• 【Dlx同源盒基因在鳃弓的远端模式中的作用: Dlx-1,Dlx-2和Dlx-1的突变,以及-2改变了源自第一和第二弓的近端骨骼和软组织结构的形态发生。】 复制标题 收藏 收藏
    DOI:10.1006/dbio.1997.8556 复制DOI
    作者列表:Qiu M,Bulfone A,Ghattas I,Meneses JJ,Christensen L,Sharpe PT,Presley R,Pedersen RA,Rubenstein JL
    BACKGROUND & AIMS: The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.

    背景与目标: Dlx同源盒基因家族在胚胎颅面外胚层和外胚间质中以复杂的模式表达。先前的研究表明,Dlx-2对于鼠第一和第二鳃弓近端区域的发育至关重要。在这里,我们描述了具有Dlx-1和-2突变的小鼠的颅面表型。对具有Dlx-1和-2突变的小鼠的骨骼和软组织分析提供了额外的证据,表明Dlx基因调节鳃弓的近端模式。此分析还阐明了Dlx-1和Dlx-2在颅面发育中的独特和重叠作用。此外,缺少Dlx-1和-2的小鼠具有独特的异常,包括缺少上颌磨牙。Dlx-1和-2在近侧和远侧第一和第二拱形中表达,但只有近侧区域是异常的。Dlx-1、-2、-3、-5和-6的嵌套表达模式为预测每个基因的区域特异性需求的模型提供了证据。最后,Dlx-2和Dlx-1和-2突变体具有异位的头骨成分,类似于在系统发育上更原始的脊椎动物中发现的骨骼和软骨。
  • 【疾病机制: 2型糖尿病的肝脂肪变性-发病机制和临床意义。】 复制标题 收藏 收藏
    DOI:10.1038/ncpendmet0190 复制DOI
    作者列表:Roden M
    BACKGROUND & AIMS: :Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.
    背景与目标: : 肝脂肪变性是由肝细胞脂质 (HCLs) 含量增加定义的,在胰岛素抵抗状态 (包括2型糖尿病) 中经常观察到。饮食中过量的饱和脂肪会显着促进HCL的积累。HCL水平升高主要是导致肝胰岛素抵抗的原因,这可能是由游离脂肪酸分配到肝脏 (脂肪溢出) 和脂肪细胞因子失衡 (脂联素减少和/或促炎细胞因子增加) 介导的。游离脂肪酸和脂肪细胞因子都激活炎症途径,包括蛋白激酶C,转录因子核因子kappaB和c 6月N端激酶1,从而可以加速肝脂肪变性向非酒精性脂肪性肝炎和肝硬化的进展。质子磁共振波谱已使量化HCL浓度并在临床环境中检测到这些浓度的微小变化成为可能。中度低热量,减脂饮食可使HCL水平降低约40-80%,同时减少多达8% 的体重。噻唑烷二酮类药物 (例如吡格列酮和罗格列酮) 的治疗通过调节2型糖尿病中脂肪组织的胰岛素敏感性和内分泌功能,将HCL水平降低30-50%。二甲双胍改善肝胰岛素作用而不影响HCL水平,而胰岛素输注67小时可使HCL水平增加约18%; 此外,在胰岛素治疗的2型糖尿病中,HCL水平与胰岛素剂量呈正相关。总之,肝脏脂肪是代谢通量和炎症过程的关键决定因素,因此是胰岛素抵抗和2型糖尿病的重要治疗目标。
  • 【垂体切除术前后垂体依赖性高肾上腺皮质激素,皮质醇,α-黑素细胞刺激激素和生长激素的血浆谱。】 复制标题 收藏 收藏
    DOI:10.1677/joe.1.06782 复制DOI
    作者列表:Hanson JM,Kooistra HS,Mol JA,Teske E,Meij BP
    BACKGROUND & AIMS: :The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.
    背景与目标: : 在17只垂体切除术前后,研究了促肾上腺皮质激素 (ACTH),皮质醇,α-黑素细胞刺激激素 (alpha-MSH) 和GH的6小时血浆谱。该研究的目的是研究PDH术后激素特征与复发之间的关系。荷尔蒙以脉动的方式分泌。PDH病例的基础血浆皮质醇浓度和皮质醇曲线下面积 (AUC) 显着高于八个对照。在PDH病例和对照组之间,ACTH和 α-MSH的血浆特征没有显着差异。在PDH病例中,脉冲分泌的GH比对照组少,但差异不显着。PDH组患者垂体切除术后,基础血浆皮质醇浓度,ACTH和皮质醇的AUC以及ACTH和皮质醇的脉冲频率显着降低。垂体切除术后,PDH病例的基础血浆ACTH和 α-MSH的血浆浓度,α-MSH的AUC以及血浆GH谱的特征保持不变。垂体切除术后未观察到 α-MSH脉冲。垂体切除术后,ACTH和皮质醇脉冲之间的共存显着减少。ACTH的术后脉搏频率是垂体切除术后PDH复发的唯一特征,具有预测价值。这项研究的结果表明,患有PDH的狗以脉动方式分泌ACTH,皮质醇,α-MSH和GH。垂体切除术有效地减少了ACTH和皮质醇的分泌。垂体切除术后ACTH脉冲的存在是肾上腺皮质亢进症复发的危险因素。
  • 4 bcl-2 expression in pilomatricoma. 复制标题 收藏 收藏

    【bcl-2在毛瘤中的表达。】 复制标题 收藏 收藏
    DOI:10.1097/00000372-199706000-00009 复制DOI
    作者列表:Farrier S,Morgan M
    BACKGROUND & AIMS: Pilomatricoma is a distinctive tumor characterized by a dual population of proliferating basophilic cells and diagnostic shadow cells, believed to arise from the hair matrix. The normal hair matrix undergoes defined cycles of growth (anagen), regression (catagen), and resting (telogen) that are regulated by programmed cell death (apoptosis). bcl-2 is a proto-oncogene that helps to suppress apoptosis in both benign and malignant tumors. In addition, both apoptosis and bel-2 are critical factors in normal hair follicle development. In order to clarify the role of bcl-1, we used immunohistochemical means to study 10 cases of histologically proven pilomatricoma for bcl-2 expression. The study design included both positive and negative controls. All of the pilomatricomas in our series were strongly decorated by bcl-2 immunostaining. Based on our findings of increased bcl-2 staining, we concluded that the faulty suppression of apoptosis contributes to the pathogenesis of pilomatricoma.

    背景与目标: 毛瘤瘤是一种独特的肿瘤,其特征是增殖的嗜碱性细胞和诊断阴影细胞的双重群体,据信它们是由毛发基质引起的。正常的头发基质经历了由程序性细胞死亡 (凋亡) 调节的生长 (anagen),回归 (catagen) 和静息 (telogen) 周期。bcl-2是一种原癌基因,有助于抑制良性和恶性肿瘤的细胞凋亡。此外,细胞凋亡和bel-2都是正常毛囊发育的关键因素。为了阐明bcl-1的作用,我们使用免疫组织化学手段研究了10例经组织学证实的毛瘤bcl-2表达。研究设计包括阳性和阴性对照。我们系列中的所有绒毛瘤均通过bcl-2免疫染色强烈修饰。根据我们对bcl-2染色增加的发现,我们得出结论,对细胞凋亡的错误抑制有助于毛瘤的发病机理。
  • 【interleukin-1对大鼠培养的Ito细胞的放松作用。】 复制标题 收藏 收藏
    DOI:10.1002/hep.510250618 复制DOI
    作者列表:Sakamoto M,Ueno T,Sugawara H,Torimura T,Tsuji R,Sujaku K,Sata M,Tanikawa K
    BACKGROUND & AIMS: Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

    背景与目标: Interleukin-1beta (IL-1beta) 与肝脏疾病密切相关。IL-1beta在血管平滑肌细胞中产生一氧化氮 (NO),并通过环鸟苷3 ',5'-单磷酸 (cGMP) 松弛血管平滑肌。在这项研究中,我们评估了IL-1beta对培养的Ito细胞的松弛作用。从雄性Wistar大鼠的肝脏中分离Ito细胞,并培养24小时。使用共聚焦激光显微镜检查诱导型一氧化氮合酶 (iNOS) 和cGMP的免疫定位以及cGMP的荧光强度。Ito细胞用0、200和1,000 pmol/L IL-1beta处理,12小时后测定细胞内cGMP浓度。此外,在12小时内观察到用200和1,000 pmol/L IL-1beta处理和不用IL-1beta处理的Ito细胞,并比较在添加IL-1beta前后相同Ito细胞的面积。接下来,通过IL-1beta处理检查了N(G)-单甲基-L-精氨酸 (L-NMMA) 和S-亚硝基-N-乙酰基-DL-青霉胺 (SNAP) 对Ito细胞松弛的影响。在Ito细胞中,观察到iNOS的免疫荧光,加入IL-1beta后cGMP的荧光强度增加。加入IL-1beta后,细胞内cGMP浓度呈剂量依赖性增加。与未处理组相比,IL-1beta-treated组的细胞面积显着增加。IL-1beta处理对Ito细胞的松弛以剂量依赖性方式被l-nmma抑制,但被SNAP增强。这些结果表明,IL-1beta在培养的Ito细胞中产生NO,并通过cGMP使细胞松弛。
  • 【躁狂抑郁症与GABRbeta-1基因高度多态性标记之间的遗传关联研究。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1096-8628(19970531)74:3<342::aid-ajm 复制DOI
    作者列表:Puertollano R,Visedo G,Zapata C,Fernández-Piqueras J
    BACKGROUND & AIMS: We report on an association study between a tetranucleotide repeat polymorphism in the GABR beta1 gene and manic-depressive illness in a Spanish population. This gene may be an important candidate for bipolar affective disorders since severe GABergic alterations have been described in patients. Although our results do not reveal a clear evidence for association between manic-depressive illness and GABR beta1, we have found significant differences between patients and controls in the female subpopulation.

    背景与目标: 我们报告了一项西班牙人群中GABR beta1基因的四核苷酸重复多态性与躁狂抑郁症之间的关联研究。该基因可能是双相情感障碍的重要候选者,因为已经在患者中描述了严重的GABergic改变。尽管我们的结果并未揭示出躁狂抑郁症与GABR beta1之间存在关联的明确证据,但我们发现女性亚群的患者与对照组之间存在显着差异。
  • 【鸡GATA-2和GATA-3的N端指是独立的序列特异性DNA结合结构域。】 复制标题 收藏 收藏
    DOI:10.1093/emboj/16.10.2874 复制DOI
    作者列表:Pedone PV,Omichinski JG,Nony P,Trainor C,Gronenborn AM,Clore GM,Felsenfeld G
    BACKGROUND & AIMS: The GATA family of vertebrate DNA binding regulatory proteins are expressed in diverse tissues and at different times of development. However, the DNA binding regions of these proteins possess considerable homology and recognize a rather similar range of DNA sequence motifs. DNA binding is mediated through two domains, each containing a zinc finger. Previous results have led to the conclusion that although in some cases the N-terminal finger can contribute to specificity and strength of binding, it does not bind independently, whereas the C-terminal finger is both necessary and sufficient for binding. Here we show that although this is true for the N-terminal finger of GATA-1, those of GATA-2 and GATA-3 are capable of strong independent binding with a preference for the motif GATC. Binding requires the presence of two basic regions located on either side of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal finger probably accounts for its inability to bind. The combination of a single finger and two basic regions is a new variant of a motif that has been previously found in the binding domains of other finger proteins. Our results suggest that the DNA binding properties of the N-terminal finger may help distinguish GATA-2 and GATA-3 from GATA-1 and the other GATA family members in their selective regulatory roles in vivo.

    背景与目标: 脊椎动物DNA结合调节蛋白的GATA家族在不同的组织和发育的不同时间表达。但是,这些蛋白质的DNA结合区域具有相当大的同源性,并且可以识别相当相似范围的DNA序列基序。DNA结合通过两个结构域介导,每个结构域都包含一个锌指。先前的结果得出的结论是,尽管在某些情况下,N末端手指可以促进特异性和结合强度,但它不会独立结合,而C末端手指对于结合既必要又足够。在这里,我们表明,尽管对于GATA-1的N末端手指是正确的,但GATA-2和GATA-3的手指能够强烈独立结合,并且偏爱基序GATC。结合需要存在位于N末端手指两侧的两个基本区域。在GATA-1的N末端手指附近没有这些手指之一可能是其无法结合的原因。单个手指和两个基本区域的组合是基序的新变体,以前已在其他手指蛋白的结合域中发现。我们的结果表明,N末端手指的DNA结合特性可能有助于将GATA-2和GATA-3与GATA-1和其他GATA家族成员在体内的选择性调节作用区分开。
  • 【与DRA X2-box结合的NF-X2是激活蛋白1。c-6月的表达克隆】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Andersson G,Peterlin BM
    BACKGROUND & AIMS: :Human class II MHC Ag are a family of cell surface glycoproteins. Their constitutive expression is limited to B lymphocytes and thymic epithelial cells. In many other cells their expression can be induced by IFN-gamma. Conserved upstream promoter sequences regulate this tissue-specific expression of class II genes. In the DRA promoter, one of these cis-acting regulatory motifs is the X2-box to which nuclear factor X2 (NF-X2) binds. Here, we present the isolation and characterization of the full-length cDNA clone encoding NF-X2. This cDNA clone was isolated by expression cDNA cloning, and encodes the human c-Jun protein, which together with c-Fos forms the heterodimeric activator protein-1 transcription complex. Whereas c-Fos/c-Jun heterodimers do not exist in B cells, they form and bind to the X2-box in class II nonexpressing cells. Thus, c-Fos/c-Jun heterodimers might contribute to the repression of DRA gene expression.
    背景与目标: : 人类II类MHC Ag是细胞表面糖蛋白家族。它们的组成型表达仅限于B淋巴细胞和胸腺上皮细胞。在许多其他细胞中,它们的表达可以通过IFN-γ 诱导。保守的上游启动子序列调节II类基因的这种组织特异性表达。在DRA启动子中,这些顺式作用调节基序之一是核因子X2 (NF-X2) 结合的X2-box。在这里,我们介绍了编码NF-X2的全长cDNA克隆隔离和表征。通过表达cDNA克隆分离该cDNA克隆,并编码人c 6月蛋白,该蛋白与c-Fos一起形成异二聚体激活蛋白1转录复合物。尽管b细胞中不存在c-Fos/c-6月异二聚体,但它们在II类非表达细胞中形成并结合X2-box。因此,c-Fos/c-6月异二聚体可能有助于抑制DRA基因表达。
  • 【使用可生物降解的聚L-丙交酯支架进行髂吻合支架置入术: 1周和6周后的初步研究。】 复制标题 收藏 收藏
    DOI:10.1583/05-1726MR.1 复制DOI
    作者列表:Bünger CM,Grabow N,Sternberg K,Ketner L,Kröger C,Lorenzen B,Hauenstein K,Schmitz KP,Kreutzer HJ,Lootz D,Ince H,Nienaber CA,Klar E,Schareck W
    BACKGROUND & AIMS: PURPOSE:To assess the technical feasibility, thrombogenicity, and biocompatibility of a new biodegradable poly-L-lactic acid (PLLA) anastomotic stent. METHODS:A polytetrafluoroethylene bifurcated graft was implanted in 17 pigs through a midline abdominal incision. After transverse graft incision, 17 316L stainless steel stents and 17 PLLA stents were randomly implanted at both iliac anastomotic sites and deployed with a 6-mm balloon under direct vision without angiography. Intended follow-up was 1 week in 6 pigs receiving oral acetylsalicylic acid (ASA) and in 7 pigs receiving ASA/clopidogrel; 4 pigs receiving ASA/clopidogrel were followed for 6 weeks. At the end of the study, the segments containing the stents were surgically explanted and processed for histology to measure the mean luminal diameter, intimal thickness, and the vascular injury and inflammation scores. RESULTS:Initial technical success of stent placement was achieved in all animals without rupture of the suture. Two pigs died (unrelated to the stent) at 3 days after operation (1 in groups A and B). At 1 week, all PLLA stents showed thrombotic occlusion with the use of ASA alone. In contrast, all PLLA stents remained patent with concurrent administration of ASA/clopidogrel. All metal stents were patent regardless of the antiplatelet regimen. The mean luminal diameter of patent PLLA stents (4.13+/-0.17 mm) was comparable to metal stents (4.27+/-0.35 mm, p=0.78) at 1 week, but significantly diminished at 6 weeks (3.21+/-0.44 versus 4.19+/-0.18 mm, p=0.005). Histological analysis showed no signs of excessive recoil. PLLA stents induced a higher inflammation score (1.79+/-0.56) and more intimal hyperplasia (0.34+/-0.11 mm) compared to metal stents [1.27+/-0.44 mm (p<0.001) and 0.18+/-0.04 mm (p=0.006), respectively] at 6 weeks. Vascular injury was comparable between PLLA and metal stents. CONCLUSION:Biodegradable PLLA stents showed higher thrombogenicity and reduced patency compared to metal stents during early follow-up. Although ASA and clopidogrel prevented thrombotic occlusion, the increased inflammatory response and neointima formation remain major concerns of PLLA stents. A solution to this problem might be the incorporation of anti-inflammatory drugs into the PLLA stent.
    背景与目标:
  • 【T(2) 加权的显微mri和视觉系统的诱发电位在低髓转基因小鼠的发育过程中测量。】 复制标题 收藏 收藏
    DOI:10.1007/s11064-006-9121-z 复制DOI
    作者列表:Martin M,Reyes SD,Hiltner TD,Givogri MI,Tyszka JM,Fisher R,Campagnoni AT,Fraser SE,Jacobs RE,Readhead C
    BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.
    背景与目标: : 我们的目标是使用非侵入性高分辨率 (117x70 microm) 磁共振 (microMRI) 和视觉系统诱发电位 (VEP) 技术,跟踪畸形疾病的过程,然后在转基因小鼠中进行部分恢复。我们使用了JOE (用于J37 golli过表达) 转基因小鼠,该小鼠经过工程改造以过表达golli J37,Golli-mbp基因复合物的产物,特别是在少突胶质细胞中。从21天到75天大,在11.7 T扫描仪上使用非侵入性体内vep和3D T2-weighted显微mri跟踪了JOE transgenics及其未受影响的兄弟姐妹,我们认为这是同类研究中的首次纵向研究。microMRI数据表明,在髓鞘形成峰值期间 (21-42天),明显的整体髓鞘减少,与对照组相比,JOE小鼠在以后的年龄 (>60天) 得到了部分纠正。这些显微mri数据与 [Campagnoni在 (1995) “髓鞘形成的分子生物学” 处有很好的相关性。见: Ransom B,Kettenmann H (eds) 神经胶质-一篇论文。牛津大学出版社,伦敦,第555-570页] 髓磷脂染色,[Campagnoni AT,macklin WB (1988) 髓鞘蛋白基因表达的细胞和分子方面。Mol Neurobiol 2:41-89] 在髓鞘形成的高峰期短暂的意图震颤,在以后的年龄减弱,并且 [Lees MB,Brostoff SW (1984) 蛋白在髓鞘中: morell (ed) 髓鞘。纽约和伦敦的Plenum出版社,pp 197-224] VEPs,所有这些都表明乔小鼠中枢神经系统髓鞘发育和持续的低髓鞘作用显着延迟。总体而言,这些非侵入性技术能够在空间上解决正常发育和发育延迟的小鼠大脑中髓鞘形成的增加。
  • 【图30: 一种新的HIV-1感染和复制抑制剂。】 复制标题 收藏 收藏
    DOI:10.1016/0014-5793(90)80438-o 复制DOI
    作者列表:Lee-Huang S,Huang PL,Nara PL,Chen HC,Kung HF,Huang P,Huang HI,Huang PL
    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。
  • 【山羊 α-乳白蛋白中单个Trp残基的荧光贡献。】 复制标题 收藏 收藏
    DOI:10.1016/j.bbapap.2006.07.011 复制DOI
    作者列表:Vanhooren A,Illyes E,Majer Z,Hanssens I
    BACKGROUND & AIMS: :Goat alpha-lactalbumin (GLA) contains four tryptophan (Trp) residues. In order to obtain information on the fluorescence contribution of the individual Trp residues in native GLA, we recorded the fluorescence spectra of four GLA mutants, W26F, W60F, W104F, and W118F, in each of which a single Trp residue was replaced with phenylalanine (Phe). Comparison of the fluorescence spectra of the four mutants with that of wild-type GLA indicated that, in native GLA, three Trp residues (Trp60, Trp104, and Trp118) are strongly quenched and account for the partial indirect quenching of Trp26. As a consequence, the fluorescence of wild-type GLA and of the mutants W60F, W104F, and W118F mainly results from Trp26. An inspection of the crystal structure indicated that, in addition to the disulfide bonds that are in direct contact with the indole groups of Trp60 and Trp118, backbone peptide bonds that are in direct contact with the indole groups of Trp60, Trp104, and Trp118, contribute to the direct quenching effects. Interestingly, the lack of direct quenching of Trp26 explains why the cleavage of disulfide bonds by UV light is mediated more by the highly fluorescent Trp26 than by the less fluorescent Trp104 and Trp118.
    背景与目标: : 山羊 α-乳白蛋白 (GLA) 含有四个色氨酸 (Trp) 残基。为了获得有关天然GLA中单个Trp残基的荧光贡献的信息,我们记录了四个GLA突变体W26F,W60F,W104F和W118F的荧光光谱,其中每个单个Trp残基被替换为苯丙氨酸 (Phe)。将四个突变体的荧光光谱与野生型GLA的荧光光谱进行比较表明,在天然GLA中,三个Trp残基 (Trp60,Trp104和Trp118) 被强烈淬灭,并解释了trp26的部分间接猝灭。因此,野生型GLA和突变体W60F,W104F和W118F的荧光主要来自trp26。对晶体结构的检查表明,除了与Trp60和Trp118的吲哚基团直接接触的二硫键外,与Trp60,Trp104和Trp118的吲哚基团直接接触的骨架肽键有助于直接猝灭作用。有趣的是,缺乏Trp26的直接猝灭解释了为什么高荧光的Trp26比低荧光的Trp104和trp118更多地介导紫外光对二硫键的裂解。
  • 【[分子生物学为日常医学病毒学服务。2.在病毒学诊断中的应用]。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Wattré P
    BACKGROUND & AIMS: :Molecular biology techniques are applied for the diagnosis of meningoencephalitis due to herpesviruses, enteroviruses or polyomaviruses, for the diagnosis of human cytomegalovirus, human parvovirus B19, varicella-zoster virus and rubella virus infections occurring during pregnancy, for the diagnosis and the management of retrovirus infections (HIV and HTLV) and of hepatitis (HBV and HCV), for papillomavirus typing and to detect a link between virus and clinical manifestations (cardiomyopathy or insulinodependent diabetes with coxsackievirus B: Kaposi's sarcoma with HHV 8) or to investigate an environmental contamination with viruses. These new molecular markers which are both qualitative and quantitative represent an important advance in the field of viral diagnosis research, in the monitoring of viral load during the course of infection, in the therapy control of viral disease and in the epidemiology of virus spread. Standardization and automatization are obtained using available commercial reagents and kits.
    背景与目标: : 分子生物学技术用于诊断由疱疹病毒,肠病毒或多瘤病毒引起的脑膜脑炎,用于诊断人巨细胞病毒病毒,人细小病毒B19,水痘病毒病毒和怀孕期间发生的风疹病毒病毒,用于诊断和管理复古病毒感染 (HIV和HTLV) 和肝炎 (HBV和HCV),乳头瘤病毒分型,并检测病毒与临床表现 (心肌病或胰岛素依赖型糖尿病与柯萨奇病毒B: 卡波西氏肉瘤与HHV 8) 或调查病毒es的环境污染。这些定性和定量的新分子标记物代表了病毒诊断研究领域,感染过程中病毒载量的监测,病毒性疾病的治疗控制以及病毒传播流行病学领域的重要进展。使用可用的商业试剂和试剂盒可获得标准化和自动化。
  • 【根据哌唑嗪的亲和力,人类良性前列腺肥大组织中的 α-1肾上腺素受体亚型 (高,低)。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0045(19970601)31:4<216::aid-pro 复制DOI
    作者列表:Takeda M,Hatano A,Komeyama T,Koizumi T,Mizusawa T,Kanai T,Tomita Y,Maruyama K,Nagatomo T
    BACKGROUND & AIMS: BACKGROUND:A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue. METHODS:Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies. RESULTS:(1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes. CONCLUSIONS:Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.
    背景与目标:
  • 【产气荚膜梭菌的 α 毒素不是鸡坏死性肠炎的必需毒力因子。】 复制标题 收藏 收藏
    DOI:10.1128/IAI.00806-06 复制DOI
    作者列表:Keyburn AL,Sheedy SA,Ford ME,Williamson MM,Awad MM,Rood JI,Moore RJ
    BACKGROUND & AIMS: :The Clostridium perfringens alpha-toxin has previously been implicated as the major virulence factor in necrotic enteritis in chickens, although definitive proof has not been reported. In this study an alpha-toxin mutant was constructed in a virulent chicken isolate and shown to retain full virulence in a chicken disease model. These results demonstrated that alpha-toxin is not an essential virulence factor in the pathogenesis of necrotic enteritis in chickens.
    背景与目标: : 尽管尚未报道明确的证据,但以前曾将产气荚膜梭菌 α 毒素作为鸡坏死性肠炎的主要毒力因子。在这项研究中,在强毒鸡分离株中构建了一个 α 毒素突变体,并显示在鸡疾病模型中保留了完全的毒力。这些结果表明,在鸡坏死性肠炎的发病机理中,α-毒素不是必需的毒力因子。

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