BACKGROUND & AIMS: :Methicillin/oxacillin (Oxa) resistance in Staphylococcus aureus is primarily mediated by the acquired penicillin-binding protein (PBP2a) encoded by mecA. PBP2a acts together with native PBP2 to mediate oxacillin resistance by contributing complementary transpeptidase and transglycosylase activities, respectively. The VraS/VraR two-component regulatory system is inducible by cell-wall antimicrobials (beta-lactams, glycopeptides) and controls transcriptional induction of many cell-wall genes including pbp2 and itself. We investigated the role of VraS/VraR in the phenotypic expression of oxacillin resistance by inactivating vraS in community-acquired MRSA clinical isolates that lack functional genes encoding the mecA regulatory sequences mecI and mecR1. Inactivation of vraS abrogated oxacillin resistance, and complementation with the vraS operon restored the resistance phenotype. mecA transcription increased in the vraS mutants; however, PBP2a abundance was similar to that of the wild type. Although pbp2 transcription decreased in the vraS mutants, overexpression of the pbp2 operon did not restore resistance. These data demonstrate that although expressions of mecA and pbp2 are required for oxacillin resistance, they are not sufficient. Therefore, the vraS/vraR regulatory system plays a crucial role in allowing MRSA to respond to beta-lactams by regulation of a gene target other than the known effectors of methicillin resistance.

背景与目标： 金黄色葡萄球菌对甲氧西林/奥沙西林（Oxa）的耐药性主要由mecA编码的获得性青霉素结合蛋白（PBP2a）介导。 PBP2a与天然PBP2共同发挥作用，通过分别贡献互补的转肽酶和转糖基酶活性来介导奥沙西林抗性。 VraS / VraR两组分调节系统可通过细胞壁抗微生物剂（β-内酰胺，糖肽）诱导，并控制包括pbp2及其本身在内的许多细胞壁基因的转录诱导。我们通过灭活社区获得的MRSA临床分离株中的vraS而失活，研究了VraS / VraR在奥沙西林抗性表型表达中的作用，该分离株缺乏编码mecA调控序列mecI和mecR1的功能基因。 vraS的失活消除了奥沙西林的耐药性，与vraS操纵子的互补恢复了耐药性表型。在vraS突变体中，mecA转录增加；但是，PBP2a的丰度与野生型相似。尽管在vraS突变体中pbp2转录降低，但是pbp2操纵子的过表达不能恢复抗性。这些数据表明，尽管抗mecA和pbp2的表达是奥沙西林耐药性所必需的，但它们还不够。因此，vraS / vraR调节系统在允许MRSA通过调节除已知的甲氧西林抗性效应子以外的基因靶标而对β-内酰胺作出响应中起着至关重要的作用。

BACKGROUND & AIMS: :Rhizoxin is an antineoplastic drug that inhibits tubulin polymerization. In this study, we demonstrated that rhizoxin was approximately twice as active in vitro against a human small-cell lung cancer cell line with non-P-glycoprotein-mediated resistance to vindesine, H69/VDS, as against its parental line, H69. Tubulin polymerization in H69/VDS, demonstrated by Western blot analysis, was inhibited markedly by rhizoxin compared with that in H69, in a concentration-dependent manner. A drug-accumulation study showed that the intracellular rhizoxin level in H69/VDS was 15% lower than that in H69, whereas efflux from H69/VDS was enhanced slightly. These results indicate that enhanced inhibition of tubulin polymerization rather than increased intracellular drug concentration accounted for the higher sensitivity of H69/VDS to rhizoxin. In an experiment using mice with severe combined immunodeficiency and inoculated subcutaneously with H69/VDS, in vivo tumor growth was reduced markedly by three intermittent intraperitoneal doses of rhizoxin compared with that in mice inoculated with H69. Three weeks after the last rhizoxin dose, the relative treated/untreated tumor volumes were 0.29 for H69, but only 0.06 for H69/VDS, indicating that H69/VDS regrowth was minimal even after a 3-week treatment-free period. In conclusion, rhizoxin conquers vindesine resistance of a human small-cell lung cancer cell line in vitro and in vivo.

背景与目标： ：Rhizoxin是一种抑制微管蛋白聚合的抗肿瘤药。在这项研究中，我们证明了根霉毒素在体外对人小细胞肺癌细胞株的活性约为非亲本糖蛋白对长春地辛H69 / VDS的抗性（相对于其亲本株H69）的两倍。 Western blot分析表明，与H69相比，根瘤菌素显着抑制了H69 / VDS中的微管蛋白聚合，且呈浓度依赖性。一项药物蓄积研究表明，H69 / VDS中的细胞内根瘤菌素水平比H69低15％，而H69 / VDS的外排量则略有提高。这些结果表明，增强的对微管蛋白聚合的抑制而不是增加的细胞内药物浓度，说明了H69 / VDS对根瘤菌素的敏感性更高。在一项使用严重联合免疫缺陷小鼠并皮下接种H69 / VDS的小鼠进行的实验中，与接种H69的小鼠相比，腹膜内三剂间断性的根瘤菌素显着降低了体内肿瘤的生长。在最后一剂根瘤菌素给药后三周，H69的相对治疗/未治疗肿瘤体积为0.29，而H69 / VDS仅为0.06，这表明即使经过3周的无治疗期，H69 / VDS的再生长也很小。总之，根瘤菌素可在体外和体内克服人类小细胞肺癌细胞株的长春地辛耐药性。

BACKGROUND & AIMS: :Chondrogenesis occurs in vivo in a hypoxic environment, in which the hypoxia inducible factor 1, HIF-1, plays a regulatory role, possibly mediated through the transcription factor DEC1. We have analyzed the effect of hypoxia (1% oxygen) alone and in combination with insulin on the chondrogenic differentiation of the mouse embryonic stem cell line ATDC5. Hypoxic treatment alone induced early chondrogenesis as evidenced by enhanced expression of aggrecan and collagen II, whereas hypoxic incubation of insulin-treated cells delayed and suppressed insulin-mediated early chondrogenesis and almost completely blocked hypertrophic differentiation. Paradoxically, the transcriptional activation of DEC1 was invariably enhanced by the hypoxic exposure.

背景与目标： ：软骨形成发生在体内低氧环境中，在该环境中，缺氧诱导因子1（HIF-1）发挥调节作用，可能是通过转录因子DEC1介导的。我们已经分析了单独和与胰岛素联合使用低氧（1％氧气）对小鼠胚胎干细胞系ATDC5软骨分化的影响。单用低氧治疗可诱导早期软骨形成，聚集蛋白聚糖和胶原II的表达增强证明了这一点，而对胰岛素处理的细胞进行低氧培养可延迟并抑制胰岛素介导的早期软骨形成，并且几乎完全阻断了肥大细胞的分化。矛盾的是，低氧暴露总是增强了DEC1的转录激活。

BACKGROUND & AIMS: :Gliomas are highly lethal neoplasms that cannot be cured by currently available therapies. Temozolomide is a recently introduced alkylating agent that has yielded a significant benefit in the treatment of high-grade gliomas. However, either de novo or acquired chemoresistance occurs frequently and has been attributed to increased levels of O6-methylguanine-DNA methyltransferase or to the loss of mismatch repair capacity. However, very few gliomas overexpress O6-methylguanine-DNA methyltransferase or are mismatch repair-deficient, suggesting that other mechanisms may be involved in the resistance to temozolomide. The purpose of the present study was to generate temozolomide-resistant variants from a human glioma cell line (SNB-19) and to use large-scale genomic and transcriptional analyses to study the molecular basis of acquired temozolomide resistance. Two independently obtained temozolomide-resistant variants exhibited no cross-resistance to other alkylating agents [1,3-bis(2-chloroethyl)-1-nitrosourea and carboplatin] and shared genetic alterations, such as loss of a 2p region and loss of amplification of chromosome 4 and 16q regions. The karyotypic alterations were compatible with clonal selection of preexistent resistant cells in the parental SNB-19 cell line. Microarray analysis showed that 78 out of 17,000 genes were differentially expressed between parental cells and both temozolomide-resistant variants. None are implicated in known resistance mechanisms, such as DNA repair, whereas interestingly, several genes involved in differentiation were down-regulated. The data suggest that the acquisition of resistance to temozolomide in this model resulted from the selection of less differentiated preexistent resistant cells in the parental tumor.

背景与目标： ：胶质瘤是高度致死性的肿瘤，目前尚无法治愈。替莫唑胺是最近引入的烷基化剂，已在治疗高级神经胶质瘤中产生了显着的益处。然而，从头发生或获得性抗药性经常发生，并且归因于O6-甲基鸟嘌呤-DNA甲基转移酶水平的增加或错配修复能力的丧失。但是，极少的神经胶质瘤过表达O6-甲基鸟嘌呤-DNA甲基转移酶或错配修复缺陷，提示其他机制可能与对替莫唑胺的抗性有关。本研究的目的是从人类神经胶质瘤细胞系（SNB-19）产生抗替莫唑胺的变体，并使用大规模的基因组和转录分析来研究获得的替莫唑胺抗性的分子基础。两个独立获得的替莫唑胺抗性变体对其他烷基化剂[1,3-双（2-氯乙基）-1-亚硝基脲和卡铂]无交叉抗性，并且共有遗传变异，例如2p区域丢失和扩增丢失染色体4和16q区域。核型改变与亲本SNB-19细胞系中先前存在的抗性细胞的克隆选择相容。基因芯片分析显示，在17,000个基因中，有78个在亲代细胞和两种替莫唑胺耐药变体之间差异表达。没有人参与已知的抗性机制，例如DNA修复，而有趣的是，参与分化的几个基因被下调。数据表明，在该模型中获得对替莫唑胺的抗药性是由于在亲本肿瘤中选择了分化程度较低的抗药性细胞而引起的。

BACKGROUND & AIMS: :In the last few years, our knowledge of genetically determined causes of short stature has greatly increased by reports of challenging patients, who offered the opportunity to study genes that play a role in growth. Since the first paper that showed the etiology of Laron syndrome [Godowski PJ, et al: Proc Natl Acad Sci USA 1989;86:8083-8087], many mutations in the growth hormone (GH) receptor have been identified. Recently, new mutations or deletions have been found in several components of the GH-insulin-like growth factor-I (IGF-I) axis: a homozygous mutation of the GH1 gene, resulting in a bio-inactive GH; mutations in the STAT5b gene, which plays a major role in the GH signal transduction; a homozygous missense mutation in the IGF-I gene; heterozygous mutations in the IGF-I receptor gene and a homozygous deletion of the acid-labile subunit gene. In this mini review, we describe the clinical and biochemical features of these genetic defects. Genetic analysis has become essential in the diagnostic workup of a patient with short stature. However, regarding the time consuming nature of molecular analysis, it is important to carefully select the patient for specific genetic evaluation. To help in this selection process, we developed flowcharts, based on the recently described patients, that can be used as guidelines in the diagnostic process of patients with severe short stature of unknown origin.

背景与目标： ：在过去的几年中，由于对挑战性患者的报道，我们对遗传决定的矮小身高原因的了解大大增加了，这些患者为研究在生长中起作用的基因提供了机会。自从第一篇显示Laron综合征病因的论文[Godowski PJ等人：Proc Natl Acad Sci USA 1989; 86：8083-8087]以来，已经确定了生长激素（GH）受体的许多突变。最近，在GH-胰岛素样生长因子-I（IGF-I）轴的几个组成部分中发现了新的突变或缺失：GH1基因的纯合突变，导致了生物失活的GH； STAT5b基因的突变，在GH信号转导中起主要作用； IGF-I基因的纯合错义突变； IGF-1受体基因中的杂合突变和对酸不稳定的亚基基因的纯合缺失。在这个小型综述中，我们描述了这些遗传缺陷的临床和生化特征。遗传分析已成为身材矮小的患者的诊断检查中必不可少的。但是，考虑到分子分析的耗时性质，重要的是要仔细选择患者进行特定的基因评估。为了帮助选择过程，我们根据最近描述的患者制定了流程图，可以将其用作诊断患有严重身材矮小，来源不明的患者的诊断过程中的指导原则。

BACKGROUND & AIMS: CONTEXT:Concern has been raised about the safety of assisted reproduction techniques for the offspring. OBJECTIVES:The objective of the study was to investigate postnatal growth and growth factors in children born after intra-cytoplasmatic sperm injection (ICSI) and in vitro fertilization (IVF). DESIGN:The study had two cohorts: a population-based longitudinal infant cohort 0-36 months [236 ICSI, 173 IVF, 1530 naturally conceived (NC)], and a cross-sectional child cohort at 5 yr (68 ICSI, 67 IVF, 70 NC). INTERVENTION:Anthropometrical measurements were made at birth, 3, 18, 36 (infant cohort), and 60 months (child cohort), and blood samples were collected at 3 or 60 months. MAIN OUTCOME MEASURES:Serum IGF-I, IGFBP-3, height, weight, head and abdominal circumference, body mass index, and fat folds were the main outcome measures. RESULTS:Anthropometrical measurements showed no significant differences between ICSI and IVF children and controls in either cohort. However, singleton ICSI girls [3.4 (0.6) kg, P = 0.008] had a slightly lower birth weight than IVF [3.5 (0.5) kg] and NC girls [3.5 (0.5) kg]. Birth weights of singleton boys [3.6 (0.5) kg], twin boys [2.6 (0.6) kg], and twin girls [2.4 (0.5) kg] did not differ between types of conception. In the infant cohort in 3-month-old singletons, serum IGF-I was lower in ICSI [78 (26) ng/ml] than NC boys [94 (27) ng/ml, P < 0.001] and IVF [74 (34) ng/ml], compared with NC girls [93 (43) ng/ml, P = 0.011]. ICSI children were also smaller than their target height (sd score) at 3 yr of age [mean -0.91 (1.2)], compared with NC children [-0.61 (0.9), P = 0.033]. In the child cohort, target height attainment (sd score) and growth factors did not differ among the three groups. CONCLUSIONS:The overall growth pattern of ICSI and IVF children in both cohorts was normal. Our findings of subtle differences in target height attainment and serum IGF-I levels between infants born after assisted reproduction techniques and controls may not be clinically significant. However, these observations indicate that further systematic follow-up of growth and puberty in these children is needed.

背景与目标： 背景：人们对后代辅助生殖技术的安全性表示关注。
目的：本研究的目的是调查胞浆内精子注射（ICSI）和体外受精（IVF）后出生的儿童的出生后生长和生长因子。
设计：该研究有两个队列：基于人群的纵向婴儿队列0-36个月[236 ICSI，173 IVF，1530自然受孕（NC）]和5岁时的横断面儿童队列（68 ICSI，67 IVF ，70 NC）。
干预措施：分别在出生时，3、18、36（婴儿队列）和60个月（儿童队列）进行人体测量，并在3或60个月时采集血样。
主要观察指标：血清IGF-I，IGFBP-3，身高，体重，头围和腹围，体重指数和脂肪褶皱是主要的观察指标。
结果：人体测量结果显示，ICSI和IVF儿童与对照组之间均无显着差异。但是，单身ICSI女孩[3.4（0.6）千克，P = 0.008]的出生体重略低于IVF [3.5（0.5）千克]和NC女孩[3.5（0.5）千克]。单胎男孩[3.6（0.5）千克]，双胞胎男孩[2.6（0.6）千克]和双胞胎女孩[2.4（0.5）千克]的出生体重在不同的受孕类型之间没有差异。在3个月大的单胎婴儿队列中，ICSI的血清IGF-I低于NC男孩[94（27）ng / ml，P <0.001]和IVF [74（ 34）ng / ml]，而NC女生则为[93（43）ng / ml，P = 0.011]。与3岁儿童相比，ICSI儿童在3岁时也小于其目标身高（sd评分）[平均-0.91（1.2）]，而NC儿童则为[-0.61（0.9），P = 0.033]。在儿童队列中，三组之间的目标身高获得（sd得分）和生长因子没有差异。
结论：两组人群ICSI和IVF儿童的总体生长方式均正常。我们在辅助生殖技术和对照后出生的婴儿之间的目标身高获得和血清IGF-I水平细微差异的发现可能在临床上并不重要。但是，这些观察结果表明，需要对这些儿童的生长和青春期进行进一步的系统随访。

BACKGROUND & AIMS: :Reports on the efficacy of physical activity intervention trials usually only include discussion of the primary outcomes. However, assessing factors such as participant retention, adherence and compliance can assist in the accurate interpretation of the overall impact of a program in terms of reach and appeal. A quasi-randomised trial was carried out to assess and compare retention and adherence rates, and compliance with, a twice weekly resistance training program provided either individually at home or in a group format. Retirement villages (n=6) were assigned to either 'Have A Try' (HAT, home-based) or 'Come Have A Try' (CHAT, group-based); both programs included nine strength and two balance exercises. The program involved a 20-week Intervention Phase a 24-week Maintenance Phase and a 20-week On-going Maintenance Phase. One hundred and nineteen participants (mean age 80+/-6 years) were recruited (HAT=38, CHAT=81). There was no difference in retention rates at the end of the Intervention Phase, but significantly more HAT than CHAT participants had dropped out of the study (p<0.01) after the Maintenance Phase and the On-going Maintenance Phase. During the Intervention Phase, over half the HAT and CHAT participants completed > or =75% of the prescribed activity sessions, but adherence was significantly greater in CHAT than HAT during the Maintenance Phase (p<0.01). Participants in CHAT were significantly more compliant than HAT participants (p<0.05). Both home- and group-based formats were successful over the short-term, but, in retirement villages, the group program had better adherence and compliance in the longer-term.

背景与目标： ：有关体育锻炼干预试验功效的报告通常仅包括对主要结局的讨论。但是，评估参与者的保留，遵守和遵守等因素可以帮助准确地解释计划在影响力和吸引力方面的总体影响。进行了一项半随机试验，以评估和比较保留率和依从率，以及是否遵守每周两次的在家中或以小组形式提供的每周两次阻力训练计划。退休村（n = 6）被分配为“尝试一下”（HAT，基于家庭）或“来一下尝试”（CHAT，基于组）；这两个程序都包括九项力量和两项平衡练习。该计划包括20周的干预阶段，24周的维护阶段和20周的持续维护阶段。招募了119名参与者（平均年龄80 / -6岁）（HAT = 38，CHAT = 81）。在干预阶段结束时，保留率没有差异，但是在维护阶段和正在进行的维护阶段之后，HAT的退出人数比CHAT参与者退出研究的次数多（p <0.01）。在干预阶段，超过一半的HAT和CHAT参与者完成了规定活动的>或= 75％，但是在维持阶段，CHAT中的依从性明显高​​于HAT（p <0.01）。与CHAT参与者相比，CHAT参与者的依从性更高（p <0.05）。以家庭为基础和以团体为基础的形式在短期内都是成功的，但是在退休村，从长期来看，团体计划具有更好的遵守性和合规性。

BACKGROUND & AIMS: :The biological actions of the insulin-like growth factors, IGF-I and IGF-II, are mediated by the ligand-induced activation of the IGF-I receptor (IGF-IR), a transmembrane heterotetramer linked to the ras-raf-mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3 kinase (PI3K)-protein kinase B (PKB)/Akt signal transduction cascades. The Wilms' tumor suppressor gene (wt1) encodes a zinc finger transcription factor, WT1, which has been implicated in various cellular processes including proliferation, differentiation and apoptosis. In the present study we demonstrated that IGF-I modulates the WT1 gene expression in neurally derived PC12 cells in a dose- and time-dependent manner. This effect was mediated through both the MAPK and PI3-kinase signaling pathways, as shown by the ability of the specific inhibitors UO126 and LY294002 to abrogate IGF-I action. Moreover, using RT-PCR and transient transfection assays, we demonstrated that the IGF-I effect was associated with corresponding changes in WT1 mRNA levels and WT1 promoter activity. In addition, the results of the present study revealed that high WT1 levels were associated with the induction of apoptosis, whereas low WT1 levels were correlated with the inhibition of apoptosis, as demonstrated by poly ADP ribose polymerase (PARP) cleavage, Bax expression, Annexin V-FITC staining, and by the use of antisense oligonucleotides against WT1. In summary, our results show that the wt1 gene is a novel target for IGF-I action in neurally derived cells.

背景与目标： 胰岛素样生长因子IGF-I和IGF-II的生物学作用是由配体诱导的IGF-I受体（IGF-IR）活化而介导的，IGF-IR受体是与ras-raf-连接的跨膜异四聚体丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3激酶（PI3K）-蛋白激酶B（PKB）/ Akt信号转导级联反应。威尔姆斯的肿瘤抑制基因（wt1）编码锌指转录因子WT1，该因子已参与多种细胞过程，包括增殖，分化和凋亡。在本研究中，我们证明了IGF-1以剂量和时间依赖性的方式调节神经源性PC12细胞中WT1基因的表达。这种作用是通过MAPK和PI3激酶信号传导途径介导的，如特异性抑制剂UO126和LY294002消除IGF-I作用的能力所示。此外，使用RT-PCR和瞬时转染试验，我们证明了IGF-I的作用与WT1 mRNA水平和WT1启动子活性的相应变化有关。此外，本研究结果表明，高WT1水平与凋亡诱导相关，而低WT1水平与凋亡抑制相关，如聚ADP核糖聚合酶（PARP）裂解，Bax表达，膜联蛋白所证明的。 V-FITC染色，并使用针对WT1的反义寡核苷酸。总而言之，我们的结果表明wt1基因是神经衍生细胞中IGF-I作用的新靶标。

BACKGROUND & AIMS: :Insulin resistance affecting skeletal muscle metabolism is present in the prehypertensive state. The aim of our study was to test the hypothesis that blood pressure value is related to skeletal muscle composition, measured by (31)P magnetic resonance (MR) spectroscopy, and to insulin sensitivity in the offspring of hypertensive parents (OH) and healthy controls. Study groups consisted of 10 healthy young lean OH with normal glucose tolerance, confirmed with oral glucose tolerance test, and 13 controls matched for age, sex, and body mass index. Insulin action was estimated as glucose disposal (M), glucose metabolic clearance rate (MCR), and insulin sensitivity index (M/I) during a 10-hour hyperinsulinemic euglycemic clamp. The sum of immunoreactive insulin values from the oral glucose tolerance test was calculated. (31)P MR spectroscopy was performed on a whole-body MR scanner (Siemens Vision, Erlangen, Germany) operating at 1.5 T and equipped with actively shielded gradient coils. There were no differences in common metabolic and anthropometric parameters between OH and controls except for the blood pressure, which was in the range of normal to high-normal level in OH. Mean blood pressure was significantly higher in OH (95.73 +/- 4.39 vs 83.76 +/- 3.95 mm Hg; P < .001). Trend toward insulin resistance was registered in OH with significantly lower M/I (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg x kg(-1) x min(-1) x mIU(-1) x L(-1); P < .05). There were no significant differences in total serum magnesium (sMg) levels between OH and controls, although a positive correlation exists between sMg and insulin sensitivity expressed as M (r = 0.63, P < .01), MCR (r = 0.54, P < .01), and M/I (r = 0.51, P < .05). No differences in signal intensities of phosphocreatine (PCr), phosphomonoesters, phosphodiesters, inorganic phosphates (Pi), adenosine triphosphates (Patp and betaATP), and calculated concentrations of intracellular ionized magnesium (Mgi) and H(+) ions between the groups were detected. Systolic blood pressure correlates positively with PCr/Patp (r = 0.43, P < .05), Pi/Patp (r = 0.413, P < .05), and Pi/betaATP (r = 0.48, P < .05). Diastolic blood pressure correlates positively only with the ratio Pi/betaATP (r = 0.42, P < .05). The sum of immunoreactive insulin values correlates with PCr/betaATP (r = 0.53, P < .01) and with Pi/betaATP (r = 0.6, P < .01). In conclusion, increase in blood pressure and insulin resistance were confirmed in offspring of OH. Insulin sensitivity is related to sMg and the elevation of blood pressure is associated with the activation of energy metabolism in skeletal muscle. The relationship between muscle energetic characteristics and markers of insulin resistance suggests that the alteration of energy metabolism may be present in early stages of metabolic syndrome.

背景与目标： ：在高血压前状态下，会影响骨骼肌新陈代谢的胰岛素抵抗。我们研究的目的是检验以下假设：血压值与通过（31）P磁共振（MR）光谱法测量的骨骼肌成分以及高血压父母（OH）和健康对照的后代的胰岛素敏感性有关。研究组包括10名健康正常的年轻瘦肉OH，其葡萄糖耐量正常，经口服葡萄糖耐量试验确认，另有13个对照的年龄，性别和体重指数匹配。在10小时高胰岛素正常血糖钳制期间，胰岛素作用估计为葡萄糖处置（M），葡萄糖代谢清除率（MCR）和胰岛素敏感性指数（M / I）。计算来自口服葡萄糖耐量试验的免疫反应性胰岛素值的总和。 （31）P MR光谱是在全身MR扫描仪（Siemens Vision，Erlangen，德国）上以1.5 T操作并配备有源屏蔽梯度线圈进行的。 OH和对照组之间的共同代谢和人体测量学参数没有差异，除了血压处于OH正常水平到高正常水平的范围之内。 OH的平均血压显着升高（95.73 /-4.39与83.76 /-3.95 mm Hg； P <.001）。在OH中出现胰岛素抵抗的趋势，M / I显着降低（0.74 /-0.47对1.42 /-0.65 mg x kg（-1）x min（-1）x mIU（-1）x L（-1）; P <.05）。尽管sMg与胰岛素敏感性之间呈正相关，以M（r = 0.63，P <.01），MCR（r = 0.54，P < .01）和M / I（r = 0.51，P <.05）。在两组之间没有发现磷酸肌酸（PCr），磷酸单酯，磷酸二酯，无机磷酸盐（Pi），三磷酸腺苷（Patp和betaATP）的信号强度以及计算出的细胞内离子化镁（Mgi）和H（）浓度的差异。收缩压与PCr / Patp（r = 0.43，P <.05），Pi / Patp（r = 0.413，P <.05）和Pi / betaATP（r = 0.48，P <.05）正相关。舒张压仅与Pi / betaATP比率呈正相关（r = 0.42，P <.05）。免疫反应性胰岛素值的总和与PCr / betaATP（r = 0.53，P <.01）和Pi / betaATP（r = 0.6，P <.01）相关。总之，在OH的后代中证实了血压升高和胰岛素抵抗。胰岛素敏感性与sMg有关，血压升高与骨骼肌能量代谢的激活有关。肌肉能量特性与胰岛素抵抗标志物之间的关系表明，能量代谢的改变可能在代谢综合征的早期出现。

BACKGROUND & AIMS: :To our knowledge, the relationship between gallbladder volume and cystic duct function has not been studied. We hypothesized that changes in gallbladder volume would influence cystic duct resistance. The effect of gallbladder volume changes on cystic duct resistance to both prograde (emptying) and retrograde (filling) steady-state flow was tested in 12 dogs under basal cholecystokinin-stimulated conditions utilizing a multiport catheter with a highly compliant balloon placed within the gallbladder fundus. Gallbladder volume was regulated by varying balloon volume from empty to just beyond physiologic distention. Cystic duct resistance was not affected by balloon volume under basal or stimulated conditions or by the direction of perfusate flow. This study demonstrated no relationship between gallbladder volume and cystic duct resistance and did not demonstrate a cystic duct sphincter mechanism at physiologic gallbladder volumes.

背景与目标： ：据我们所知，尚未研究胆囊体积与胆囊管功能之间的关系。我们假设胆囊体积的变化会影响胆囊管阻力。胆囊体积变化对胆囊管抵抗顺行（空）和逆行（充盈）稳态血流的影响在12条经基础胆囊收缩素刺激的狗中使用多端口导管，并在胆囊内放置高度顺应性球囊进行了测试。胆囊体积的调节是通过将气囊体积从空变到生理上的变化来进行的。囊性导管阻力不受基础或刺激条件下的球囊容积或灌注液流向的影响。这项研究表明胆囊体积和胆囊管阻力之间没有关系，并且在生理胆囊体积上也没有证明胆囊括约肌的机制。

BACKGROUND & AIMS: :A study in mice suggests that macrophages produce resistance to checkpoint inhibitors by removing anti-PD-1 antibodies from T cells. Fcγ receptors on macrophages bind to the Fc domain on the antibodies. Blocking this interaction with other antibodies produced dramatic tumor shrinkage in mice.

背景与目标： ：在小鼠中的一项研究表明，巨噬细胞通过从T细胞中去除抗PD-1抗体来产生对检查点抑制剂的抗性。巨噬细胞上的Fcγ受体与抗体上的Fc结构域结合。阻断与其他抗体的这种相互作用会在小鼠中产生明显的肿瘤缩小。

BACKGROUND & AIMS: :Currently, rolling resistance and wheelchair stability during manual wheelchair propulsion can be assessed from the loads applied on the front and rear wheels, which are determined in a static condition. However, a user's actions on the wheelchair would change these loads during locomotion, which should affect both the rolling resistance and wheelchair stability. The goal of this study was to verify these assumptions and assess how much the rolling resistance and wheelchair stability are affected by the user's actions during propulsion. For that purpose, a mechanical model was developed using measurements of an instrumented wheelchair equipped with several six-component dynamometers. Experiments were performed by three subjects propelling the instrumented wheelchair over flat ground. The results showed variations over wide ranges of the fore-aft distribution of the total load, rolling resistance, wheelchair stability, wheelchair velocity and mechanical power dissipated by the rolling resistance during the propulsion cycle. In addition, the time courses of all these variables differed with the subject. Finally, this study demonstrated the possibility of assessing intra-cycle values of both rolling resistance and wheelchair stability during manual wheelchair displacements in the field, which provides a technical step towards evaluating a wheelchair user in his daily environment.

背景与目标： ：目前，可以通过在静态条件下确定的前后轮负载来评估手动轮椅推进过程中的滚动阻力和轮椅稳定性。但是，使用者在轮椅上的动作会在运动过程中改变这些负荷，这将同时影响滚动阻力和轮椅稳定性。这项研究的目的是验证这些假设，并评估用户在推进过程中的动作对滚动阻力和轮椅稳定性的影响。为此，使用配备了数个六分量测功机的器械轮椅的测量结果建立了机械模型。由三名受试者将实验轮椅推到平坦的地面上进行了实验。结果显示，在推进周期内，总载荷的前后分布，滚动阻力，轮椅稳定性，轮椅速度和由滚动阻力耗散的机械动力的变化范围很大。此外，所有这些变量的时间过程都与主题不同。最后，这项研究证明了在野外手动轮椅移动期间评估滚动阻力和轮椅稳定性的周期内值的可能性，这为评估轮椅使用者的日常环境提供了技术上的一步。

BACKGROUND & AIMS: :Arginine supplements were given to 6 week old CBA mice beginning 3 days prior to inoculation with a murine sarcoma virus, the Moloney Sarcoma Virus (MSV). Although the basal diet contained 1.8% arginine and was therefore not arginine-deficient, supplementation of the diet and the drinking water with 0.5% arginine HCl reduced tumor incidence, lengthened the latency period, decreased tumor size, and hastened tumor regression. Arginine also increased thymic weight and cellularity in normal and in MSV-inoculated mice. The antitumor action of arginine may be related to its effect on the thymus.

背景与目标： ：在接种鼠肉瘤病毒莫洛尼肉瘤病毒（MSV）之前3天，向6周大的CBA小鼠补充精氨酸。尽管基础饮食中含有1.8％的精氨酸，因此并非精氨酸缺乏，但饮食和饮用水中添加0.5％的精氨酸HCl可以降低肿瘤的发生率，延长潜伏期，减小肿瘤的大小并加速肿瘤的消退。精氨酸还增加了正常小鼠和接种MSV的小鼠的胸腺重量和细胞数量。精氨酸的抗肿瘤作用可能与其对胸腺的作用有关。

BACKGROUND & AIMS: AIMS:To evaluate the prevalence and antimicrobial resistance of Enterococcus species from chickens and pigs in Beijing and Shandong Province, China. METHODS AND RESULTS:Swab samples were collected from four farms in Beijing and two in Shandong Province in 2009 and tested for Enterococcus. Minimum inhibitory concentrations of antimicrobial agents were determined using broth microdilution or agar screening methods. A total of 453 Enterococcus isolates were recovered, belonging to six different Enterococcus species. All isolates were sensitive to vancomycin. Resistance to tetracycline (92.5%), amikacin (89.4%), erythromycin (72.8%) and rifampin (58.1%), and high-level streptomycin resistance (HLSR, 50.3%) were prevalent, while resistance to penicillins (7.9% to penicillin and 4.2% to ampicillin) was rare. The resistance rates to phenicols (chloramphenicol and florfenicol) and enrofloxacin, and high-level gentamicin resistance (HLGR) were approximately 30%. The vast majority of the Enterococcus isolates were classified as multidrug-resistant organisms. CONCLUSIONS:Resistance of Enterococcus sp. to most antimicrobials was more prevalent in China than in European or other Asian countries. SIGNIFICANCE AND IMPACT OF THE STUDY:Our findings reveal a high level of antimicrobial resistance in Enterococcus isolates from food animals in China and underline the need for prudent use of antibiotics in chicken and pig production to minimize the spread of antibiotic-resistant enterococci.

背景与目标： 目的：评估北京和山东省鸡和猪的肠球菌的流行情况和耐药性。
方法与结果：2009年从北京的四个农场和山东的两个农场收集了拭子样本，并进行了肠球菌检测。使用肉汤微量稀释或琼脂筛选方法确定最小抑菌浓度。总共回收了453种肠球菌分离株，属于6种不同的肠球菌。所有分离株均对万古霉素敏感。对四环素（92.5％），丁胺卡那霉素（89.4％），红霉素（72.8％）和利福平（58.1％）以及高水平链霉素耐药性（HLSR，50.3％）的耐药性普遍存在，而对青霉素的耐药性（对青霉素的耐药性为7.9％）和氨苄西林占4.2％）是罕见的。对苯甲酚（氯霉素和氟苯尼考）和恩诺沙星的耐药率以及对庆大霉素的高耐药率（HLGR）约为30％。绝大多数肠球菌分离株被归类为耐多药生物。
结论：肠球菌的抗性与欧洲或其他亚洲国家相比，大多数抗菌药物在中国的流行程度更高。
研究的意义和影响：我们的发现表明，中国食用动物肠球菌分离株具有很高的抗药性，并强调在鸡和猪的生产中需要谨慎使用抗生素，以最大程度地减少对抗生素耐药的肠球菌的传播。

BACKGROUND & AIMS: :The leaves of «moderately hardy» (spinach), «very hardy» (ivy) and «extremely hardy» (spruce) plants [classification according to Levitt {1980)] show characteristic differences with respect to changes in membrane lipid composition and chloroplast ultrastructure which are correlated with the degree of the frost resistance achieved by each type of tissue during adaptation to sub-zero temperatures. Spinach leaves showed no increase in their total lipid content upon frost hardening. On the contrary, the amount of galactolipids decreased considerably, whereas that of phospholipids only slightly increased. No shift from the saturated palmitic acid to the three-fold unsaturated linolenic acid was observed. The membrane lipid content of ivy leaves and spruce needles increased to a similar extent during frost hardening. However, in contrast to spruce needles, a distinct preferential accumulation of the phospholipids was observed in ivy leaves, resulting in an increased PL/GL ratio. A considerable shift from saturated (palmitic) to unsaturated fatty acids was detected in both plants, due mainly to an increase in the proportion of linoleic acid in ivy and of linolenic acid in spruce. In spite of the considerable increase in lipid content, no increase in chloroplast number per cell could be detected in ivy leaves, although the length of the thylakoids was nearly doubled and the plastids appeared to be in a division stage: however, no real division could ever be observed. On the contrary, an increase in the number of chloroplasts and mitochondria was observed in spruce needles. Membrane augmentation became further evident by the many large invaginations of the chloroplast envelope formed when the frost-hardened leaves of ivy or spruce were exposed to sub-zero temperatures which they could just survive.

背景与目标： ：“中等硬度”（菠菜），“极度坚硬”（ivy）和“极度坚硬”（云杉）植物的叶子[根据Levitt（1980）分类）在膜脂成分和叶绿体变化方面表现出特征差异超微结构，与适应零度以下温度时每种组织的抗冻性程度有关。霜冻硬化后，菠菜叶的总脂质含量没有增加。相反，半乳糖脂的量显着减少，而磷脂的量仅略有增加。没有观察到从饱和的棕榈酸到三倍的不饱和亚麻酸的转变。在霜冻硬化过程中，常春藤叶和云杉针的膜脂含量增加了相似的程度。然而，与云杉针头相反，在常春藤叶中观察到磷脂的明显优先积累，从而导致PL / GL比增加。在这两种植物中均检测到从饱和（棕榈酸）到不饱和脂肪酸的显着变化，这主要是由于常春藤中亚油酸和云杉中亚麻酸的比例增加。尽管脂质含量显着增加，但常春藤叶中未检测到每细胞的叶绿体数量增加，尽管类囊体的长度几乎增加了一倍，质体似乎处于分裂阶段：但是，不能进行真正的分裂曾经被观察到。相反，在云杉针头中观察到叶绿体和线粒体数量增加。当常春藤或云杉的冻干叶子暴露于零度以下的温度下就可以生存时，叶绿体包膜的许多大的浸入使膜的增强变得更加明显。