BACKGROUND & AIMS: BACKGROUND AND PURPOSE:The purpose of this project was to create guidelines for 13 types of physical rehabilitation interventions used in the management of adult patients (>18 years of age) presenting with hemiplegia or hemiparesis following a single clinically identifiable ischemic or hemorrhagic cerebrovascular accident (CVA). METHOD:Using Cochrane Collaboration methods, the Ottawa Methods Group identified and synthesized evidence from comparative controlled trials. The group then formed an expert panel, which developed a set of criteria for grading the strength of the evidence and the recommendation. Patient-important outcomes were determined through consensus, provided that these outcomes were assessed with a validated and reliable scale. RESULTS:The Ottawa Panel developed 147 positive recommendations of clinical benefit concerning the use of different types of physical rehabilitation interventions involved in post-stroke rehabilitation. DISCUSSION AND CONCLUSION:The Ottawa Panel recommends the use of therapeutic exercise, task-oriented training, biofeedback, gait training, balance training, constraint-induced movement therapy, treatment of shoulder subluxation, electrical stimulation, transcutaneous electrical nerve stimulation, therapeutic ultrasound, acupuncture, and intensity and organization of rehabilitation in the management of post stroke.

背景与目标：

BACKGROUND & AIMS: :The goal of this study was to establish and validate a protocol for preparing bovine cardiomyocytes from slaughterhouse material for nuclear transfer experiments. The cardiomyocyte was selected because it is a terminally differentiated cell and strongly expresses a unique subset of genes which can be monitored during the reprogramming period. A total of 39 trials were conducted, and an optimized protocol was developed yielding individual contractile cardiomyocytes from 3-5-month-old bovine fetuses The basic protocol involves stabilization of bovine heart tissue for transportation from the slaughterhouse to the laboratory by perfusion with Custodiol. This was followed by an enzymatic dissociation with collagenase in calcium-free medium and yielded individual contractile rod-shaped cardiomyocytes. Subsequent addition of Ca2+ caused the cardiomyocytes to round up which was an essential pre-condition for drawing them into glass transfer pipettes for delivery into the perivitelline space and for efficient electrofusion with cytoplasts derived from in vitro matured bovine oocytes. The use of cardiomyocytes maintained at 37 degrees C in nuclear transfer, resulted in a significantly reduced proportion of blastocysts compared to adult fibroblasts (14.0% versus 32.7%). Storage of cardiomyocytes at 4 degrees C prior to nuclear transfer was not compatible with blastocyst development. It is expected that this system will be valuable for investigating the reprogramming of gene expression which occurs after somatic cell nuclear transfer.

背景与目标： : 这项研究的目的是建立和验证从屠宰场材料中制备牛心肌细胞以进行核移植实验的协议。选择心肌细胞是因为它是终末分化的细胞，并且强烈表达可以在重编程期间监测的独特基因子集。总共进行了39项试验，并开发了一种优化的方案，从3-5个月大的牛胎儿中产生了单个收缩心肌细胞。基本方案涉及稳定牛心脏组织，以便通过灌注从屠宰场运输到实验室。保管二醇。随后在无钙培养基中与胶原酶酶解离，并产生单个收缩的杆状心肌细胞。随后添加Ca2会导致心肌细胞四舍五入，这是将其吸入玻璃转移移液管以输送到卵黄周围空间以及与来自体外成熟牛卵母细胞的细胞质进行有效电融合的必要前提。与成人成纤维细胞相比，在核转移中使用维持在37 ℃ 的心肌细胞导致胚泡的比例显著降低 (14.0% 对32.7%)。在核转移之前在4摄氏度下储存心肌细胞与胚泡发育不相容。预计该系统对于研究体细胞核移植后发生的基因表达的重编程将很有价值。

BACKGROUND & AIMS: BACKGROUND:Many apparently disparate risk factors have been implicated as causes of eating disorders. This study was designed to test the hypothesis that 2 broad classes of risk factors exist for bulimia nervosa: those that increase the risk for development of a psychiatric disorder in general and those that increase the risk of dieting. It was predicted that the latter are especially common among persons with bulimia nervosa.

METHODS:A case-control design was used involving 2 integrated comparisons. First, 102 subjects with bulimia nervosa were compared with 204 healthy control subjects without an eating disorder. Second, the same 102 subjects with bulimia nervosa were compared with 102 subjects with other psychiatric disorders. To reduce sampling bias, the subjects were recruited directly from the community. A broad range of putative risk factors was assessed.

RESULTS:The subjects with bulimia nervosa and the healthy control subjects differed in their rates of exposure to most of the putative risk factors. Far fewer differences were evident between the subjects with bulimia nervosa and the control subjects with other psychiatric disorders, although exposure to factors that were likely to increase the risk of dieting and to negative self-evaluation and certain parental problems (including alcohol use disorder) were substantially more common among those with bulimia nervosa.

CONCLUSIONS:The findings support the hypothesis that bulimia nervosa is the result of exposure to general risk factors for psychiatric disorder and risk factors for dieting. An unexpected finding was the particularly high rates of premorbid negative self-evaluation and certain parental problems among those with bulimia nervosa.

背景与目标： 背景 : 许多明显不同的危险因素被认为是饮食失调的原因。这项研究旨在检验以下假设: 神经性贪食症存在两大类危险因素: 通常增加精神疾病发展风险的因素和增加节食风险的因素。据预测，后者在神经性贪食症患者中尤其常见。
方法 : 使用了涉及2个综合比较的病例对照设计。首先，将102名患有神经性贪食症的受试者与204名没有进食障碍的健康对照受试者进行比较。其次，将患有暴食症的相同102受试者与患有其他精神疾病的102受试者进行比较。为了减少抽样偏差，直接从社区招募了受试者。评估了广泛的推定危险因素。
结果 : 患有神经性贪食症的受试者和健康对照受试者在暴露于大多数推定危险因素的比率上有所不同。神经性贪食症的受试者与其他精神疾病的对照受试者之间的差异要少得多，尽管暴露于可能增加节食风险的因素以及负面的自我评估和某些父母问题 (包括酒精使用障碍) 在神经性贪食症患者中更为普遍。
结论 : 研究结果支持以下假设: 神经性贪食症是暴露于精神疾病的一般危险因素和节食的危险因素的结果。一个意想不到的发现是，在神经性贪食症患者中，病前负面自我评估和某些父母问题的发生率特别高。

BACKGROUND & AIMS: OBJECTIVE:The goal of this study was to develop an improved (62)Zn/(62)Cu generator based on cation exchange resin and remote preparation at high radioactivity scale for clinical use. METHODS:A natural Cu target was irradiated with proton beam in the energy range of 30-->19 MeV at a beam current of 10 muA for 1 h to obtain around 1.7 GBq of (62)Zn. The (62)Zn was isolated from the Cu target on an anion exchange column with more than 97% yield within 2.5 h from the EOB. The (62)Zn/(62)Cu generator was prepared by loading the (62)Zn(2+) on a Sep-Pak plus CM cartridge. RESULTS:The generator showed high elution efficiency ( approximately 96%) using a small volume (ca. 3 ml) of a 200-mM glycine solution with a very low breakthrough of (62)Zn (<0.1%). CONCLUSIONS:This (62)Zn/(62)Cu generator has been proven to be highly useful as a source of (62)Cu for the synthesis of (62)Cu-labeled compounds. The clinical application of [(62)Cu]Cu-ATSM produced with this generator has been already approved by the Institutional Review Board at the National Institute of Radiological Sciences.

背景与目标：

BACKGROUND & AIMS: :Iminodisuccinate (IDS) epimerase catalyzes the epimerisation of R,R-, S,S- and R,S- iminodisuccinate, one step in the biodegradation of the chelating agent iminodisuccinate by Agrobacterium tumefaciens BY6. The enzyme is a member of the MmgE/PrpD protein family, a diverse and little characterized class of proteins of prokaryotic and eukaryotic origin. IDS epimerase does not show significant overall amino acid sequence similarity to any other protein of known three-dimensional structure. The crystal structure of this novel epimerase has been determined by multi-wavelength diffraction to 1.5 A resolution using selenomethionine-substituted enzyme. In the crystal, the enzyme forms a homo-dimer, and the subunit consists of two domains. The larger domain, not consecutive in sequence and comprising residues Met1-Lys266 and Leu400-Pro446, forms a novel all alpha-helical fold with a central six-helical bundle. The second, smaller domain folds into an alpha+beta domain, related in topology to chorismate mutase by a circular permutation. IDS epimerase is thus not related in three-dimensional structure to other known epimerases. The fold of the IDS epimerase is representative for the whole MmgE/PrpD family. The putative active site is located at the interface between the two domains of the subunit, and is characterized by a positively charged surface, consistent with the binding of a highly negatively charged substrate such as iminodisuccinate. Docking experiments suggest a two-base mechanism for the epimerisation reaction.

背景与目标： : 亚氨基二琥珀酸酯 (IDS) 差向异构化催化R，R-，S，S-和R，S-亚氨基二琥珀酸酯的差向异构化，这是根癌农杆菌对螯合剂亚氨基二琥珀酸酯生物降解的第一步。该酶是MmgE/PrpD蛋白家族的成员，MmgE/PrpD蛋白家族是原核和真核来源的多种多样且特征很少的蛋白质。IDS差向异构酶与已知三维结构的任何其他蛋白质没有显示出明显的总体氨基酸序列相似性。该新型差向异构酶的晶体结构已通过多波长衍射确定，以使用硒代蛋氨酸取代的酶1.5分辨率。在晶体中，酶形成同型二聚体，亚基由两个结构域组成。较大的结构域不是连续的并且包含Met1-Lys266和Leu400-Pro446的残基，形成具有中心六螺旋束的新型全 α-螺旋折叠。第二个较小的结构域折叠成 α β 结构域，在拓扑上通过环状排列与脉络酸突变酶有关。因此，IDS差向异构酶在三维结构上与其他已知的差向异构酶无关。IDS差向异构酶的折叠代表整个MmgE/PrpD家族。推定的活性位点位于亚基的两个结构域之间的界面处，其特征在于带正电的表面，与高度带负电的底物 (例如亚氨基二琥珀酸酯) 的结合一致。对接实验提出了向异构化反应的两基机制。

BACKGROUND & AIMS: :A computer program is presented which determines the secondary structure of linear RNA molecules by simulating a hypothetical process of folding. This process implies the concept of 'nucleation centres', regions in RNA which locally trigger the folding. During the simulation, the RNA is allowed to fold into pseudoknotted structures, unlike all other programs predicting RNA secondary structure. The simulation uses published, experimentally determined free energy values for nearest neighbour base pair stackings and loop regions, except for new extrapolated values for loops larger than seven nucleotides. The free energy value for a loop arising from pseudoknot formation is set to a single, estimated value of 4.2 kcal/mole. Especially in the case of long RNA sequences, our program appears superior to other secondary structure predicting programs described so far, as tests on tRNAs, the LSU intron of Tetrahymena thermophila and a number of plant viral RNAs show. In addition, pseudoknotted structures are often predicted successfully. The program is written in mainframe APL and is adapted to run on IBM compatible PCs, Atari ST and Macintosh personal computers. On an 8 MHz 8088 standard PC without coprocessor, using STSC APL, it folds a sequence of 700 nucleotides in one and a half hour.

背景与目标： : 提出了一种计算机程序，该程序通过模拟假想的折叠过程来确定线性RNA分子的二级结构。此过程暗示了 “成核中心” 的概念，即RNA中局部触发折叠的区域。在模拟过程中，与所有其他预测RNA二级结构的程序不同，允许RNA折叠成假结结构。模拟使用已发布的，实验确定的最近邻碱基对堆叠和环区域的自由能值，但大于七个核苷酸的环的新外推值除外。由假结形成产生的环的自由能值被设置为4.2 kcal/mole的单个估计值。特别是在长RNA序列的情况下，我们的程序似乎优于迄今为止描述的其他二级结构预测程序，如对trna，嗜热四膜虫的LSU内含子和许多植物病毒RNA的测试所示。此外，伪结网结构通常被成功预测。该程序以大型机APL编写，并适用于在IBM兼容pc，Atari ST和Macintosh个人计算机上运行。在没有协处理器的8 mhz 8088标准PC上，使用stscapl，它在一个半小时内折叠700个核苷酸的序列。

BACKGROUND & AIMS: :Although associated with all plants, fungal endophytes (microfungi that live within healthy plant tissues) represent an unknown proportion of fungal diversity. While there is a growing appreciation of their ecological importance and human uses, little is known about their host specificity, geographic structure, or phylogenetic relationships. We surveyed endophytic Ascomycota from healthy photosynthetic tissues of three plant species (Huperzia selago, Picea mariana, and Dryas integrifolia, representing lycophytes, conifers, and angiosperms, respectively) in northern and southern boreal forest (Québec, Canada) and arctic tundra (Nunavut, Canada). Endophytes were recovered from all plant species surveyed, and were present in <1-41% of 2 mm2 tissue segments examined per host species. Sequence data from the nuclear ribosomal internal transcribed spacer region (ITS) were obtained for 280 of 558 isolates. Species-accumulation curves based on ITS genotypes remained non-asymptotic, and bootstrap analyses indicated that a large number of genotypes remain to be found. The majority of genotypes were recovered from only a single host species, and only 6% of genotypes were shared between boreal and arctic communities. Two independent Bayesian analyses and a neighbor-joining bootstrapping analysis of combined data from the nuclear large and small ribosomal subunits (LSUrDNA, SSUrDNA; 2.4 kb) showed that boreal and arctic endophytes represent Dothideomycetes, Sordariomycetes, Chaetothyriomycetidae, Leotiomycetes, and Pezizomycetes. Many well-supported phylotypes contained only endophytes despite exhaustive sampling of available sequences of Ascomycota. Together, these data demonstrate greater than expected diversity of endophytes at high-latitude sites and provide a framework for assessing the evolution of these poorly known but ubiquitous symbionts of living plants.

背景与目标： : 尽管与所有植物相关，但真菌内生菌 (生活在健康植物组织中的微真菌) 代表了未知的真菌多样性比例。尽管人们越来越认识到它们的生态重要性和人类用途，但对它们的宿主特异性，地理结构或系统发育关系知之甚少。我们调查了北部和南部北方森林 (加拿大魁北克) 和北极苔原 (加拿大努纳武特) 中三种植物 (石杉，云杉，马里亚纳云杉和干草) 的健康光合组织中的内生子囊菌。从调查的所有植物物种中回收内生菌，并且存在于每个宿主物种检查的2平方毫米个组织节段的 <1-41% 中。从核核糖体内部转录间隔区 (ITS) 获得280 558分离株的序列数据。基于其基因型的物种积累曲线仍然是非渐近的，并且bootstrap分析表明仍有大量基因型有待发现。大多数基因型仅从单个宿主物种中回收，并且在北方和北极社区之间仅共享6% 基因型。对来自核大核糖体亚基和小核糖体亚基 (LSUrDNA，SSUrDNA; 2.4 kb) 的合并数据进行了两次独立的贝叶斯分析和邻居连接的自举分析，结果表明，北方和北极内生菌代表独生菌，蛇纹菌，Chaetothyriomycetidae，Leotiomycetes和Pezizomycetes。尽管对子囊菌门的可用序列进行了详尽的采样，但许多支持良好的系统型仅包含内生菌。总之，这些数据证明了高纬度地点内生植物的多样性大于预期，并为评估这些鲜为人知但无处不在的生物共生体的进化提供了一个框架。

BACKGROUND & AIMS: :The aim of this study was to examine the different patterns of cerebellar and/or brainstem atrophy in spinocerebellar ataxia (SCA) type 3 and 6. Eighteen patients (SCA3 n=9, SCA6 n=9) and 15 healthy volunteers were studied. Voxel-based morphometry (VBM) was applied to segmented grey matter (GM) and white matter (WM) of high-resolution T1-weighted brain volumes of each group. We found reduction of grey matter in the pons as well as in the vermis in SCA3 as compared to control subjects. In SCA6 significant grey matter loss was found in hemispheric lobules bilaterally as well as in the vermis. White matter analysis revealed significant changes in SCA3, especially in the pons, in the white matter surrounding the dentate nucleus (DN) and in the cerebellar peduncles, whereas no significant white matter reduction was found in SCA6 patients. Our results demonstrate different patterns of grey and white matter affection detected by magnetic resonance imaging (MRI) in SCA3 and SCA6 patients, confirming the pathological concept of cortical cerebellar atrophy in SCA6. In contrast, SCA3 represents a form of ponto-cerebellar atrophy with predominant affection of pontine nuclei and fibre tracts.

背景与目标： : 这项研究的目的是检查3型和6型脊髓小脑共济失调 (SCA) 的小脑和/或脑干萎缩的不同模式。研究了18名患者 (SCA3 n = 9，SCA6 n = 9) 和15名健康志愿者。将基于体素的形态计量学 (VBM) 应用于每组高分辨率T1-weighted脑体积的分段灰质 (GM) 和白质 (WM)。与对照组相比，我们发现SCA3中的脑桥和ver中的灰质减少。在SCA6中，双侧半球小叶以及ver骨中都发现了明显的灰质损失。白质分析显示SCA3发生了显着变化，尤其是在脑桥，齿状核 (DN) 周围的白质和小脑梗中，而在SCA6患者中未发现明显的白质减少。我们的结果表明，通过磁共振成像 (MRI) 在SCA3和SCA6患者中检测到的灰质和白质的不同模式，证实了SCA6中皮质小脑萎缩的病理概念。相反，SCA3代表一种桥小脑萎缩的形式，主要影响桥脑核和纤维束。

BACKGROUND & AIMS: :Glucosamine- and N-acetyl glucosamine-containing polymers are being used in an increasing number of biomedical applications, including in products for surface (topical) hemostasis. The studies presented here investigate the relationship between the structure (conformation) and function (activation of hemostasis) of glucosamine-based materials. Several polymer systems were studied, including fibers isolated from a microalgal source containing poly-N-acetyl glucosamine polymers that are organized in a parallel, hydrogen-bonded tertiary structure and can be chemically modified to an antiparallel orientation; and gel formulation derivatives of the microalgal fibers consisting of partially deacetylated (F2 gel) and fully deacetylated (F3 gel) polymers. Comparison of the properties of the poly-N-acetyl glucosamine fiber-derived materials with chitin, chitosan, and commercial chitosan-based products are presented. Several studies were performed with the glucosamine-based materials, including (1) an analysis of the ability of materials to activate platelets and turnover of the intrinsic coagulation cascade, (2) an examination of the viscoelastic properties of mixtures of platelet-rich plasma and the glucosamine-based materials via thromboelastography, and (3) scanning electron microscopic studies to examine the morphology of the glucosamine-based materials. The results presented demonstrate that hemostatic responses to the glucosamine-based materials studied are highly dependent on their chemical nature and tertiary/quaternary structure. The unique natural microalgal fibers were found to have strongly prohemostatic activity compared to the other materials studied.

背景与目标： : 含氨基葡萄糖和N-乙酰氨基葡萄糖的聚合物正在越来越多的生物医学应用中使用，包括用于表面 (局部) 止血的产品。此处介绍的研究研究了基于氨基葡萄糖的材料的结构 (构象) 和功能 (止血的激活) 之间的关系。研究了几种聚合物体系，包括从微藻源分离的纤维，该微藻源含有聚-N-乙酰基葡糖胺聚合物，这些聚合物以平行的氢键合三级结构组织，可以化学改性为反平行取向; 和微藻纤维的凝胶制剂衍生物由部分脱乙酰化 (F2凝胶) 和完全脱乙酰化 (F3凝胶) 聚合物组成。比较了聚N-乙酰氨基葡萄糖纤维衍生材料与几丁质，壳聚糖和市售基于壳聚糖的产品的性能。使用基于氨基葡萄糖的材料进行了几项研究，包括 (1) 分析材料激活血小板的能力和内在凝血级联的周转，(2) 通过血栓弹力图检查富含血小板的血浆和基于氨基葡萄糖的材料的混合物的粘弹性，(3) 扫描电子显微镜研究以检查基于氨基葡萄糖的材料的形态。给出的结果表明，对所研究的基于氨基葡萄糖的材料的止血反应高度依赖于它们的化学性质和三级/四级结构。与研究的其他材料相比，发现独特的天然微藻纤维具有很强的止血活性。

BACKGROUND & AIMS: OBJECTIVE:The 24-hour creatinine clearance is the standard clinical technique for measuring kidney function; however, this measurement is cumbersome and inconvenient for patients. We hypothesized that a camera-based technetium-99m mercaptoacetyltriglycine (MAG3) clearance obtained simultaneously with a standard MAG3 scan would correlate well with the 24-hour creatinine clearance and could serve as a simple marker of kidney function. MATERIALS AND METHODS:Data were obtained from a retrospective analysis of 28 patients with varying degrees of kidney dysfunction and 85 subjects evaluated for kidney donation. The MAG3 clearance was calculated using a camera-based technique without blood or urine sampling. The creatinine clearance was measured using the plasma creatinine and a 24-hour urine collection. The MAG3 and creatinine clearances were corrected for body surface area, and clearance values in healthy subjects and patients were compared using the paired Student's t test. The linear association between the MAG3 and creatinine clearances was expressed by Pearson's correlation coefficient. RESULTS:The mean MAG3 clearance in the potential kidney donors was 321 +/- 95 mL/min/1.73 m2 (95% CI, 171-546 mL/min/1.73 m2), significantly higher than the mean creatinine clearance of 152 +/- 51 mL/min/1.73 m2 (79-278 mL/min/1.73 m2, p < 0.001). The mean MAG3 clearance in patients was 153 +/- 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2) and was also significantly higher than the mean creatinine clearance of 74 +/- 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2, p < 0.001). The ratio of the mean creatinine clearance to the mean MAG3 clearance was essentially the same for volunteers and patients, 0.47 and 0.48, respectively. The Pearson's correlation between the MAG3 and creatinine clearances was 0.80 (0.72-0.86). CONCLUSION:The camera-based 99mTc-MAG3 clearance correlates well with the 24-hour creatinine clearance and can provide a simple and convenient index of kidney function.

背景与目标：

BACKGROUND & AIMS: :Cyproheptadine is a drug that shows high affinity for type 2 (5-HT2) receptors. We studied a series of compounds obtained by modification of the tricyclic system of Cyp (dibenzocycloheptadiene): 2f (thioxanthene), 2g (xanthene), 2h (dihydrodibenzocycloheptadiene), 2j (diphenyl), 2i (fluorene), and 3b (phenylmethyl). Their activities at the rat cerebral cortex 5-HT2A receptor were (pKi +/- S.E.M.): 8.80 +/- 0.11 (Cyp), 8.60 +/- 0.07 (2f), 8.40 +/- 0.02 (2g), 8.05 +/- 0.03 (2h), 7.87 +/- 0.12 (2j), 6.70 +/- 0.02 (2i) and 6.45 +/- 0.02 (3b); those at the rat stomach fundus 5-HT2B receptor (pA2 +/- S.E.M.) were: 9.14 +/- 0.25 (Cyp), 8.49 +/- 0.07 (2f), 7.58 +/- 0.58 (2g), 7.02 +/- 0.14 (2h), 6.07 +/- 0.20 (2j), and undetectable (2i, 3b): and those at the pig choroidal plexus 5-HT2C receptor (pKi +/- S.E.M.) were: 8.71 +/- 0.08 (Cyp), 8.68 +/- 0.01 (2f), 8.58 +/- 0.20 (2g), 7.95 +/- 0.05 (2h), 7.57 +/- 0.04 (2j), 6.98 +/- 0.04 (2i) and 6.63 +/- 0.20 (3b). The slopes did not differ significantly from unity. The compounds exhibited the same order of activities at every type of receptor, and the most active molecules presented certain steric (butterfly conformation of the tricyclic system) and electrostatic (proton affinity on the top of the central rings) patterns. It is concluded that the activity of cyproheptadine derivatives at 5-HT2 receptors is related to these molecular features, which make feasible a common disposition to interact with all three 5-HT2 subtypes.

背景与目标： : 赛庚胺是一种对2型 (5-HT2) 受体显示高亲和力的药物。我们研究了通过修饰Cyp (二苯并环庚二烯) 的三环体系获得的一系列化合物: 2f (噻吩)，2g (xanthene)，2h (二氢二苯并环庚二烯)，2j (二苯基)，2i (芴) 和3b (苯基甲基)。它们在大鼠大脑皮层5-HT2A受体上的活性为 (pKi +/-s.e.M.): 8.80 +/- 0.11 (Cyp)，8.60 +/- 0.07 (2f)，8.40 +/- 0.02 (2g)，8.05 +/- 0.03 (2h)，7.87 +/- 0.12 (2j)，6.70 +/- 0.02 (2i) 和6.45 +/- 0.02 (3b); 大鼠胃底5-HT2B受体 (pA2 +/-s.e.M.) 为: 9.14 +/- 0.25 (Cyp)，8.49 +/- 0.07 (2f)，7.58 +/- 0.58 (2g)，7.02 +/- 0.14 (2h)，6.07 +/- 0.20 (2j) 和不可检测 (2i，3b): 猪脉络丛5-HT2C受体 (pKi +/-s.e.M.) 为: 8.71 +/- 0.08 (Cyp)，8.68 +/- 0.01 (2f)，8.58 +/- 0.20 (2g)，7.95 +/- 0.05 (2h) 、7.57 +/- 0.04 (2j) 、6.98 +/- 0.04 (2i) 和6.63 +/- 0.20 (3b)。坡度与统一没有显着差异。这些化合物在每种类型的受体上都表现出相同的活性顺序，并且最具活性的分子呈现某些空间 (三环系统的蝴蝶构象) 和静电 (中心环顶部的质子亲和力) 模式。结论是，赛庚胺衍生物在5-HT2受体上的活性与这些分子特征有关，这使得与所有三种5-HT2亚型相互作用的共同处置是可行的。

BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

背景与目标：

BACKGROUND & AIMS: :6-Pyruvoyltetrahydropterin synthase (PTPS) catalyzes the second step of tetrahydrobiopterin (BH4) synthesis. We previously identified PTPS orthologs (bPTPS-Is) in bacteria which do not produce BH4. In this study we disrupted the gene encoding bPTPS-I in Synechococcus sp. PCC 7942, which produces BH4-glucoside. The mutant was normal in BH4-glucoside production, demonstrating that bPTPS-I does not participate in BH4 synthesis in vivo and bringing us a new PTPS ortholog (bPTPS-II) of a bimodular polypeptide. The recombinant Synechococcus bPTPS-II was assayed in vitro to show PTPS activity higher than human enzyme. Further computational analysis revealed the presence of mono and bimodular bPTPS-II orthologs mostly in green sulfur bacteria and cyanobacteria, respectively, which are well known for BH4-glycoside production. In summary we found new bacterial PTPS orthologs, having either a single or dual domain structure and being responsible for BH4 synthesis in vivo, thereby disclosing all the bacterial PTPS homologs.

背景与目标： : 6-丙酮酸基四氢蝶呤合酶 (PTPS) 催化四氢生物蝶呤 (BH4) 合成的第二步。我们先前在不产生bh4的细菌中鉴定了PTPS直系同源物 (bPTPS-Is)。在这项研究中，我们破坏了Synechococcus sp. PCC 7942中编码bPTPS-I的基因，该基因产生了BH4-glucoside。该突变体在BH4-glucoside生产中是正常的，表明bPTPS-I在体内不参与BH4合成，并为我们带来了双峰多肽的新PTPS直系同源物 (bPTPS-II)。在体外测定了重组Synechococcus bptp-II，显示PTPS活性高于人酶。进一步的计算分析表明，分别在绿色硫细菌和蓝细菌中存在单和双模bPTPS-II直系同源物，这在BH4-glycoside生产中是众所周知的。总而言之，我们发现了新的细菌PTPS直系同源物，具有单个或双结构域结构，并负责体内BH4的合成，从而公开了所有细菌PTPS同源物。

BACKGROUND & AIMS: :The role of carbohydrate in the antigenic and immunogenic structure of bovine herpesvirus type 1 (BHV-1) glycoproteins gI and gIV was investigated. Deglycosylated proteins induced a significantly lower antibody response in rabbits than native glycoproteins suggesting that the immunogenicity of several epitopes on gI and gIV is carbohydrate-dependent. Loss of carbohydrate from gI also resulted in a significantly decreased ability to induce a serum neutralizing antibody response to BHV-1, due to modifications in three distinct carbohydrate-containing continuous epitopes. Similarly, in vitro lysis of BHV-1-infected cells was significantly reduced when antibodies raised against deglycosylated gI were employed; this was attributed to changes in two of the three carbohydrate-dependent neutralizing epitopes on gI. The oligosaccharides may be directly involved as actual components of these continuous epitopes, rather than in stabilization of the conformation of the protein. In contrast, carbohydrate removal from gIV did not have a significant effect on the capacity to stimulate a neutralizing antibody response. Accordingly, none of the neutralizing epitopes on gIV appeared to be carbohydrate-dependent. Similarly, lysis of virus-infected cells was not significantly reduced when antibodies specific for deglycosylated rather than native gIV were used. In contrast to the humoral response, the delayed-type hypersensitivity response was stronger in rabbits immunized with deglycosylated proteins than in those inoculated with native glycoproteins gI or gIV. Consequently, the carbohydrates on gI and gIV may play a dual role in the host's immune recognition and response by contributing to certain epitopes, but masking others. The implications for the development of a subunit vaccine against BHV-1 are discussed.

背景与目标： : 研究了碳水化合物在牛疱疹病毒1型 (BHV-1) 糖蛋白gI和gIV的抗原性和免疫原性结构中的作用。与天然糖蛋白相比，去糖基化蛋白诱导的兔抗体反应明显降低，这表明gI和gIV上几个表位的免疫原性是碳水化合物依赖性的。由于三个不同的含碳水化合物的连续表位的修饰，gI中碳水化合物的损失还导致诱导血清中和抗体对BHV-1的反应的能力显着降低。同样，当使用抗去糖基化gI的抗体时，BHV-1-infected细胞的体外裂解显着减少; 这归因于gI上三个碳水化合物依赖性中和表位中的两个的变化。寡糖可能直接作为这些连续表位的实际成分参与，而不是稳定蛋白质的构象。相反，从gIV中去除碳水化合物对刺激中和抗体反应的能力没有显着影响。因此，gIV上的中和表位似乎都不是碳水化合物依赖性的。同样，当使用对去糖基化而非天然gIV具有特异性的抗体时，病毒细胞的裂解也没有显着减少。与体液反应相反，用去糖基化蛋白免疫的兔子的迟发型超敏反应比用天然糖蛋白gI或gIV接种的兔子更强。因此，gI和gIV上的碳水化合物可能通过促进某些表位而在宿主的免疫识别和反应中起双重作用，但掩盖了其他表位。讨论了开发针对BHV-1的亚单位疫苗的意义。

BACKGROUND & AIMS: We have used 600 MHz 1H NMR spectroscopy data to determine the solution structure of a 31-residue domain of a murine class II major histocompatibility (MHC) protein. This domain, I-Ab(beta)-(60-90), binds to the superantigen staphylococcal enterotoxin A. Distance geometry and dynamical simulated annealing calculations were performed using NOESY- and COSY-deduced constraints. I-Ab(beta)-(60-90), which is mostly alpha-helical, is more similar to the corresponding region of the class II MHC protein HLA-DR1 than to the class I MHC protein HLA-A2. Arg-72 and Arg-80 lie on the same side of the helix and face away from the antigenic peptide binding groove. His-81, implicated in both superantigen and peptide binding, is located midway between the surface defined by Arg-72/Arg-80 and residues that define the inside of the peptide binding groove, allowing for its participation in both types of binding.

背景与目标： 我们使用了600 MHz 1H NMR光谱数据来确定鼠II类主要组织相容性 (MHC) 蛋白的31残基结构域的溶液结构。该结构域I-Ab(beta)-(60-90) 与超抗原葡萄球菌肠毒素A结合。使用NOESY和COSY推导的约束进行距离几何和动态模拟退火计算。I-Ab (β)-(60-90)，其主要是 α-螺旋的，比I类MHC蛋白HLA-DR1的相应区域更类似于I类MHC蛋白HLA-A2。Arg-72和Arg-80位于螺旋的同一侧，并远离抗原肽结合槽。His-81与超抗原和肽结合有关，位于由Arg-72/Arg-80定义的表面和定义肽结合凹槽内部的残基之间的中间，允许其参与两种类型的结合。