• 【钳位上升时间对非洲爪蟾卵母细胞大鼠脑IIA钠通道的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-0270(96)02216-9 复制DOI
    作者列表:Ruben PC,Fleig A,Featherstone D,Starkus JG,Rayner MD
    BACKGROUND & AIMS: The kinetic properties of wild-type rat brain IIa sodium channels in excised macropatches were studied using step depolarizations and ramp depolarizations to imitate the slow settling-time of voltage in two-electrode voltage clamp. Ramp depolarizations longer than 1 ms produce an increasing suppression of peak sodium current (I[Na]). Two rates of inactivation can be seen in macroscopic sodium current records from excised patches following both step and ramp depolarizations. During slow ramp depolarizations, reduction in peak I[Na] is associated with selective loss of the fastest rate of test-pulse inactivation. This change can be interpreted as resulting from inactivation of a separate sub-population of 'fast mode' channels. The slow rate of test-pulse inactivation is relatively unaffected by changing ramp durations. These results are sufficient to explain the typically slow inactivation kinetics seen in two-electrode voltage clamp recordings of sodium channels in Xenopus oocytes. Thus, the kinetics of sodium channels expressed in Xenopus oocytes are not readily characterizable by two-electrode clamp because of the large membrane capacitance and resulting slow clamp settling time which artifactually selects for slow mode channels.

    背景与目标: 使用逐步去极化和斜坡去极化来模拟两电极电压钳位中电压的缓慢建立时间,研究了切除的大斑块中野生型大鼠脑IIa钠通道的动力学特性。长于1 ms的斜坡去极化会增加对峰值钠电流 (I[Na]) 的抑制。在阶跃和斜坡去极化之后,从切除的斑块的宏观钠电流记录中可以看到两种失活速率。在缓慢的斜坡去极化过程中,峰值I[Na] 的降低与最快的测试脉冲失活速率的选择性损失有关。此更改可以解释为由于 “快速模式” 通道的单独子种群的失活而导致。测试脉冲失活的缓慢速度相对不受斜坡持续时间变化的影响。这些结果足以解释非洲爪蟾卵母细胞中钠通道的两电极电压钳制记录中看到的典型的缓慢失活动力学。因此,非洲爪蟾卵母细胞中表达的钠通道的动力学不容易通过两电极钳来表征,因为膜电容大,并且会导致人为选择慢模式通道而产生的慢钳建立时间。
  • 【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。
  • 【庞贝病骨骼肌自噬和治疗酶的误用。】 复制标题 收藏 收藏
    DOI:10.1016/j.ymthe.2006.08.009 复制DOI
    作者列表:Fukuda T,Ahearn M,Roberts A,Mattaliano RJ,Zaal K,Ralston E,Plotz PH,Raben N
    BACKGROUND & AIMS: :Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic buildup in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target--the lysosomes. A fluid-phase endocytic marker was similarly mistargeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process and point toward new avenues for the development of pharmacological intervention.
    背景与目标: : 酶替代疗法 (ERT) 已成为Pompe病患者的现实,Pompe病是一种致命的心肌病和骨骼肌肌病,该病是由糖原降解溶酶体酶酸 α-葡萄糖苷酶 (GAA) 缺乏引起的。该疗法依赖于重组人GAA (rhGAA) 的受体介导的内吞作用,似乎对心肌有效,但对骨骼肌无效。我们以前已经显示出GAA基因敲除小鼠 (KO) 的抗药性肌肉中溶酶体降解途径 (自噬) 的严重干扰。我们在这里的发现表明,除了在KO的多个肌肉群中增加糖原填充的溶酶体外,还存在逐渐的年龄依赖性自噬积累。治疗酶沿内吞途径的运输和加工似乎受到自噬的影响。暴露于荧光标记的rhGAA的活的单根肌肉纤维的共聚焦显微镜显示,KO中很大一部分内吞酶被捕获为自噬区域中的部分加工形式,而不是达到其目标-溶酶体。类似地,液相内吞标记物被错误地捕获并积累在自噬区域内的囊泡结构中。这些发现可以解释为什么ERT经常无法逆转疾病过程,并为药物干预的发展指明了新的途径。
  • 【克罗恩病的Interleukin-12和Th1免疫反应: 发病相关性和治疗意义。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i35.5606 复制DOI
    作者列表:Peluso I,Pallone F,Monteleone G
    BACKGROUND & AIMS: :Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue-damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL-12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.
    背景与目标: 克罗恩病 (CD) 和溃疡性结肠炎 (UC) 是胃肠道的慢性炎症性疾病,具有共同的临床和病理特征。最受认可的假设是,CD和UC都是由于对肠道微生物群落正常成分的粘膜免疫反应失调所致。然而,有证据表明,这两种疾病的主要病理过程是不同的。在CD中,破坏组织的炎症反应是由激活的1型辅助T细胞 (Th1) 驱动的,而在UC中,体液反应占主导地位。一致地,在CD中观察到产生主要Th1-inducing因子白介素 (IL)-12的巨噬细胞的明显积累,但在UC粘膜中未见。初步研究还表明,施用阻断IL-12/p40亚基的单克隆抗体可用于诱导和维持CD患者的临床缓解。值得注意的是,最近描述的IL-23与IL-12共享p40亚基,这增加了CD中anti-IL-12/p40抗体的临床益处也可能归因于IL-23活性的中和的可能性。这篇综述总结了有关CD患者和结肠炎实验模型中IL-12和IL-12-associated信号通路的表达和功能作用的最新信息,从而强调了IL-12和IL-23活性在肠道炎症发展中的主要差异。
  • 【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掩蔽者的辅音识别。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。
  • 6 Therapeutic targeting of cytokines. 复制标题 收藏 收藏

    【细胞因子的治疗靶向。】 复制标题 收藏 收藏
    DOI:10.1016/j.cyto.2006.07.018 复制DOI
    作者列表:Barnes T,Goodacre J,Moots RJ
    BACKGROUND & AIMS: :Over recent years, with many advances in understanding the pathological processes that underlie many inflammatory conditions, it has become clear that targeting cytokines has proven to be highly effective therapeutically. The second International Cytokine symposium, held recently in Manchester UK, has provided an important forum for bringing basic and clinical scientists together to discuss many aspects of cytokine medicine from the laboratory to the clinic. In this article, we provide an overview of the main issues raised from this important conference and set the scene for more detailed reports that follow in subsequent articles in this journal.
    背景与目标: : 近年来,随着对许多炎症性疾病基础的病理过程的了解的许多进展,很明显,靶向细胞因子已被证明在治疗上非常有效。最近在英国曼彻斯特举行的第二届国际细胞因子研讨会为将基础和临床科学家聚集在一起,讨论从实验室到临床的细胞因子医学的许多方面提供了重要的论坛。在本文中,我们概述了这次重要会议提出的主要问题,并为更详细的报告设置了场景,这些报告将在本期刊的后续文章中进行。
  • 7 Cerebral metastases--a therapeutic update. 复制标题 收藏 收藏

    【脑转移 -- 治疗更新。】 复制标题 收藏 收藏
    DOI:10.1038/ncpneuro0263 复制DOI
    作者列表:Cavaliere R,Schiff D
    BACKGROUND & AIMS: :Cerebral metastases remain a common complication among patients with cancer. Historically, whole-brain radiotherapy has remained the standard of care, with surgery being reserved for selected cases. Recent advances have changed our practice, however. In particular, stereotactic radiosurgery has emerged as a vital treatment modality for this disease. In addition, chemotherapy, including temozolomide, topoisomerase inhibitors and antimetabolites, and treatment sensitizers, such as efaproxiral and motexafin gadolinium, are actively being assessed in clinical trials, and are likely to play an increasing role in the management of cerebral metastases in the future. Nonetheless, many uncertainties remain, such as the optimal combination and timing of therapeutics. As the arsenal of therapeutics expands, it will be increasingly important to select appropriate patients for a particular treatment paradigm. Understanding the efficacy and toxicity of treatment is essential to this task.
    背景与目标: : 脑转移仍然是癌症患者的常见并发症。从历史上看,全脑放疗一直是护理的标准,手术是为选定的病例保留的。然而,最近的进展改变了我们的做法。特别是,立体定向放射外科已成为该疾病的重要治疗方式。此外,化疗,包括替莫唑胺、拓扑异构酶抑制剂和抗代谢物,以及治疗敏化剂,如efaproxiral和motexafin钆,正在临床试验中积极评估,并可能在未来脑转移的管理中发挥越来越大的作用。尽管如此,仍然存在许多不确定性,例如治疗的最佳组合和时机。随着治疗学库的扩展,为特定的治疗范例选择合适的患者将变得越来越重要。了解治疗的疗效和毒性对于这项任务至关重要。
  • 【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。
  • 【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:
  • 【关节内高分子量透明质酸注射治疗非减少颞下颌关节盘移位的短期治疗结果。】 复制标题 收藏 收藏
    DOI:10.1016/j.tripleo.2005.09.018 复制DOI
    作者列表:Yeung RW,Chow RL,Samman N,Chiu K
    BACKGROUND & AIMS: :In a patient with temporomandibular disorder who does not respond to conservative treatment, treatment with intra-articular injection of high molecular weight sodium hyaluronate can be suggested. In our study, 27 patients with nonreduced disc displacement were diagnosed clinically and confirmed by magnetic resonance imaging. The age range was from 21 to 63 years old, with a mean of 39.3 years. Two cycles of injection of high molecular weight sodium hyaluronate was performed on alternative weeks. Pain intensity was measured by the visual analog scale. Maximal mouth opening, clicking joint noise, and lateral movement were measured before and after injection for more than 6 months. Reduction of pain intensity and improvement in the maximum mouth opening parameter was statistically significant. In conclusion, this intra-articular injection using high molecular weight sodium hyaluronate looks very positive for patients affected by nonreduced disc displacement and is encouraged to be used as a primary treatment of temporomandibular joint dysfunction.
    背景与目标: : 对于对保守治疗无反应的颞下颌疾病患者,建议使用关节内注射高分子量透明质酸钠进行治疗。在我们的研究中,临床诊断出27例椎间盘移位未减少的患者,并通过磁共振成像证实。年龄范围为21至63岁,平均39.3岁。在其他星期进行了两个周期的高分子量透明质酸钠注射。疼痛强度通过视觉模拟量表测量。注射前后6个月以上,测量最大张口,点击关节噪声和侧向运动。疼痛强度的降低和最大张口参数的改善具有统计学意义。总之,这种使用高分子量透明质酸钠的关节内注射对于受椎间盘移位不全影响的患者看起来非常积极,并被鼓励用作颞下颌关节功能障碍的主要治疗方法。
  • 【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,超出了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了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患者的信号分子表达和细胞因子产生和健康供体。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。

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