• 【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。
  • 【谷胱甘肽缺乏症遗传模型中小脑颗粒神经元中软骨藻酸的神经毒性。】 复制标题 收藏 收藏
    DOI:10.1124/mol.106.027748 复制DOI
    作者列表:Giordano G,White CC,McConnachie LA,Fernandez C,Kavanagh TJ,Costa LG
    BACKGROUND & AIMS: :This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm). Glutamate-cysteine ligase (Glc) catalyzes the first and rate-limiting step in glutathione (GSH) biosynthesis. CGNs from Gclm (-/-) mice have very low levels of GSH and are 10-fold more sensitive to DomA-induced toxicity than CGNs from Gclm (+/+) mice. GSH ethyl ester decreased, whereas the Gcl inhibitor buthionine sulfoximine increased DomA toxicity. Antagonists of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors and of N-methyl-D-aspartate (NMDA) receptors blocked DomA toxicity, and NMDA receptors were activated by DomA-induced l-glutamate release. The differential susceptibility of CGNs to DomA toxicity was not due to a differential expression of ionotropic glutamate receptors, as evidenced by similar calcium responses and L-glutamate release in the two genotypes. A calcium chelator and several antioxidants antagonized DomA-induced toxicity. DomA caused a rapid decrease in cellular GSH, which preceded toxicity, and the decrease was primarily due to DomA-induced GSH efflux. DomA also caused an increase in oxidative stress as indicated by increases in reactive oxygen species and lipid peroxidation, which was subsequent to GSH efflux. Astrocytes from both genotypes were resistant to DomA toxicity and presented a diminished calcium response to DomA and a lack of DomA-induced L-glutamate release. Because polymorphisms in the GCLM gene in humans are associated with low GSH levels, such individuals, as well as others with genetic conditions or environmental exposures that lead to GSH deficiency, may be more susceptible to DomA-induced neurotoxicity.
    背景与目标: : 这项研究通过使用缺乏谷氨酸-半胱氨酸连接酶修饰亚基 (Gclm) 的小鼠的小脑颗粒神经元 (CGNs),研究了细胞抗氧化防御机制在调节软骨藻酸 (DomA) 神经毒性中的作用。谷氨酸-半胱氨酸连接酶 (Glc) 催化谷胱甘肽 (GSH) 生物合成中的第一个和限速步骤。来自Gclm (-/-) 小鼠的CGNs的GSH水平非常低,并且对DomA诱导的毒性的敏感性比来自Gclm (/) 小鼠的CGNs高10倍。GSH乙酯降低,而Gcl抑制剂丁硫氨酸亚砜肟增加了DomA毒性。alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic/海藻酸盐受体和N-甲基-D-天冬氨酸 (NMDA) 受体的拮抗剂阻断了DomA毒性,并且NMDA受体被DomA诱导的l-谷氨酸释放激活。CGNs对DomA毒性的敏感性差异不是由于离子型谷氨酸受体的表达差异所致,这在两种基因型中钙反应和L-谷氨酸释放相似。钙螯合剂和几种抗氧化剂拮抗DomA诱导的毒性。DomA导致细胞GSH迅速下降,这先于毒性,并且下降主要是由于DomA诱导的GSH外排。DomA还引起了氧化应激的增加,如活性氧种类和脂质过氧化的增加所表明的,这是在GSH外排之后。两种基因型的星形胶质细胞均对DomA毒性具有抗性,并且对DomA的钙反应减弱,并且缺乏DomA诱导的L-谷氨酸释放。由于人类GCLM基因的多态性与低GSH水平相关,因此此类个体以及具有导致GSH缺乏的遗传条件或环境暴露的其他个体可能更容易受到DomA诱导的神经毒性的影响。
  • 【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。
  • 【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:
  • 【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。
  • 【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。
  • 【巴巴多斯黑人中的严重原发性HIV-1感染。】 复制标题 收藏 收藏
    DOI:10.1258/0956462971920325 复制DOI
    作者列表:Hudson CP,Levett PN,Edwards CN,Moosai R,Roach TC
    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:
  • 【CD5 (Ly-1) 阴性的常规脾b细胞对CBA和BW小鼠的菠萝蛋白酶斑块形成细胞反应做出了重大贡献。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Andrew EM,Annis W,Kahan M,Maini RN
    BACKGROUND & AIMS: :CD5 (Ly-1) B cells are a minor subpopulation in mouse spleen and are thought to be responsible for the production of natural autoantibodies to bromelain-treated autologous erythrocytes (Br-RBC). Here it is shown that substantial numbers of conventional, CD5-negative, splenic B cells also secrete these antibodies in CBA and (NZB x NZW)F1 mice, whereas in NZB and BALB/c mice they are all produced by the CD5 B-cell population. However, stimulation with bacterial lipopolysaccharide in vivo preferentially activates the CD5 B-cell group to anti-Br-RBC antibody secretion.
    背景与目标: : CD5 (Ly-1) b细胞是小鼠脾脏中的次要亚群,被认为负责产生针对菠萝蛋白酶处理的自体红细胞 (br-rbc) 的天然自身抗体。这里显示大量的常规CD5-negative脾b细胞也在CBA和 (NZB x NZW)F1小鼠中分泌这些抗体,而在NZB和BALB/c小鼠中,它们都是由CD5 b细胞群体产生的。然而,体内用细菌脂多糖刺激优先激活CD5 b细胞组,使其分泌抗br-rbc抗体。
  • 【雌激素过量引起的缺乏1型5α-还原酶的小鼠的胎儿死亡。】 复制标题 收藏 收藏
    DOI:10.1210/mend.11.7.9933 复制DOI
    作者列表:Mahendroo MS,Cala KM,Landrum DP,Russell DW
    BACKGROUND & AIMS: :Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5alpha-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5alpha-reduce androgens leads to their conversion to estrogens, which in turn causes fetal death in midgestation. These findings indicate that the 5alpha-reduction of androgens in female animals plays a crucial role in guarding against estrogen toxicity during pregnancy.
    背景与目标: : 缺乏类固醇5α-还原酶1型的雌性小鼠的产仔数减少。纯合缺陷雌性的平均产仔为2.7幼仔,而野生型对照为8.0幼仔。在突变动物中,卵子发生,受精,植入和胎盘形态似乎正常。胎儿损失发生在妊娠10.75和11.0之间,与妊娠中期胎盘雄激素产生激增和野生型小鼠蜕膜中5α-还原酶1型表达的诱导相称。在妊娠第9天,雄烯二酮和睾丸激素的血浆水平高2至3倍,在整个妊娠早期和中期,敲除小鼠的雌二醇水平长期升高2至3倍。施用雌激素受体拮抗剂或芳香化酶抑制剂可逆转突变小鼠的高胎儿死亡率,而雌二醇处理野生型妊娠小鼠会导致胎儿浪费。结果表明,在缺陷小鼠中,未能减少5α-雄激素会导致其转化为雌激素,进而导致妊娠中期胎儿死亡。这些发现表明,雌性动物中雄激素的5α 减少在预防怀孕期间的雌激素毒性中起着至关重要的作用。
  • 【在正常和脱水大鼠中,μ 阿片受体是否参与控制垂体endothelin-1释放?】 复制标题 收藏 收藏
    DOI:10.1016/s0167-0115(97)02134-4 复制DOI
    作者列表:Płonowski A,Szymańska-Debińska T,Radzikowska M,Baranowska B,Woźniewicz B
    BACKGROUND & AIMS: UNLABELLED:The objective of the present study was to investigate whether the endogenous opioids are involved in the control of endothelin-1 release from the pituitary gland. To test this hypothesis we have measured the peripheral plasma concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in the pituitary in response to opioid receptors blockade in euhydrated and 24 h water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body wt.) were given i.v. in both groups. Trunk blood was collected to determine hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the whole pituitary glands was performed by colloidal gold labeling. The quantitative analysis of irET-1 was carried out under a light microscope using a computerized image analyzer (MultiScan). RESULTS:(1) Twenty-four-hour dehydration resulted in marked increase of peripheral concentration of ET-1. Naltrexone injection induced a significant elevation of ET-1 plasma concentration in both, dehydrated and control animals. (2) The content of irET-1 in anterior and intermediate lobes of the pituitary in dehydrated rats was markedly higher than in control group. (3) Naltrexone injection caused a rapid and significant reduction irET-1 within the anterior, intermediate and posterior lobes in dehydrated and control animals. CONCLUSIONS:(1) An elevation of irET-1 in the pituitary gland and peripheral circulation in dehydrated animals may play a role in maintaining of water-electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release from the pituitary in normal and dehydrated animals.
    背景与目标:
  • 【前沿: 人STAT5b缺乏症中CD4 + CD25 (高) T细胞的积累和调节功能降低。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.177.5.2770 复制DOI
    作者列表:Cohen AC,Nadeau KC,Tu W,Hwa V,Dionis K,Bezrodnik L,Teper A,Gaillard M,Heinrich J,Krensky AM,Rosenfeld RG,Lewis DB
    BACKGROUND & AIMS: :We show that STAT5b is important for the in vivo accumulation of CD4+ CD25(high) T cells with regulatory cell function. A patient homozygous for a missense A630P STAT5b mutation displayed immune dysregulation and decreased numbers of CD4+ CD25(high) T cells. STAT5b(A630P/A630P) CD4+ CD25(high) T cells had low expression of forkhead box P3 and an impaired ability to suppress the proliferation of or to kill CD4+ CD25- T cells. Expression of CD25, a component of the high-affinity IL-2R, was also reduced in response to IL-2 or after in vitro propagation. The impact of the STAT5b mutation was selective in that IL-2-mediated up-regulation of the common gamma-chain cytokine receptor and perforin, and activation-induced expressions of CD154 and IFN-gamma were normal. These results indicate that STAT5b propagates an important IL-2-mediated signal for the in vivo accumulation of functional regulatory T cells.
    背景与目标: : 我们显示STAT5b对于具有调节细胞功能的CD4 CD25 (高) T细胞的体内积累很重要。一名因错义A630P STAT5b突变而纯合的患者表现出免疫失调和CD4 CD25 (高) T细胞数量减少。STAT5b(A630P/A630P) CD4 CD25 (高) T细胞的叉头盒P3表达低,抑制或杀死CD4 cd25-t细胞的增殖能力受损。高亲和力IL-2R的组分CD25的表达也在响应IL-2或体外繁殖后降低。STAT5b突变的影响是选择性的,因为IL-2-mediated常见的 γ 链细胞因子受体和穿孔素的上调,并且激活诱导的CD154和IFN-γ 的表达正常。这些结果表明STAT5b传播了功能性调节性T细胞在体内积累的重要IL-2-mediated信号。
  • 【口服多糖凝胶包衣微丸的研制1.物理机械性能。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2006.07.004 复制DOI
    作者列表:Sriamornsak P,Burton MA,Kennedy RA
    BACKGROUND & AIMS: :Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.
    背景与目标: : 将含有茶碱,醋酸钙和微晶纤维素的球形颗粒挤出并球形化,然后通过界面络合用六种不同的果胶或藻酸盐包被。这项研究的目的是发现涂层对物理机械性能的影响,这对于确定颗粒作为持续释放系统的效用至关重要。在核心颗粒周围形成不溶性,光滑且均匀厚的钙多糖涂层。设计了析因实验,以研究颗粒大小,多糖类型和浓度对包封效率,机械性能和其他物理特性的影响。通过扫描电子显微镜观察到包被的颗粒,根据所用的特定多糖,发现干涂层的厚度为30-80微米。颗粒的大小,多糖的类型和浓度影响包衣颗粒中茶碱的产量。尽管通过施加任何凝胶涂层可以改善颗粒的机械性能,但使用具有高含量古罗糖醛酸的藻酸盐或酰胺化的果胶涂层可提供最佳结果。这可能是因为这两者都具有在凝胶涂层内形成非常稳定的交联的巨大潜力。

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