骨髓瘤细胞中HSP90表达后,通过免疫过氧化物酶染色分析了32 MM患者的档案样本。所有患者的骨髓瘤细胞在所有样品中均显示出HSP90的强细胞质表达,并且55% 还显示出同时的核免疫阳性。与未处理的对照细胞相比,用17AAG处理U266和原代MM细胞可显着增加细胞凋亡。对与17-aag孵育的MM细胞中抗凋亡BCL2家族蛋白和akt的分析表明,BCL-2,BCL-XL,MCL-1和akt下调。此外,尽管低浓度的硼替佐米不会导致细胞死亡,但17AAG和硼替佐米的组合治疗显示出对U266细胞系的协同凋亡作用。这些数据表明,靶向抑制HSP90可能被证明是开发MM患者未来治疗选择的有效且创新的策略。
  • 【B细胞慢性淋巴细胞白血病患者T细胞中的信号分子和细胞因子产生: 氟达拉滨和阿仑单抗治疗的长期影响。】 复制标题 收藏 收藏
    DOI:10.1080/10428190600565503 复制DOI
    作者列表:Kiaii S,Choudhury A,Mozaffari F,Rezvany R,Lundin J,Mellstedt H,Osterborg A
    BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.
    背景与目标: : 氟达拉滨和阿仑单抗通常用于治疗b细胞慢性淋巴细胞白血病 (b-cll)。本研究旨在比较在氟达拉滨或阿仑单抗治疗后长期未维持缓解/平台期的b-cll患者的T细胞与惰性/未治疗的b-cll患者和健康的T细胞的信号分子表达和细胞因子产生供体。通过流式细胞术检查CD4和CD8 T细胞中TCR-CD3zeta链,p56lck,p59fyn,ZAP-70,PI3-kinase和干扰素 (IFN)-γ/白细胞介素 (IL)-4产生的频率和强度。通过纯化蛋白衍生物 (PPD) 和植物血凝素 (PHA) 刺激来评估T细胞功能。尽管数量减少,但患者T细胞中IFN-γ/IL-4的表达显着高于健康供体。与健康供体相比,接受治疗的患者中大多数信号分子的强度相对不受影响,但低于未经治疗的惰性患者。然而,在患者中表达每种信号分子的T细胞总数减少,而氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中,T细胞对PHA的反应降低,但对PPD的反应降低。结果表明,尽管信号分子发生了一些变化,T细胞数量减少,但在用氟达拉滨和阿仑单抗治疗后,总体T细胞功能可能长期保持良好。
  • 【ERCP透皮三硝酸甘油的前瞻性,随机,安慰剂对照试验: 对技术成功和ERCP后胰腺炎的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.gie.2005.11.060 复制DOI
    作者列表:Kaffes AJ,Bourke MJ,Ding S,Alrubaie A,Kwan V,Williams SJ
    BACKGROUND & AIMS: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.
    背景与目标:
  • 【阿片肽对 μ 受体选择性的直接作用: 豚鼠室旁和视上核的细胞内记录。】 复制标题 收藏 收藏
    DOI:10.1016/0306-4522(90)90426-5 复制DOI
    作者列表:Wuarin JP,Dudek FE
    BACKGROUND & AIMS: :Responses to [D-Ala2, MePhe4, Gly-ol5]enkephalin, a selective agonist for mu-receptors, were recorded intracellularly from 26 neurons in slices of guinea-pig hypothalamus. Of eight cells tested in the supraoptic nucleus, all of which had electrical properties characteristic of magnocellular neuroendocrine cells, four were sensitive to the agonist applied in the perfusion bath or with microdrops. The main effect was a decrease or suppression of spontaneous firing. In the paraventricular nucleus, seven of 18 cells tested also had electrophysiological characteristics similar to magnocellular neurons: two of them were sensitive to the mu-agonist and the effect was similar to that observed in the supraoptic nucleus. The remaining paraventricular neurons displayed low-threshold Ca2+ spikes, and thus had electrophysiological characteristics different from putative magnocellular neurons. Ten of 11 cells with low-threshold Ca2+ spikes were hyperpolarized by more than 10 mV by the mu-agonist, and showed a 33 +/- 1.9% (S.E.M.) decrease in input resistance. In both types of cells, when synaptic transmission was blocked with tetrodotoxin, the mu-agonist could still induce a hyperpolarization, suggesting that the effect was in part direct. Hyperpolarization was also obtained when the Cl- reversal potential was shifted to more positive values by using KCl electrodes, thus excluding a Cl- conductance mechanism. These results provide evidence that opioid peptides can directly inhibit hypothalamic neurons, that the mechanism is an increase in K+ conductance, and that two types of hypothalamic neurons appear to have different sensitivities to a mu-agonist.
    背景与目标: : 从豚鼠下丘脑切片中的26个神经元在细胞内记录了对 [D-Ala2,MePhe4,Gly-ol5] 脑啡肽 (mu受体的选择性激动剂) 的反应。在视上核中测试的八个细胞中,所有这些细胞均具有大细胞神经内分泌细胞的电特性,其中四个对灌注浴或微滴中使用的激动剂敏感。主要效果是减少或抑制自发发射。在室旁核中,测试的18个细胞中有7个具有类似于大细胞神经元的电生理特征: 其中两个对mu激动剂敏感,其作用类似于在视上核中观察到的作用。其余的室旁神经元显示出低阈值的Ca2尖峰,因此具有与假定的大细胞神经元不同的电生理特征。具有低阈值Ca2尖峰的11个细胞中的10个被mu激动剂超极化超过10 mV,并显示输入阻力降低了33/- 1.9% (s.e.M.)。在两种类型的细胞中,当河豚毒素阻断突触传递时,mu激动剂仍可诱导超极化,这表明该作用部分是直接的。当使用KCl电极将Cl反转电位移至更多正值时,也获得了超极化,从而排除了Cl电导机制。这些结果提供了证据,表明阿片肽可以直接抑制下丘脑神经元,其机制是K电导的增加,并且两种类型的下丘脑神经元似乎对mu激动剂具有不同的敏感性。
  • 【压力限制通气期间持续气管气吹入对急性肺损伤家兔肺表面活性物质的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Zhu GF,Zhang W,Zong H,Liang Y
    BACKGROUND & AIMS: BACKGROUND:Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (V(T)) while maintaining constant partial arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI). METHODS:ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n = 8 for each group), and subsequently ventilated with limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours. Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS:TGI resulted in significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5 +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T) [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg], SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3) mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02) ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24) mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05 vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS:In this animal model of ALI, TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.
    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:

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