BACKGROUND & AIMS: :A new inhibitor of human immunodeficiency virus (HIV) has been isolated and purified to homogeneity from the seeds and fruits of the Momordica charantia. This compound, MAP 30 (Momordica Anti-HIV Protein), is a basic protein of about 30 kDa. It exhibits dose-dependent inhibition of cell-free HIV-1 infection and replication as measured by: (i) quantitative focal syncytium formation on CEM-ss monolayers; (ii) viral core protein p24 expression; and (iii) viral-associated reverse transcriptase (RT) activity in HIV-1 infected H9 cells. The doses required for 50% inhibition (ID50) in these assays were 0.83, 0.22 and 0.33 nM, respectively. No cytotoxic or cytostatic effects were found under the assay conditions. These data suggest that MAP 30 may be a useful therapeutic agent in the treatment of HIV-1 infections. The sequence of the N-terminal 44 amino acids of MAP 30 has been determined.

背景与目标： : 已从苦瓜的种子和果实中分离并纯化出一种新的人类免疫缺陷病毒 (HIV) 抑制剂，使之同质。该化合物MAP 30 (苦味子抗HIV蛋白) 是约30 kDa的碱性蛋白。它表现出对无细胞HIV-1感染和复制的剂量依赖性抑制，通过以下方式测量 :( i) cem-ss单层上的定量局灶性合胞体形成; (ii) 病毒核心蛋白p24表达; 和 (iii) HIV-1感染的H9细胞中的病毒相关逆转录酶 (RT) 活性。在这些测定中50% 抑制所需的剂量 (ID50) 分别为0.83、0.22和0.33 nM。在测定条件下未发现细胞毒性或细胞抑制作用。这些数据表明，MAP 5月30日是治疗HIV-1感染的有用治疗剂。已确定MAP 30的N端44个氨基酸的序列。

BACKGROUND & AIMS: STUDY OBJECTIVE:To examine the prevalence, symptomatology, risk factors, and other infections associated with urogenital chlamydial infection in pregnant teenagers. DESIGN:Retrospective case-control study by medical record review. SETTING:Prenatal care clinic for adolescents at University of Tennessee Medical Center, Knoxville, Tennessee. PARTICIPANTS:Pregnant adolescents younger than 19 years of age who were diagnosed with chlamydial infection on the first prenatal visit from 1988 to 1994 were studied. Pregnant adolescents of similar age and socioeconomic background who came in the same day for the first prenatal visit, but were not infected, made up the control group. INTERVENTION:Routine prenatal questionnaires regarding personal and medical histories, and routine prenatal screening, including pelvic examination with Papanicolaou (PAP) smear and laboratory investigations for common genital infections and sexual transmitted disease (STDs), were obtained. MAIN OUTCOME MEASURES:Analyzed the prevalence of chlamydial infection and compared the infected group to the control group with regard to race, behavioral factors, symptoms, prenatal screening results, other concurrent genital infections, and histories of STDs. RESULTS:Of a total population of 596 pregnant teenagers, 67 (11.24%) were infected with Chlamydia trachomatis. In multivariate analysis, black race (odds ratio [OR] = 4.01; 95% confidence interval [CI] = 1.74-9.23; p = 0.001) and greater gestational age at first prenatal visit (OR = 1.11; 95% CI = 1.04-1.18; p = 0.001) were independently associated with chlamydial infection. Age, marital status, number of pregnancies, smoking, alcohol abuse, drug abuse, age at first intercourse, and multiple sex partners were not associated with the infection. Likewise, the symptom of vaginal discharge (a complaint of > 70% in each group), other genital co-infections (found > 50% in each group, mainly candidiasis and bacterial vaginosis), abnormal PAP smears (found > 60% in each group) and histories of STDs or previous chlamydial infection were not significantly different between case and control groups. Human papillomavirus infection, trichomonal infection, and dysplasia or atypia were found more often in patients infected with chlamydia, but were not statistically significant. CONCLUSION:Pregnant adolescents in east Tennessee were at risk for chlamydial infection as well as for other genital infections and abnormal PAP smears. Routine prenatal chlamydial screening is warranted because of a lack of specific symptoms.

背景与目标：

BACKGROUND & AIMS: :Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established. :A retrospective review was conducted of the medical records of 510 HIV-1-positive adult patients who had attended the Queen Elizabeth Hospital (QEH) to determine whether any had been admitted for an illness compatible with a diagnosis of primary HIV-1 infection. A serum bank, created from patients who had been admitted with acute febrile illnesses and investigated for leptospirosis, provided serological evidence for primary HIV-1 infection in 10 patients. Serological testing of the serum samples confirmed primary HIV-1 infection in nine patients and was suggestive in the tenth. The clinical features of the 10 patients fit the earlier descriptions of primary HIV-1 infection, but differed from the leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. These findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.

背景与目标：

BACKGROUND & AIMS: :Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both uninfected and HIV-infected cells. At therapeutic concentrations, ddCTP inhibits HIV replication by inhibiting the enzyme reverse transcriptase and terminating elongation of the proviral DNA chain. The results of 3 large pivotal trials comparing zidovudine monotherapy with combination therapy have now clearly established that zalcitabine plus zidovudine combination with an improvement in viral load and CD4+ cell count compared with zidovudine monotherapy. More recently, clinical end-point and surrogate marker data have established the efficacy of zalcitabine in combination with the protease inhibitor saquinavir in zidovudine-experienced patients. Other studies have demonstrated the utility of zalcitabine in combination with ritonavir and the nucleoside analogue lamivudine. Importantly, early use of zalcitabine in the treatment sequence does not appear to limit the therapeutic efficacy of subsequent therapy with other nucleoside analogues such as lamivudine. Peripheral neuropathy is the most frequent dose-limiting adverse effect associated with zalcitabine therapy and is generally reversible on discontinuation of treatment. Stomatitis and mouth ulcers may occur frequently with zalcitabine therapy but tend to resolve with continuing treatment. Haematological toxicity, which is a common adverse effect associated with zidovudine, is reported infrequently with zalcitabine. Overall, combination therapy with zalcitabine plus zidovudine or saquinavir has been shown to have a tolerability profile comparable to that of either agent alone, although treatment with zidovudine plus zalcitabine was associated with a significant increase in the incidence of haematological toxicity compared with zidovudine monotherapy in one study. Therefore, current data suggest that zalcitabine is a useful antiretroviral agent for inclusion as a component of initial double combination therapy with zidovudine or as part of triple combination therapy including zidovudine plus a protease inhibitor in the management of patients with HIV infection.

背景与目标： : 扎西他滨是一种双脱氧核苷抗逆转录病毒药物，在未感染和HIV感染的细胞中被磷酸化为活性代谢物2 '，3'-二脱氧胞苷5 '-三磷酸 (ddCTP)。在治疗浓度下，ddCTP通过抑制反转录酶和终止前病毒DNA链的延伸来抑制HIV复制。比较齐多夫定单药治疗与联合治疗的3项大型关键试验的结果现已清楚地确定，与齐多夫定单药治疗相比，扎西他滨加齐多夫定联合治疗的病毒载量和CD4细胞计数有所改善。最近，临床终点和替代标记数据已经确定了扎西他滨与蛋白酶抑制剂沙奎那韦联合使用齐多夫定经验的患者的疗效。其他研究表明扎西他滨与利托那韦和核苷类似物拉米夫定联合使用。重要的是，在治疗序列中早期使用扎西他滨似乎不会限制随后使用其他核苷类似物 (例如拉米夫定) 进行治疗的疗效。周围神经病变是与扎西他滨治疗相关的最常见的剂量限制性不良反应，并且在停止治疗后通常是可逆的。扎西他滨治疗可能经常发生口腔炎和口腔溃疡，但随着继续治疗而趋于缓解。扎西他滨很少报道血液学毒性，这是与齐多夫定相关的常见不良反应。总体而言，扎西他滨联合齐多夫定或沙奎那韦的联合治疗已被证明具有与单独使用任何一种药物相当的耐受性特征，尽管在一项研究中，与齐多夫定单药治疗相比，齐多夫定联合扎西他滨治疗与血液学毒性发生率显着增加有关。因此，目前的数据表明，扎西他滨是一种有用的抗逆转录病毒药物，可作为齐多夫定的初始双重联合疗法的一部分或作为齐多夫定加蛋白酶抑制剂的三重联合疗法的一部分纳入HIV感染患者。

BACKGROUND & AIMS: :Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.

背景与目标： : 人类免疫缺陷病毒 (HIV) 通过CD4与病毒包膜糖蛋白gp120之间的相互作用与细胞结合。先前的研究已将gp120的高亲和力结合位点定位于CD4的第一个结构域，与该区域反应性的单克隆抗体 (mab) 与gp120的结合竞争，从而阻止病毒的感染性和合胞体的形成。尽管对gp120与CD4的结合有详细的了解，但对导致膜融合和病毒进入的后续事件知之甚少。我们描述了两种与CD4的第三结构域反应的新mab，它们抑制了对HIV感染性和细胞融合至关重要的病毒结合之后的步骤。重组gp120或病毒与CD4的结合不受这些抗体的抑制，而许多HIV分离株的感染和合胞体形成被阻断。这些发现表明，除了病毒结合外，CD4可能在膜融合中起积极作用。

BACKGROUND & AIMS: :Burkholderia pseudomallei is a facultative intracellular pathogen and the causative agent of melioidosis, a spectrum of potentially fatal diseases endemic in Northern Australia and South-East Asia. We demonstrate that B. pseudomallei rapidly modifies infected macrophage-like cells in a manner analagous to osteoclastogenesis. These alterations include multinucleation and the expression by infected cells of mRNA for factors required for osteoclastogenesis: the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 gamma (MIP-1gamma), 'regulated on activation normal T cell expressed and secreted' (RANTES) and the transcription factor 'nuclear factor of activated T-cells cytoplasmic 1' (NFATc1). An increase in expression of these factors was also observed after infection with Burkholderia thailandensis. Expression of genes for the osteoclast markers calcitonin receptor (CTR), cathepsin K (CTSK) and tartrate-resistant acid phosphatase (TRAP) was also increased by B. pseudomallei-infected, but not by B. thailandensis-infected cells. The expression by B. pseudomallei-infected cells of these chemokine and osteoclast marker genes was remarkably similar to cells treated with RANKL, a stimulator of osteoclastogenesis. Analysis of dentine resorption by B. pseudomallei-induced osteoclast-like cells revealed that demineralization may occur but that authentic excavation does not take place under the tested conditions. Furthermore, we identified and characterized lfpA (for lactonase family protein A) in B. pseudomallei, which shares significant sequence similarity with the eukaryotic protein 'regucalcin', also known as 'senescence marker protein-30' (SMP-30). LfpA orthologues are widespread in prokaryotes and are well conserved, but are phylogenetically distinct from eukaryotic regucalcin orthologues. We demonstrate that lfpA mRNA expression is dramatically increased in association with macrophage-like cells. Mutation of lfpA significantly reduced expression of the tested host genes, relative to the response to wild-type B. pseudomallei. We also show that lfpA is required for optimal virulence in vivo.

背景与目标： : pseudomalei伯克霍尔德菌是一种兼性细胞内病原体，也是类鼻疽病的病原体，类鼻疽是澳大利亚北部和东南亚流行的一系列潜在致命疾病。我们证明假单胞菌以类似于破骨细胞发生的方式快速修饰感染的巨噬细胞样细胞。这些改变包括破骨细胞形成所需的因子的多核和感染细胞的mRNA表达: 趋化因子单核细胞趋化蛋白1 (MCP-1)，巨噬细胞炎性蛋白1 γ (MIP-1gamma)，“调节活化正常T细胞表达和分泌” (RANTES) 和转录因子 “活化T细胞胞质核因子1” (NFATc1)。感染泰国伯克霍尔德菌后，还观察到这些因子的表达增加。破骨细胞标记物降钙素受体 (CTR)，组织蛋白酶K (CTSK) 和耐酒石酸酸性磷酸酶 (TRAP) 的基因表达也被假假性芽孢杆菌感染的细胞增加，但未被泰国芽孢杆菌感染的细胞增加。这些趋化因子和破骨细胞标记基因的假假单胞菌感染细胞的表达与用破骨细胞生成刺激物RANKL处理的细胞非常相似。假单胞菌诱导的破骨细胞样细胞对牙本质的吸收分析表明，可能会发生脱矿质，但在测试条件下不会发生真正的挖掘。此外，我们在假单胞菌中鉴定并鉴定了lfpA (用于内酯酶家族蛋白A)，该蛋白与真核蛋白 “regucalin” (也称为 “衰老标记蛋白-30” (SMP-30)) 具有显着的序列相似性。LfpA直系同源物在原核生物中广泛存在，并且保存良好，但在系统发育上与真核生物regucalcin直系同源物不同。我们证明lfpA mRNA表达与巨噬细胞样细胞相关显着增加。相对于对野生型B.Pseudomalei的反应，lfpA的突变显着降低了所测试宿主基因的表达。我们还表明，lfpA是体内最佳毒力所必需的。

BACKGROUND & AIMS: Environmental pollution has become a major concern for the future of life on our planet; medical care, especially in hospitals, contributes significantly to this pollution. The increasing usage of highly-developed medical devices, drugs and disposable products are a drain on natural resources as well as financial ones. In this situation, it is a major task for hospital epidemiologists to maintain high standards of hygiene while reducing environmental pollution, reducing consumption of limited natural resources, and minimizing costs. The reduction of hospital waste, the control of polluting and toxic emissions, the avoidance of unnecessary disinfection procedures and disposables, the implementation of energy and water saving technologies are practicable measures in hospital ecology. To realize a sustainable development within hospitals, it is necessary that the need to maintain a balance between effective infection control and a good ecological environment is recognized and supported by health-care workers and the hospital management.

背景与目标： 环境污染已成为地球生命未来的主要问题; 医疗保健，尤其是医院的医疗保健，对这种污染有很大影响。高度发达的医疗设备，药品和一次性产品的使用日益增加，既消耗了自然资源，也消耗了金融资源。在这种情况下，医院流行病学家的主要任务是在减少环境污染的同时保持高标准的卫生，减少对有限自然资源的消耗并最大程度地降低成本。减少医院废物，控制污染和有毒排放物，避免不必要的消毒程序和一次性用品，实施节能节水技术是医院生态中的可行措施。为了实现医院内部的可持续发展，有必要在有效的感染控制和良好的生态环境之间保持平衡的需要得到医护人员和医院管理层的认可和支持。

BACKGROUND & AIMS: :IL-7 signals are crucial for the survival of naive and memory T cells, and the IL-7R is expressed on the surface of these cells. Following viral infection, the IL-7R is expressed on only a subset of effector CD8 T cells, and has been demonstrated to be important for the survival of these memory precursors. IL-7 message levels remain relatively constant during the T cell response to lymphocytic choriomeningitis virus, but a short-lived burst of GM-CSF is observed soon after infection. Retroviral expression of a chimeric GM-CSF/IL-7R, in which binding of GM-CSF by T cells leads to IL-7 signaling, allows for the delivery of an IL-7 signal in all effector T cells expressing the receptor. In mice infected with lymphocytic choriomeningitis virus, CD8 and CD4 T cells transduced with this chimeric receptor underwent an enhanced proliferative response compared with untransduced populations in the same host. Similarly, TCR transgenic CD8 cells expressing the chimeric receptor produced higher effector numbers during the peak of the T cell response to infection. Surprisingly, the enhanced proliferation did not lead to higher memory numbers, as the subsequent contraction phase was more pronounced in the transduced cell populations. These findings demonstrate that artificial IL-7 signaling during an infection leads to significantly increased Ag-specific effector T cell numbers, but does not result in increased numbers of memory progeny. The extent of contraction may be dictated by intrinsic factors related to the number of prior cell divisions.

背景与目标： : IL-7信号对于幼稚和记忆T细胞的存活至关重要，并且IL-7R在这些细胞的表面表达。病毒感染后，该IL-7R仅在效应cd8t细胞的子集上表达，并且已被证明对这些记忆前体的存活很重要。在T细胞对淋巴细胞性脉络丛脑膜炎病毒的反应期间，IL-7信息水平保持相对恒定，但是在感染后不久就观察到gm-csf的短暂爆发。嵌合gm-csf/IL-7R的逆转录病毒表达允许在表达该受体的所有效应T细胞中递送IL-7信号，其中gm-csf被T细胞结合导致IL-7信号。在感染了淋巴细胞性脉络丛脑膜炎病毒的小鼠中，与同一宿主中未转导的人群相比，用该嵌合受体转导的CD8和CD4 T细胞的增殖反应增强。同样，表达嵌合受体的TCR转基因CD8细胞在T细胞对感染的反应高峰期间产生更高的效应子数。令人惊讶的是，增强的增殖并未导致更高的记忆数，因为随后的收缩阶段在转导的细胞群体中更为明显。这些发现表明，感染期间的人工IL-7信号传导导致Ag特异性效应T细胞数量显着增加，但不会导致记忆后代数量增加。收缩的程度可能取决于与先前细胞分裂数量相关的内在因素。

BACKGROUND & AIMS: We describe a new principle for assessment of the activity of proteolytic enzymes of all classes and show the application of this principle for the quantitative assay of bacterial collagenase and human matrix metalloproteinases (MMPs). Central to this new principle is the presence of a proenzyme that can be activated into an active enzyme by a single proteolytic event. The regular activation sequence in the proenzyme is replaced using protein engineering by an artificial sequence recognized by the proteinase to be determined. The latter can act as an activator for the newly engineered proenzyme. In the present paper a simple colorimetric assay for the determination for MMPs is described based on this principle. With the aid of protein engineering, a modified pro-urokinase has been prepared in which the activation sequence normally recognized by plasmin (Pro-Arg-Phe-Lys upward arrowIle-Ile-Gly-Gly) has been replaced by a sequence expected to be recognized and hydrolysed by many MMPs (Arg-Pro-Leu-Gly upward arrowIle-Ile-Gly-Gly). The active urokinase resulting from activation of the modified pro-urokinase by a MMP could be measured either directly, using a specific chromogenic peptide substrate for urokinase, or indirectly via urokinase-catalysed plasminogen activation. The response of the assay to equal molar quantities of active MMPs decreases in the order MMP-2>MMP-9>MMP-1>MMP-3>MMP-7. The detection limit for MMP-9 was below 15 pM, corresponding to 3. 75x10(-15) mol per assay. Using the assay, increased MMP activity was detected in synovial tissue extracts from rheumatoid arthritis patients compared with those from osteoarthritis patients, and in stomach tumour extracts as compared with normal stomach tissue extracts.

背景与目标： 我们描述了一种评估所有类别蛋白水解酶活性的新原理，并展示了该原理在细菌胶原酶和人类基质金属蛋白酶 (MMPs) 定量测定中的应用。这一新原理的核心是存在一种原酶，该原酶可以通过一次蛋白水解事件被激活为活性酶。使用蛋白质工程技术将原酶中的常规激活序列替换为待确定的蛋白酶识别的人工序列。后者可以作为新改造的原酶的激活剂。在本文中，基于此原理描述了一种用于确定MMPs的简单比色测定法。借助蛋白质工程，已经制备了一种改良的尿激酶原，其中通常由纤溶酶识别的激活序列 (pro-Arg-Phe-Lys向上arrowIle-Ile-Gly) 已被预期被许多MMPs识别和水解的序列所取代 (Arg-Pro-Leu-Gly向上arrowIle-ile-Gly)。通过MMP激活修饰的尿激酶原而产生的活性尿激酶可以直接，使用尿激酶的特定显色肽底物进行测量，也可以通过尿激酶催化的纤溶酶原活化间接测量。测定对相等摩尔量的活性mmp的响应以MMP-2>MMP-9>MMP-1>MMP-3>MMP-7的顺序降低。MMP-9的检测限低于15μm，对应于3。每项测定75x10(-15) 摩尔。使用该测定法，类风湿关节炎患者的滑膜组织提取物与骨关节炎患者的滑膜组织提取物相比，以及与正常胃组织提取物相比，胃肿瘤提取物中的MMP活性增加。

BACKGROUND & AIMS: :Immunocompromise after a major injury is presumed to be a predisposing factor for sepsis. Mice subjected to sublethal cecal ligation and puncture (CLP) and challenged 5 days later with Pseudomonas aeruginosa had more bacterial growth in lung tissue, lower serum interferon gamma (IFN-gamma) and interleukin (IL) 12,and higher serum IL-10 when compared with sham CLP mice challenged with Pseudomonas. To test the functional significance of these alterations in cytokine production in the immune response to bacteria, we administered IFN-gamma and anti-IL-10 to post-CLP mice before the Pseudomonas challenge. Administration of IFN-gamma and anti-IL-10 did not improve bacterial clearance or mortality in post-CLP mice. In further studies, we administered IFN-gamma to IL-10 knockout mice before a challenge with P. aeruginosa. Our results showed no significant differences in bacterial clearance or mortality in IL-10 knockout mice with or without IFN-gamma treatment compared with wild-type controls. Finally, because most mortality occurred within 2 to 3 days of the Pseudomonas challenge in the aforementioned studies and was likely associated with a marked proinflammatory response, we investigated the effect of IFN-gamma and anti-IL-10 on clearance of Pseudomonas in C3H/HeJ mice, which do not mount an exaggerated proinflammatory response to endotoxin or Gram-negative bacteria. Neither clearance of the Pseudomonas bacteria nor mortality was improved in C3H/HeJ mice receiving anti-IL-10 and IFN-gamma. These results suggest that the suppressed IFN-gamma and IL-12 responses, in combination with an exaggerated IL-10 response to P. aeruginosa challenge after injury, do not correlate with bacterial clearance or survival.

背景与目标： : 重大损伤后的免疫损害被认为是败血症的诱发因素。与假单胞菌相比，接受亚致死性盲肠结扎和穿刺 (CLP) 并在5天后用铜绿假单胞菌攻击的小鼠肺组织中细菌生长更多，血清干扰素 γ (IFN-γ) 和白介素 (IL) 12降低，血清IL-10更高。为了测试这些细胞因子产生变化在对细菌的免疫反应中的功能意义，我们在假单胞菌攻击之前对CLP后小鼠施用IFN-γ 和anti-IL-10。施用IFN-γ 和anti-IL-10不会改善CLP后小鼠的细菌清除率或死亡率。在进一步的研究中，我们在用铜绿假单胞菌攻击之前对IL-10基因敲除小鼠施用IFN-γ。我们的结果表明，与野生型对照相比，有或没有IFN-γ 处理的IL-10基因敲除小鼠的细菌清除率或死亡率没有显着差异。最后，由于大多数死亡率发生在上述研究中假单胞菌攻击的2至3天内，并且可能与明显的促炎反应有关，因此我们研究了IFN-γ 和anti-IL-10对C3H/HeJ小鼠中假单胞菌清除的影响，它们不会对内毒素或革兰氏阴性细菌产生夸张的促炎反应。在接受anti-IL-10和IFN-γ 的C3H/HeJ小鼠中，假单胞菌的清除率和死亡率均未改善。这些结果表明，受抑制的IFN-γ 和IL-12反应，再加上损伤后对铜绿假单胞菌攻击的过度IL-10反应，与细菌清除或存活无关。

BACKGROUND & AIMS: :Thirty-three consecutive liver-transplant recipients were prospectively studied over a 37-mo period for evidence of cytomegalovirus infection. Sixteen (48%) episodes of cytomegalovirus infection were identified; 9 were primary infections and 7 were recurrent infections. Beginning with patient 8, gamma-globulin prophylaxis was routinely administered to most patients. Twelve potential risk factors for cytomegalovirus infection were evaluated and included pretransplant cytomegalovirus serological status of donor and recipient; recipient's age, sex, race, and liver disease; number and type of blood products transfused; type and intensity of immunosuppression; and occurrence of rejection. The Cox proportional hazards model identified positive donor cytomegalovirus serology as the single most important risk factor for subsequent development of cytomegalovirus infection, regardless of recipient cytomegalovirus serological status. In addition, use of gamma-globulin prophylaxis seemed to be protective against the occurrence of disseminated cytomegalovirus disease.

背景与目标： : 在37个月的时间内，对33位连续的肝移植受者进行了前瞻性研究，以寻找巨细胞病毒感染的证据。确定了16 (48%) 例巨细胞病毒感染; 9例为原发感染，7例为复发性感染。从患者8开始，大多数患者常规使用丙种球蛋白预防。评估了巨细胞病毒感染的十二个潜在危险因素，包括供体和受者的移植前巨细胞病毒血清学状态; 受者的年龄，性别，种族和肝脏疾病; 输血的血液制品的数量和类型; 免疫抑制的类型和强度; 和排斥的发生。Cox比例风险模型确定阳性供体巨细胞病毒血清学是随后发生巨细胞病毒感染的唯一最重要的危险因素，而与受体巨细胞病毒的血清学状况无关。此外，使用丙种球蛋白预防似乎可以预防弥漫性巨细胞病毒疾病的发生。

BACKGROUND & AIMS: :More than one-third of cellular proteomes traffic into and across membranes. Bacteria have invented several sophisticated secretion systems that guide various proteins to extracytoplasmic locations and in some cases inject them directly into hosts. Of these, the Sec system is ubiquitous, essential and by far the best understood. Secretory polypeptides are sorted from cytoplasmic ones initially due to characteristic signal peptides. Then they are targeted to the plasma membrane by chaperones/pilots. The translocase, a dynamic nanomachine, lies at the centre of this process and acts as a protein-conducting channel with a unique property; allowing both forward transfer of secretory proteins but also lateral release into the lipid bilayer with high fidelity and efficiency. This process, tightly orchestrated at the expense of energy, ensures fundamental cell processes such as membrane biogenesis, cell division, motility, nutrient uptake and environmental sensing. In the present review, we examine this fascinating process, summarizing current knowledge on the structure, function and mechanics of the Sec pathway.

背景与目标： : 超过3分之1的细胞蛋白质组进入和穿过膜。细菌已经发明了几种复杂的分泌系统，这些分泌系统将各种蛋白质引导到胞浆外位置，并在某些情况下将它们直接注入宿主。其中，Sec系统无处不在，必不可少，并且是迄今为止最好的理解。分泌多肽最初是由于特征性信号肽而从细胞质中分类的。然后，它们被伴侣/飞行员靶向质膜。转位酶是一种动态纳米机器，位于该过程的中心，并充当具有独特特性的蛋白质传导通道; 既可以向前转移分泌蛋白，又可以高保真度和效率地横向释放到脂质双层中。这一过程以能量为代价紧密协调，确保了基本的细胞过程，如膜生物发生、细胞分裂、运动、营养吸收和环境感知。在本综述中，我们研究了这一引人入胜的过程，总结了有关Sec途径的结构，功能和力学的最新知识。

BACKGROUND & AIMS: :The therapeutic potential of extracellular vesicles from eukaryotes has gained strong interest in recent years. However, research into the therapeutic application of their bacterial counterparts, known as bacterial membrane vesicles, is only just beginning to be appreciated. Membrane vesicles (MVs) from both Gram-positive and Gram-negative bacteria offer significant advantages in therapeutic development, including large-scale, cost effective production and ease of molecular manipulation to display foreign antigens. The nanoparticle size of MVs enables their dissemination through numerous tissue types, and their natural immunogenicity and self-adjuvanting capability can be harnessed to induce both cell-mediated and humoral immunity in vaccine design. Moreover, the ability to target MVs to specific tissues through the display of surface receptors raises their potential use as targeted MV-based anti-cancer therapy. This review discusses recent advances in MV research with particular emphasis on exciting new possibilities for the application of MVs in therapeutic design.

背景与目标： : 近年来，真核生物胞外囊泡的治疗潜力引起了人们的浓厚兴趣。然而，对细菌对应物 (称为细菌膜囊泡) 的治疗应用的研究才刚刚开始受到重视。革兰氏阳性和革兰氏阴性细菌的膜囊泡 (mv) 在治疗开发中具有显着优势，包括大规模，具有成本效益的生产以及易于显示外源抗原的分子操作。MVs的纳米颗粒大小使其能够通过多种组织类型传播，并且可以利用其天然免疫原性和自调节能力来诱导疫苗设计中的细胞介导和体液免疫。此外，通过表面受体的显示将MV靶向特定组织的能力提高了其作为靶向MV抗癌疗法的潜在用途。这篇综述讨论了MV研究的最新进展，特别强调了MV在治疗设计中应用的令人兴奋的新可能性。

BACKGROUND & AIMS: :We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option.

背景与目标： : 我们描述了在重症监护环境中用于严重二元毒素阳性艰难梭菌感染的粪便微生物移植 (FMT) 病例。该患者被送入三级医院的ICU，但传统的最大药理学管理失败。通过胃镜检查给予FMT辅助治疗可缓解艰难梭菌相关症状。尽管FMT用于复发性艰难梭菌感染的经验不断增加，但在严重疾病中发表的证据非常有限。在日益严重的艰难梭菌感染的情况下，辅助FMT可能被认为是一种有用的早期治疗选择。

BACKGROUND & AIMS: Objective:To estimate the cumulative incidence of persistent arthralgia at 6 months from acute Chikungunya virus (CHIKV) infection and to evaluate the association of clinical markers with the risk of long-term arthralgia. Methods:This multicenter retrospective cohort study was conducted in the Mexican state of Colima. A total of 136 individuals aged 15 years and older with serologically confirmed CHIKV infection were enrolled. Participants were interviewed at 6 months from the onset of symptoms, and self-reported persistent arthralgia (PA) was the main binary outcome. A self-report numeric rating scale (NRS) ranging from 0 to 10 was used to estimate the severity of articular pain. Results:The cumulative incidence of PA was 41.9%. Severe pain (NRS ≥ 7) presented in 36.8% of participants with PA. In multiple analysis, individuals aged 40 years and older (risk ratio (RR) = 1.60; 95% confidence interval (CI), 1.03-2.48) and those with articular pain at 3 months post-infection (RR = 3.95; 95% CI, 1.95-8.01) had a significantly increased risk of PA at 6 months from CHIKV infection. Conclusions:To the best of our knowledge, this is first report of a CHIKV-associated long-term outcome in Mexico, where the incidence of the infection has been high. This is also the first study in Latin America evaluating several factors associated with the risk of PA. Our findings may be useful in health care settings to stratify the risk of chronic arthralgia secondary to CHIKV infection and to identify patients who would benefit clinically from early medical intervention.

背景与目标：