BACKGROUND & AIMS: Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

背景与目标： Interleukin-1 α (IL-1 α) 在体外诱导多种良性细胞类型和一些但不是全部恶性细胞系中的细胞运动。这项研究表征了表达I型和II型IL-1受体的侵袭性人类黑素瘤细胞系的IL-1 α 诱导的运动。我们测试了单克隆抗体 (包括针对I型和II型IL-1受体的功能阻断moab) 对黑色素瘤细胞运动的影响，以确定哪种受体参与IL-1 α 诱导的黑色素瘤细胞运动的信号转导。IL-1 α 以剂量依赖的方式显著增加MM-RU黑素瘤细胞迁移，使用改进的Boyden室测定法，浓度低于显著抑制细胞生长的浓度的10至100倍。计算机辅助延时图像分析表明，通过中和针对IL-1 α 的抗体，运动性以剂量依赖的方式受到抑制。针对I型或II型IL-1受体的功能阻断单克隆抗体显示出对细胞因子诱导的增强细胞迁移的显着抑制。当两种anti-IL-1受体抗体加在一起时，运动反应完全阻断到控制水平。总之，这些数据表明，IL-1 α 诱导的MM-RU黑素瘤细胞的运动是通过I型和II型IL-1受体介导的。通过中和IL-1 α 或阻断一种或两种IL-1受体而显着抑制运动，表明IL-1-induced信号在诱导黑色素瘤细胞迁移中的整合。

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： : 口服耐受性是粘膜免疫系统的重要特征，似乎可以通过钝化针对慢性存在于粘膜表面的免疫原的全身性IgG和IgM抗体的产生来预防免疫介导的疾病。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) 实验模型中的作用，IgA肾病是人类肾炎的重要形式。环磷酰胺和雌二醇用于抑制口服耐受性的表达，否则口服耐受性会在Ag的慢性口服表现后发展。连续14周饮用含有0.1% 牛丙种球蛋白 (BGG) 的BALB/c小鼠被随机分配到给予2 mg环磷酰胺i.p.，2 mg雌二醇的组。或者两种药物。对照组小鼠既未接受BGG也未接受药物。在三个单独的实验中，低百分比的经生理盐水处理的经口服免疫的小鼠具有显微镜下血尿 (0至20%)，与未免疫的对照 (0至20%) 一样。然而，在适当的时间给予雌二醇和/或环磷酰胺的小鼠中有58至83% 出现明显的血尿。如果在次优时间给予药物，只有25至56% 的小鼠出现血尿。药物处理的免疫小鼠的血清IgG和IgM抗BGG抗体也比对照组和盐水组多。免疫荧光显示，与盐水处理的免疫小鼠和正常未经处理的对照小鼠相比，药物处理的免疫小鼠中IgG，IgM和C3的肾小球沉积明显更多。IgG，IgM和C3的血尿和肾小球沉积物与血清IgG和IgM抗体平行。所有免疫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，通过促进全身IgG和IgM抗体产生而使口服耐受性减弱会导致慢性口服免疫小鼠的肾炎，而含有IgG和/或IgM的肾小球免疫复合物会促进IgAN的补体沉积和血尿。口腔 (或更一般的粘膜) 耐受性的类似缺陷可能在有症状的人IgAN的发生中起作用。

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。

BACKGROUND & AIMS: Modelling and calculations are presented as a first step towards mechanistic interpretation and prediction of radiation effects based on the spectrum of initial DNA damage produced by low energy electrons (100 eV-4.5 keV) that can be compared with experimental information. Relative yields of single and clustered strand breaks are presented in terms of complexity and source of damage, either by direct energy deposition or by reaction of OH radicals, and dependence on the activation probability of OH radicals and the amount of energy required to give a single strand break (ssb). Data show that the majority of interactions in DNA do not lead to damage in the form of strand breaks and when they do occur, they are most frequently simple ssb. However, for double-strand breaks (dsb), a high proportion (approximately 30%) are of more complex forms, even without considering additional complexity from base damage. The greater contribution is from direct interactions in the DNA but reactions of OH radicals add substantially to this, both in terms of the total number of breaks and in increasing the complexity within a cluster. It has been shown that the lengths of damaged segments of DNA from individual electron tracks tend to be short, indicating that consequent deletion length (simply by loss of a fragment between nearby dsb) would be short, very seldom exceeding a few tens of base pairs.

背景与目标： 建模和计算是基于低能电子 (100 eV-4.5 keV) 产生的初始DNA损伤谱的辐射效应的机械解释和预测的第一步，可以与实验信息进行比较。通过直接能量沉积或OH自由基的反应，以及对OH自由基的激活概率和产生所需能量的依赖，以复杂性和损伤来源表示单链断裂 (ssb)。数据表明，DNA中的大多数相互作用不会以链断裂的形式导致损伤，当它们发生时，它们最常见的是简单的ssb。然而，对于双链断裂 (dsb)，高比例 (约30%) 是更复杂的形式，甚至不考虑来自基础损伤的额外复杂性。更大的贡献来自DNA中的直接相互作用，但是OH自由基的反应在断裂总数和增加簇内的复杂性方面都大大增加了这一点。已经表明，来自单个电子轨道的DNA受损片段的长度往往很短，这表明随之而来的缺失长度 (仅通过附近dsb之间的片段丢失) 将很短，很少超过几十个碱基对。

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。

BACKGROUND & AIMS: Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.

背景与目标： 左旋多巴引起的精神病会使帕金森氏病 (PD) 的治疗复杂化。在这份回顾性，不受控制的报告中，我们描述了我们用氯氮平治疗PD相关精神病的经验，强调了那些治疗时间超过1年的患者。27例患者接受了治疗，其中14例超过1年。使用临床总体印象和总体精神病评分，大多数患者在1个月内从基线显示出快速改善。五名患者因副作用而停药，但只有两名患者在治疗6个月后报告副作用。氯氮平似乎可有效治疗PD相关的精神病性症状，同时不干扰运动功能。

BACKGROUND & AIMS: :Sentinel lymph nodes (SLNs), being the first nodes to receive lymph from a primary tumour and the preferential site of initial tumour metastases, are intensively exposed to the bioactive products of tumour cells and other associated cells. This makes them ideal for studies of the factors that determine selective tissue susceptibility to metastases. We postulate that tumour-induced immune modulation of SLNs facilitates lymph-node metastases by inhibiting the generation of tumour-specific cytotoxic T cells that are active against tumour cells of primary and metastatic melanomas. Immune modulation of the lymph nodes can be reversed by granulocyte/macrophage colony-stimulating factor (GM-CSF), a finding that has implications for the future therapy of lymph-node metastases.

背景与目标： 前哨淋巴结 (sln) 是第一个从原发肿瘤接受淋巴结的淋巴结，也是最初肿瘤转移的优先部位，被大量暴露于肿瘤细胞和其他相关细胞的生物活性产物。这使得它们非常适合研究确定选择性组织对转移的敏感性的因素。我们假设，肿瘤诱导的sln的免疫调节通过抑制对原发性和转移性黑色素瘤的肿瘤细胞具有活性的肿瘤特异性细胞毒性T细胞的产生来促进淋巴结转移。可以通过粒细胞/巨噬细胞集落刺激因子 (gm-csf) 逆转淋巴结的免疫调节，这一发现对淋巴结转移的未来治疗有影响。

BACKGROUND & AIMS: BACKGROUND:A 79-year-old woman was referred for evaluation of her painful and swollen joints. She had a medical history of congestive heart failure, renal insufficiency and peptic ulcer disease. For the past 3 years she had experienced recurrent bouts of debilitating arthritis, lasting approximately 3-4 weeks at a time. The symptoms were most severe in the hands and knees, where the joints were warm, swollen and tender. During each flare-up, the patient was housebound and required therapeutic dosing of nonsteroidal anti-inflammatory drugs and codeine to control joint pain. INVESTIGATIONS:Physical examination, fine-detailed radiographs of the hands, standing radiographs of the knees, arthrocentesis including cell count and gram stain, compensated polarized light microscopy, alizarin-red staining, X-ray diffraction, scanning and transmission electron microscopy with energy dispersive spectrometry, electron microprobe analysis with energy dispersive spectrometry, Fourier transform infrared spectroscopy, and atomic force microscopy. DIAGNOSIS:Carbonated-substituted apatite arthropathy. MANAGEMENT:Both knees were aspirated and large volumes of a straw-colored synovial fluid was removed. The knees were injected with corticosteroid, resulting in excellent symptomatic response.

背景与目标：

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。

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。

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：

BACKGROUND & AIMS: :The signaling pathways mediating lysophosphatidic acid (LPA)-stimulated PKD(2) activation and the potential contribution of PKD(2) in regulating LPA-induced interleukin 8 (IL-8) secretion in nontransformed, human colonic epithelial NCM460 cells were examined. Treatment of serum-deprived NCM460 cells with LPA led to a rapid and striking activation of PKD(2), as measured by in vitro kinase assay and phosphorylation at the activation loop (Ser706/710) and autophosphorylation site (Ser876). PKD(2) activation induced by LPA was abrogated by preincubation with selective PKC inhibitors GF-I and Ro-31-8220 in a dose-dependent manner. These inhibitors did not have any direct inhibitory effect on PKD(2) activity. LPA induced a striking increase in IL-8 production and stimulated NF-kappaB activation, as measured by NF-kappaB-DNA binding, NF-kappaB-driven luciferase reporter activity, and IkappaBalpha phosphorylation. PKD(2) gene silencing utilizing small interfering RNAs targeting distinct PKD(2) sequences dramatically reduced LPA-stimulated NF-kappaB promoter activity and IL-8 production. PKD(2) activation is a novel early event in the biological action of LPA and mediates LPA-stimulated IL-8 secretion in NCM460 cells through a NF-kappaB-dependent pathway. Our results demonstrate, for the first time, the involvement of a member of the PKD family in the production of IL-8, a potent proinflammatory chemokine, by epithelial cells.

背景与目标： : 检测了介导溶血磷脂酸 (LPA) 刺激的PKD(2) 激活的信号通路，以及PKD(2) 在调节LPA诱导的白介素8 (IL-8) 分泌中的潜在作用。未转化的人结肠上皮NCM460细胞。用LPA处理血清剥夺的NCM460细胞导致PKD(2) 的快速和惊人的激活，如通过体外激酶测定和激活环 (Ser706/710) 和自磷酸化位点 (Ser876) 测量的。通过与选择性PKC抑制剂gf-i预孵育消除LPA诱导的PKD(2) 激活，并以剂量依赖性方式Ro-31-8220。这些抑制剂对PKD(2) 活性没有任何直接抑制作用。通过NF-κ b-DNA结合，NF-κ b驱动的荧光素酶报告活性和ikappaba磷酸化来测量，LPA诱导了IL-8产生的显着增加并刺激了NF-κ b活化。利用靶向不同PKD(2) 序列的小干扰rna沉默PKD(2) 基因显著降低LPA刺激的NF-κ b启动子活性和IL-8产生。PKD(2) 激活是LPA生物学作用中的一个新的早期事件，并通过NF-κ b依赖性途径介导NCM460细胞中LPA刺激的IL-8分泌。我们的结果首次证明了PKD家族成员参与了上皮细胞产生IL-8 (一种有效的促炎趋化因子)。

BACKGROUND & AIMS: :The gram-negative bacterium Bartonella henselae is capable of causing angiogenic lesions as a result of infection. Previously, it has been shown that B. henselae infection can result in production of the chemokine interleukin-8 (IL-8). In this study, we demonstrated that monocytes, endothelial cells, and hepatocytes produce IL-8 in response to B. henselae infection. We also investigated the role of IL-8 in B. henselae-induced endothelial cell proliferation and capillary tube formation. Both in vitro angiogenesis assays were IL-8 dependent. B. henselae-mediated inhibition of apoptosis, as indicated by gene expression of Bax and Bcl-2, was also shown to be IL-8 dependent in endothelial cells. Furthermore, infection of endothelial cells with B. henselae stimulated upregulation of the IL-8 chemokine receptor CXCR2. Infection of human endothelial cells by B. henselae resulting in IL-8 production likely plays a central role in the ability of this organism to cause angiogenesis during infection.

背景与目标： : 革兰氏阴性细菌Bartonella henselae能够由于感染而引起血管生成病变。以前，已经显示出B. henselae感染可导致趋化因子interleukin-8 (IL-8) 的产生。在这项研究中，我们证明了单核细胞，内皮细胞和肝细胞对B. henselae感染产生IL-8。我们还研究了IL-8在B. henselae诱导的内皮细胞增殖和毛细管形成中的作用。两种体外血管生成测定都是IL-8依赖性的。B. henselae介导的凋亡抑制，如Bax和Bcl-2的基因表达所表明的，也显示在内皮细胞中IL-8依赖性。此外，B. henselae感染内皮细胞会刺激IL-8趋化因子受体cxcr2的上调。B. henselae感染人内皮细胞导致IL-8产生可能在该生物体在感染期间引起血管生成的能力中起核心作用。

BACKGROUND & AIMS: :Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.

背景与目标： : 交感神经的维持性疼痛可以通过交感神经传出和传入伤害性纤维之间的触感相互作用来介导，也可以通过儿茶酚胺诱导的伤害性神经末梢的激活来介导。我们在此报告了一名患有交感持续疼痛的患者的C伤害感受器的单纤维记录，其中交感神经阻滞反复消除了双腿的持续疼痛。我们根据八种C纤维的机械响应性和与活动有关的传导速度减慢 (在0.125Hz下20个脉冲的0.5/-1.1与7.1/-2.0 ms的潜伏期增加)，将它们分类为机械敏感的伤害感受器。强烈的内源性交感神经爆发后，两根C纤维被激活，延迟数秒; 在将去甲肾上腺素 (10 microl，0.05%) 注射到其神经支配区域后，它们也被兴奋约3分钟。在这两种纤维中，记录了通过注射低pH溶液 (磷酸盐缓冲液，pH 6.0，10μl) 而延长的活化以及前列腺素E2注射后它们的热响应的敏化，证明了它们的传入性质。此外，对于机械不敏感的伤害感受器，它们的活性依赖性减慢是典型的。我们得出的结论是，内源性释放的儿茶酚胺可以激活敏感的机械不敏感伤害感受器，从而可能导致交感疼痛。没有发现交感传出和伤害性传入纤维之间的触觉相互作用的证据。

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。