BACKGROUND & AIMS: :Oral tolerance, an important feature of the mucosal immune system, appears to protect against immune-mediated disease by blunting production of systemic IgG and IgM antibody directed toward immunogens chronically present at mucosal surfaces. In this study, we explored the role of oral tolerance and mucosal immunoregulation in an experimental model of IgA nephropathy (IgAN), an important form of nephritis in humans. Cyclophosphamide and estradiol were used to inhibit the expression of oral tolerance, which otherwise develops after chronic oral presentation of Ag. BALB/c mice given drinking water containing 0.1% bovine gamma globulin (BGG) continuously for 14 wk were randomly assigned to groups given either 2 mg of cyclophosphamide i.p., 2 mg of estradiol s.c. or both drugs. Groups of control mice received neither BGG nor drugs. In three separate experiments, a low percentage of saline-treated orally immunized mice had microscopic hematuria (0 to 20%), as did nonimmunized controls (0 to 20%). However, 58 to 83% of mice given estradiol and/or cyclophosphamide at appropriate times developed significant hematuria. If drugs were given at suboptimal times, only 25 to 56% of mice developed hematuria. Drug-treated immunized mice also had more serum IgG and IgM anti-BGG antibodies than control and saline groups. Immunofluorescence showed significantly more glomerular deposits of IgG, IgM, and C3 in drug-treated immunized mice compared to saline-treated immunized and normal untreated control mice. Hematuria and glomerular deposits of IgG, IgM, and C3 paralleled serum IgG and IgM antibody. All immunized mice showed significant mesangial IgA and BGG deposits and there were no differences in such deposits between saline- and drug-treated immunized mice. We suggest that blunting of oral tolerance with promotion of systemic IgG and IgM antibody production leads to nephritis in chronically orally immunized mice and that glomerular immune complexes containing IgG and/or IgM promote complement deposition and hematuria in IgAN. Analogous defects in oral (or more generally mucosal) tolerance could play a role in the genesis of symptomatic human IgAN.

背景与目标： ：口腔耐受是粘膜免疫系统的一个重要特征，它似乎通过减弱针对长期存在于粘膜表面的免疫原的全身性IgG和IgM抗体的产生，来保护自身免受免疫介导的疾病的侵害。在这项研究中，我们探讨了口服耐受性和粘膜免疫调节在IgA肾病（IgAN）（一种人类肾炎的重要形式）实验模型中的作用。环磷酰胺和雌二醇被用来抑制口腔耐受性的表达，否则这种耐受性会在长期口服Ag后发展。连续14周连续喝含0.1％牛γ-球蛋白（BGG）的饮用水的BALB / c小鼠被随机分为两组，分别给予2 mg环磷酰胺i.p.，2 mg雌二醇s.c.或同时使用这两种药物。对照组小鼠既不接受BGG也不接受药物。在三个独立的实验中，经盐水处理的经口免疫小鼠中有低百分比的患者出现镜下血尿（0％至20％），而未免疫的对照小鼠则为0％至20％。但是，在适当的时间接受雌二醇和/或环磷酰胺的小鼠中有58％至83％出现了明显的血尿。如果在最适时的时间使用药物，则只有25％到56％的小鼠会出现血尿。药物治疗的免疫小鼠也比对照组和生理盐水组具有更多的血清IgG和IgM抗BGG抗体。免疫荧光显示与盐水处理的免疫小鼠和正常未处理的对照小鼠相比，在药物处理的免疫小鼠中IgG，IgM和C3的肾小球沉积明显更多。血尿和IgG，IgM和C3的肾小球沉积物与血清IgG和IgM抗体平行。所有免疫的小鼠均显示出明显的系膜IgA和BGG沉积物，并且在盐水和药物处理的免疫小鼠之间，此类沉积物没有差异。我们建议通过口服全身免疫的小鼠促进全身性IgG和IgM抗体产生的口服耐受性减退会导致肾炎，而含有IgG和/或IgM的肾小球免疫复合物会促进IgAN中的补体沉积和血尿。口腔（或更常见的粘膜）耐受性的类似缺陷可能在有症状的人类IgAN的发生中起作用。

BACKGROUND & AIMS: :The authors report an unconventional method of management in hematomas complicating tangentiel trauma. They use the application of liposuction within the first days, this procedure allow complete removal of the clots. It is associated with a biological glue sprayed all over the skin detachment. This simple operative technique is carried out under local anaesthesia and minimizes the recurrence of hematoma. The long term morphological result is satisfactory, avoiding the sequelae of conventional procedures.

背景与目标： ：作者报告了一种复杂的切线创伤性血肿的非常规治疗方法。他们在开始的几天内使用吸脂的方法，该程序可以完全清除血块。它与整个皮肤脱落处喷洒的生物胶有关。这种简单的手术技术是在局部麻醉下进行的，可最大程度地减少血肿的复发。长期的形态学结果令人满意，避免了常规程序的后遗症。

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的补充剂对上，下半身的力量，肌肉耐力以及无氧能力的急性作用。三十七名经过抗性训练的男性（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中，受试者进行了2次Wingate无氧测试（WAnT），以确定峰值功率（PP）和平均功率（MP），以及1次重复最大值（1RM），动态恒定的外部阻力强度和肌肉的测试耐力（TOTV；在耐力测试中以1RM的80％进行测试时提升的总重量）在双腿伸展（LE）和自由重量卧推（BP）锻炼中。至少休息48小时后，受试者返回实验室进行第二次测试，并随机分为2组中的1组：补充组（SUPP; n = 17），摄入含咖啡因的补充剂，或服用纤维素安慰剂的安慰剂组（PLAC； n = 20）。摄入含咖啡因的补充剂或安慰剂一小时后，受试者进行了2次WAnT，并在LE和BP锻炼中测试了1RM强度和肌肉耐力。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无作用。因此，含咖啡因的补充剂可能是增加上半身力量的有效补充剂，因此对进行阻力训练的竞技和休闲运动员有用。

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： ：在四个平直的人工耳聋听力下降的听众和四个年龄相匹配的正常听力的听众中，对平稳和调幅的噪声掩蔽器的辅音识别进行了测量。掩蔽调制率在2到128 Hz之间系统地变化。在所有正常听力的听众中，以8-16 Hz波动的掩蔽器中，掩蔽释放（MR）的波动性要好于平稳噪声，这在静态噪声中具有更好的识别性能。相比之下，只有四个受损听者中有两个观察到了MR。在这些听众中，MR比正常人差，并且以较低的频率（即2或8 Hz）达到峰值。 MR对应于在所有正常听力的收听者中2至64 Hz之间的声音，位置和方式信息接收的增加。在听力受损的听众中，主要是通过方式观察到了信息接收的增加，而对于场所则主要是观察到的减少，但是这些差异并不明显。对于所有的语音特征，与正常听力的听众相比，在较低的掩蔽者波动率（<或= 32 Hz）下观察到了MR。因此，这项研究表明，耳蜗损害在数量和质量上都影响MR。

BACKGROUND & AIMS: :This study aimed to clarify the effectiveness of post-operative oral care, including tooth brushing, denture cleaning and tongue cleaning, after digestive tract surgery. Subjects included 30 elderly patients aged 60-98 years (74.9 +/- 7.8 years) who underwent digestive tract surgery. Subjects were randomly divided into an intervention group and a control group. In the intervention group, the following oral care was provided daily over a 5-min period in the morning starting at baseline (day of surgery) and continued for 5 days: gargling with povidone iodine, tooth brushing, denture cleaning using a special brush and tongue cleaning using a tongue brush. In the control group, the subjects only gargled with povidone iodine. We compared the following variables between the two groups at baseline and 5 days later: the sensation of dry mouth, intra-oral gas concentration, pulmonary sounds, body temperature and bacterial flora. The number of patients with abnormal pulmonary sounds (dry or moist rales) increased from 1 to 2 in the intervention group and from 0 to 4 in the control group (P < 0.05). The average number of bacterial species per subject for the control group was 3.64 +/- 1.34 pre-operatively and 3.50 +/- 1.74 post-operatively, whereas that for the intervention group was 3.08 +/- 0.95 pre-operatively and 2.62 +/- 0.65 post-operatively. In the intervention group, there was a significant decrease in the number of bacterial species (P < 0.05). These findings indicate that post-operative oral care in elderly patients undergoing digestive tract surgery lowers the number of bacterial species found in the oral cavity. This effect, in turn, might improve respiratory function.

背景与目标： ：这项研究旨在阐明消化道手术后口腔清洁的有效性，包括刷牙，义齿清洁和舌头清洁。受试者包括接受消化道手术的30位年龄在60-98岁（74.9 /-7.8岁）的老年患者。将受试者随机分为干预组和对照组。在干预组中，每天从基线（手术日）开始，在每天的5分钟内，每天进行以下口腔护理，并持续5天：用聚维酮碘漱口，刷牙，使用专用刷子清洁义齿和使用舌刷清洁舌头。在对照组中，受试者仅含聚维酮碘。我们在基线和5天后比较了两组之间的以下变量：口干的感觉，口内气体浓度，肺音，体温和细菌菌群。在干预组中，肺音异常（干音或湿音）的患者数量从1增加到2，对照组从0增加到4（P <0.05）。对照组术前平均细菌种类为3.64 /-1.34，术后为3.50 /-1.74，而干预组术前为3.08 /-0.95，术后为2.62 /-0.65。操作上。在干预组中，细菌种类的数量显着减少（P <0.05）。这些发现表明，接受消化道手术的老年患者的术后口腔护理降低了在口腔中发现的细菌种类的数量。反过来，这种效果可能会改善呼吸功能。

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学习关于语言的数学能力如何在大脑中定位和发展。评估了六名右撇子患者在非优势性半球病变（交叉性失​​语症）后患失语症的数学能力，以及两名左撇子右手病变的数学能力。在所有情况下均发现失语症，尽管程度不同。失语症的类型取决于失语症的类型，其遵循先前在左半球病变导致的最常见失语症中观察到的模式。未检测到右半球或空间失聪的迹象（左外侧右手受试者的眼球积水）。这些结果表明，通常，语言和计算共享相同的半球。能够递归的原始计算机制可能是这两种功能的先驱。

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练习不兼容的映射规则时空间一致性效果的逆转（J. G. Marble和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字映射规则（如果小于5，请按向右；如果大于5，请按向左）对西蒙效果的影响。仅当两个任务使用相同的效应器时，才观察到这种效果。结果指向用于显式空间信息（位置）和隐式空间信息（数字）的共享空间表示。

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： 目的：本研究的目的是通过部分重建对心脏运动伪影和图像噪声的效果，评估0.3秒高分辨率肺部CT（HRCT）的影响。
研究对象和方法：在全屏吸气时，获得了37对0.3秒（部分重建）和0.75秒（完全重建）的HRCT图像，用于下肺区。对于每个患者，除时间分辨率以外的成像参数均相同。两位放射科医生对心脏边界，支气管，肺血管和左肺裂的运动伪影进行了4分制的视觉分级（其中4表示无伪影）。计算沿左心脏边界的最大运动宽度和左肺中运动伪影的面积百分比。还确定了空气和肺中的图像噪声。比较两组CT图像之间的心脏运动伪影和图像噪声。
结果：0.3秒图像的心脏边界（4 /-0），支气管（3.8 /-0.7），肺血管（3.6 /-0.8）和裂痕（3.9 /-0.5）的视觉等级高于0.75秒图像（分别为1.7 /-0.7、2.0 /-1.0、1.6 /-0.7和2.4 /-0.9）（p <0.001）。对于0.3秒的图像，沿左心脏边界的最大运动宽度（0.1 /-0.5 mm）和左肺中的运动伪影的面积百分比（6.7％/-18.4％）小于0.75秒的图像（分别为4.5±1.7毫米和36.2％±20.9％（p <0.001）。对于0.3秒的图像，空气（38.0 /-9.2）和肺（86.0 /-23.1）的图像噪声大于0.75秒的图像噪声（分别为35.6 /-9.6和76.0 /-20.3）（p <0.01 ）。
结论：与使用完全重建的0.75秒HRCT相比，使用部分重建的0.3秒HRCT可以显着减少肺部的心脏运动伪影，但会增加图像噪声。

BACKGROUND & AIMS: :Passive immunity against gastrointestinal infections has recently been successfully applied as prophylaxis and therapy in patients in a variety of virally and bacterially induced infections. Campylobacter jejuni is frequently associated with acute diarrhoea in humans, and several species of animals have been shown to transmit the disease, although birds have been implicated as the main source of infection. We used bovine and chicken immunoglobulin preparations from the milk and eggs, respectively, of immunized animals for prophylactic and therapeutic treatment of chickens infected with C. jejuni. A marked prophylactic effect (a >99% decrease in the number of bacteria) was noted using either antibody preparation, whereas the therapeutic efficacy, i.e. when antibodies were given after the infection was established, was distinctly lower (80-95%) as judged by faecal bacterial counts. These observations may serve as a starting point for experiments aimed at elimination of the infection in an industrial or farm setting. It may also encourage future attempts to treat, prophylactically or therapeutically, patients with Campylobacter-induced diarrhoea.

背景与目标： ：最近，针对胃肠道感染的被动免疫已成功应用于各种病毒和细菌引起的感染的预防和治疗中。空肠弯曲菌常与人类急性腹泻有关，尽管鸟类被认为是主要的感染源，但已显示出几种动物可传播这种疾病。我们分别使用免疫动物的牛奶和鸡蛋中的牛和鸡免疫球蛋白制剂对空肠弯曲杆菌感染的鸡进行预防和治疗。两种抗体制剂均具有显着的预防作用（细菌数量减少> 99％），而判断的治疗效果（即在感染确定后给予抗体）则明显较低（80-95％）通过粪便细菌计数。这些观察结果可作为旨在消除工业或农场感染的实验的起点。它还可能鼓励将来尝试预防性或治疗性弯曲杆菌引起的腹泻患者。

BACKGROUND & AIMS: :A 29-year-old man was admitted to our institution 10 days after he had undergone an urgent exploratory laparotomy at a local army hospital after a terrorist bombing attack. On admission, deep second-degree and third-degree burns involving 25% of the upper and lower extremities were present, together with a 25 x 10-cm abdominal full-thickness blast injury defect on the left side, an infected eviscerated midline incision, and a colostomy on the right side of the abdomen. The patient underwent a second laparotomy, at which time the intraabdominal abscess was drained, and the abdominal cavity was irrigated with saline. A jejunal perforation was found and sutured. The abdominal cavity was left open and covered with a Bogota bag for temporary closure. On postburn day 18, the patient underwent débridment and grafting of the third-degree burns to the left and right arm and right lower extremities. After several débridment sessions (postburn days 16, 18, 20, 22, and 24), an abdominal skin release and reapproximation were performed (postburn day 26). On postburn day 36, split-thickness skin grafts were placed directly on the granulated tissue of the intestines and on a defect in the left flank and iliac regions. Postoperatively, the patient did well. He was discharged on postburn day 78 with all wounds well healed. In our opinion, temporary closure followed by direct application of meshed split-thickness skin grafts to exposed abdominal viscera represents a simple method of reconstruction that can be safely performed, with minimal risk, on critically ill patients.

背景与目标： ：一名29岁的男子在恐怖炸弹袭击后在当地一家军队医院接受紧急探索性剖腹手术10天后被送进我们的机构。入院时出现上，下肢深部烧伤，累及上肢和下肢的25％，左侧有25 x 10-cm的腹部全层爆炸伤缺损，被感染的内脏中线切口，在腹部右侧进行结肠造口术。患者进行了第二次剖腹手术，此时排空了腹腔内脓肿，并用生理盐水冲洗了腹腔。发现并缝合了空肠穿孔。腹腔保持开放并用Bogota袋覆盖以暂时关闭。烧伤后第18天，患者进行了清创术，并在左右臂和右下肢进行了三度烧伤。经过几次清创术后（烧伤后第16、18、20、22和24天），进行了腹部皮肤的释放和重新逼近（烧伤后第26天）。在烧伤后第36天，将切开厚度的皮肤移植物直接放在肠的肉芽组织上以及左侧腹和骨区域的缺损处。术后病人表现良好。烧伤后第78天他已出院，所有伤口均得到了良好治愈。在我们看来，暂时闭合然后直接将网状劈开厚度的皮肤移植物应用于暴露的腹腔内脏代表了一种简单的重建方法，可以对重症患者进行安全且风险最小的重建。

BACKGROUND & AIMS: :Darier disease is an uncommon genodermatosis reflecting defective desmosomal structure and function. The present report details the oral features of a patient with well-characterized Darier disease and reviews current knowledge of the genetic basis of this genodermatosis that can often affect the craniofacial tissues.

背景与目标： ：Darier病是一种罕见的遗传性皮肤病，反映了桥粒结构和功能的缺陷。本报告详细介绍了特征明确的Darier病患者的口腔特征，并回顾了这种遗传皮肤病的遗传基础的当前知识，这种遗传皮肤病通常会影响颅面组织。

BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.

背景与目标： ：Rhodopseudomonas palustris是一种紫色的兼性光养细菌，它利用氢气作为电子供体，在光养植物生长过程中固定二氧化碳，或在固氮过程中合成氨气。它还使用氢作为电子补充剂，以在光异养生长期间将氧化的碳化合物（例如苹果酸）完全同化到细胞材料中。 R. palustris基因组预测膜结合的镍铁摄取氢化酶和几种调节蛋白来控制氢化酶的合成。与氢化酶基因簇直接相邻的还有一个新的传感器激酶基因（RPA0981）。在这里，我们显示帕氏疟原虫调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用，以响应氢气激活氢化酶表达。转录组分析表明，HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统，推定的甲酸盐转运蛋白和谷氨酰胺合成酶的基因的表达。 RPA0981在抑制氢化酶合成方面作用很小。我们还确定了两组分系统RegS-RegR抑制摄取氢化酶的表达，可能是响应细胞内氧化还原状态的变化。转录组分析表明，与缺乏摄取氢酶的突变菌株相比，当在固氮条件下在苹果酸上光异养地生长时，利用氢的Pal。R. palustris细胞中约有30个基因差异表达。由此看来，还原剂以氢的形式的循环利用对R. palustris的基因表达没有广泛的非特异性影响。

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： 他汀类药物已被用于治疗多种疾病，这些症状超出了降低胆固醇的最初指标。我们先前曾报道辛伐他汀会增加大鼠前额叶皮层中的多巴胺受体[Q.王伟丁宏阳黄，辛伐他汀大剂量上调大鼠前额叶皮层中的多巴胺D（1）和D（2）受体表达：可能与内皮一氧化氮合酶Br有关。 J.Pharmacol。 144（2005）933-939]，并在帕金森氏病（PD）模型中恢复了其下调[Q.王凤华Wang C.McLachlan，P.T. Wong，辛伐他汀逆转了6-羟基多巴胺诱导的帕金森病大鼠Brain Res的前额叶皮层中多巴胺D1和D2受体表达的下调。 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大鼠接受辛伐他汀（1和10 mg kg（-1）day（-1），口服）4周。取出前额叶皮层和纹状体的脑组织中的多巴胺含量并重新摄取。使用高效液相色谱质谱仪（HPLC-MS），发现辛伐他汀（10 mg kg（-1）day（-1））在纹状体中可使多巴胺含量增加110％，但在前额叶中减少76％皮层与生理盐水处理组相比。在两个大脑区域中，多巴胺（DA）的再摄取均未改变。这些结果表明，高剂量辛伐他汀的长期治疗可能会影响额叶前额叶皮层和纹状体中的DA组织水平，而不会改变DA的再摄取。这在精神病和纹状体多巴胺能障碍中可能具有重要的临床意义。

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）是结构折叠和维持各种蛋白质（包括与细胞信号相关的几种蛋白质）构象完整性的必需。利用HSP90抑制剂17-烯丙基氨基-17-去甲氧基格尔德霉素（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是否可以靶向于多发性骨髓瘤（MM）患者，我们首先通过免疫荧光和流式细胞术分析了骨髓瘤细胞系（U266）和原发性骨髓瘤细胞中HSP90的表达。在证明HSP90在骨髓瘤细胞中表达后，通过免疫过氧化物酶染色分析了32例MM患者的档案样本。在所有患者中，骨髓瘤细胞在所有样品中均显示出强烈的HSP90细胞质表达，并且55％的患者还表现出并发的核免疫阳性。与未处理的对照细胞相比，用17AAG处理U266细胞和原代MM细胞可导致凋亡明显增加。分析与17-AAG孵育的MM细胞中的抗凋亡BCL2家族蛋白和akt，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，但是17AAG和硼替佐米治疗的组合显示出对U266细胞系的协同凋亡作用。这些数据表明，针对HSP90的靶向抑制可能被证明是开发MM患者未来治疗选择的有效且创新的策略。

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细胞慢性淋巴细胞性白血病（B-CLL）。本研究旨在比较氟达拉滨或alemtuzumab治疗后长期未维持的缓解/高原期的B-CLL患者的信号分子表达和T细胞的细胞因子产生与惰性/未经治疗的B-CLL患者和健康供体的长期比较。通过流式细胞术检测TCR-CD3zeta链，p56lck，p59fyn，ZAP-70，PI3-激酶和干扰素（IFN）-γ/白介素（IL）-4在CD4和CD8 T细胞中产生的频率和强度。通过用纯化的蛋白质衍生物（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的表达明显高于健康供体。与健康供体相比，已治疗患者中大多数信号分子的强度相对未受影响，但低于未治疗的惰性患者。但是，表达每种信号分子的T细胞总数在患者中减少了，在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，对PHA而非TPD的T细胞反应降低了。结果表明，尽管在用氟达拉滨和阿仑单抗治疗后，长期而言，尽管信号分子发生了某些变化并且T细胞数量有所减少，但总体T细胞功能仍可以得到较好的保留。