BACKGROUND & AIMS: :Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration and mRNA expression of endothelial lipase (EL) and hormone-sensitive lipase (HSL) were increased in placentas from women with diabetes. The differences were more pronounced in women with diabetes and suboptimal metabolic control than in women with diabetes and good metabolic control. Placental mRNA expression of lipoprotein lipase and lysosomal lipase were similar in women with diabetes and the control group. Immunohistochemistry showed EL protein in syncytiotrophoblasts facing the maternal blood and endothelial cells facing the fetal blood in placentas from both normal women and women with diabetes. These results suggest that maternal type 1 diabetes is associated with TG accumulation and increased EL and HSL gene expression in placenta and that optimal metabolic control reduces these effects.

背景与目标： 孕产妇糖尿病会导致胎儿巨大儿，并在后代成年后增加肥胖，糖尿病和心血管疾病的风险。尽管可能涉及胎盘脂质转运的增加，但母体1型糖尿病对胎盘脂质转运分子机制的影响尚不清楚。为了检查母体1型糖尿病是否影响胎盘脂质代谢，我们测量了1型糖尿病女性（n = 27）和对照组（n = 21）的胎盘中脂质和脂肪酶编码基因的mRNA表达。糖尿病妇女胎盘中胎盘甘油三酸酯（TG）浓度和内皮脂肪酶（EL）和激素敏感性脂肪酶（HSL）的mRNA表达增加。糖尿病和代谢控制欠佳的女性比糖尿病和代谢控制良好的女性更明显。糖尿病女性和对照组胎盘脂蛋白脂肪酶和溶酶体脂肪酶的mRNA表达相似。免疫组织化学显示，正常女性和糖尿病女性的胎盘中，面向孕妇血液的合体滋养层细胞和面向胎儿血液的内皮细胞中的EL蛋白。这些结果表明，孕妇1型糖尿病与TG蓄积和胎盘中EL和HSL基因表达的增加有关，最佳的代谢控制可降低这些影响。

BACKGROUND & AIMS: Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

背景与目标： 白细胞介素-1（IL-1 alpha）在多种良性细胞类型中以及某些但不是全部恶性细胞系中诱导细胞运动。这项研究的特点是表达I型和II型IL-1受体的侵略性人黑素瘤细胞系的IL-1α诱导的运动。我们测试了包括针对I型和II型IL-1受体的功能阻断性单抗的单克隆抗体对黑素瘤细胞运动性的影响，以确定哪个受体参与了IL-1α诱导的黑素瘤细胞运动性的信号转导。 IL-1α使用改良的Boyden室测定法以剂量依赖性方式显着增加MM-RU黑色素瘤细胞迁移，其浓度比明显抑制细胞生长的浓度低10至100倍。计算机辅助的延时图像分析表明，通过中和针对IL-1α的抗体，可以以剂量依赖性的方式抑制运动性。针对I型或II型IL-1受体的功能阻断性单克隆抗体显示出对细胞因子诱导的细胞迁移增强的显着抑制作用。当两种抗IL-1受体抗体一起添加时，运动反应完全被阻断至对照水平。数据合计表明，IL-1α诱导的MM-RU黑色素瘤细胞的运动是通过I型和II型IL-1受体介导的。通过中和IL-1α或阻断任何一个IL-1受体或两个IL-1受体来显着抑制运动性，这表明在黑素瘤细胞迁移的诱导中整合了IL-1诱导的信号。

BACKGROUND & AIMS: :Matrix assembly and homeostasis in collagen-rich tissues are mediated by interactions with proteoglycans (PGs) substituted with sulfated glycosaminoglycans (GAGs). The major GAG in cornea is keratan sulfate (KS), which is N-linked to one of three PG core proteins. To ascertain the importance of the carbohydrate chain sulfation step in KS functionality, we generated a strain of mice with a targeted gene deletion in Chst5, which encodes an N-acetylglucosamine-6-O-sulfotransferase that is integral to the sulfation of KS chains. Corneas of homozygous mutants were significantly thinner than those of WT or heterozygous mice. They lacked high-sulfated KS, but contained the core protein of the major corneal KSPG, lumican. Histochemically stained KSPGs coassociated with fibrillar collagen in WT corneas, but were not identified in the Chst5-null tissue. Conversely, abnormally large chondroitin sulfate/dermatan sulfate PG complexes were abundant throughout the Chst5-deficient cornea, indicating an alteration of controlled PG production in the mutant cornea. The corneal stroma of the Chst5-null mouse exhibited widespread structural alterations in collagen fibrillar architecture, including decreased interfibrillar spacing and a more spatially disorganized collagen array. The enzymatic sulfation of KS GAG chains is thus identified as a key requirement for PG biosynthesis and collagen matrix organization.

背景与目标： ：胶原蛋白丰富的组织中的基质组装和体内平衡是通过与被硫酸化的糖胺聚糖（GAG）取代的蛋白聚糖（PG）的相互作用而介导的。角膜中的主要GAG是硫酸角质素（KS），它与三种PG核心蛋白之一进行N-连接。为了确定碳水化合物链硫酸化步骤在KS功能中的重要性，我们生成了在Chst5中具有靶向基因缺失的小鼠品系，该菌株编码一个N-乙酰氨基葡糖-6-O-磺基转移酶，该酶是KS链硫酸化所必需的。纯合突变体的角膜明显比野生型或杂合小鼠的角膜薄。他们缺乏高硫酸盐化的KS，但含有主要角膜KSPG的核心蛋白lumican。组织化学染色的KSPG与野生型角膜中的原纤维胶原蛋白相关联，但在Chst5无组织中未发现。相反，在整个Chst5缺陷型角膜中，异常大的硫酸软骨素/硫酸皮肤素PG复合物丰富，表明突变体角膜中受控PG产生的改变。 Chst5-null小鼠的角膜基质在胶原纤维结构中表现出广泛的结构变化，包括减小的纤维间间距和空间上更混乱的胶原阵列。因此，KS GAG链的酶促硫酸化被确定为PG生物合成和胶原基质组织的关键要求。

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： ：本研究的目的是检查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例患者（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加权脑体积的分段灰质（GM）和白质（WM）。我们发现与对照组相比，SCA3的脑桥和s中的灰质减少。在SCA6中，在双侧的半球小叶以及在mis骨中都发现了明显的灰质损失。白质分析显示，SCA3的显着变化，尤其是在脑桥，齿状核（DN）周围的白质和小脑梗的脑桥中，特别是在脑桥中，而在SCA6患者中未发现显着的白质减少。我们的结果表明，在SCA3和SCA6患者中通过磁共振成像（MRI）检测到不同的灰白色和白色物质影响模式，证实了SCA6皮质小脑萎缩的病理学概念。相反，SCA3代表了一种桥脑小脑萎缩的形式，主要影响桥脑核和纤维束。

BACKGROUND & AIMS: :Few details are known about how the human immunodeficiency virus type 1 (HIV-1) genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is investigated in this study. Using immunofluorescence and fluorescence in situ hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1-expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a distinct, cytoplasmic space that corresponds to the microtubule-organizing center (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a result of hnRNP A2 knockdown even during the expression of a provirus harboring mutations in the hnRNP A2-response element (A2RE), the expression of which results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2 expression is required for downstream trafficking of genomic RNA from the MTOC in the cytoplasm. Genomic RNA localization at the MTOC that was both the result of hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein had little effect on pr55Gag synthesis but negatively influenced virus production and infectivity. These data indicate that altered HIV-1 genomic RNA localization modulates viral assembly and that the MTOC serves as a central site to which HIV-1 genomic RNA converges following its exit from the nucleus, with the host protein, hnRNP A2, playing a central role in taking it to and from this site in the cell.

背景与目标： 关于人类免疫缺陷病毒1型（HIV-1）基因组RNA如何在细胞质中运输的信息鲜为人知。该过程的一部分受异质核核糖核蛋白A2（hnRNP A2）的活性控制。这项研究调查了hnRNP A2在HeLa细胞中表达真正的原病毒的过程中的作用。使用免疫荧光和荧光原位杂交技术，我们显示敲低表达HIV-1的细胞中hnRNP A2表达的表达导致HIV-1基因组RNA在与微管组织中心相对应的独特细胞质空间中的快速积累（ MTOC）。即使hnRNP A2反应元件（A2RE）中携带有突变的原病毒表达，RNA仍会通过hnRNP A2敲除而留在细胞核中并积聚在MTOC区。 。我们还证明hnRNP A2表达是从细胞质MTOC下游运输基因组RNA所必需的。基因组RNA在MTOC处的定位既是hnRNP A2敲除的结果，又是与Rab7相互作用的溶酶体蛋白的过表达，对pr55Gag的合成影响很小，但对病毒的产生和感染性产生负面影响。这些数据表明，改变的HIV-1基因组RNA定位可调节病毒装配，MTOC充当HIV-1基因组RNA从细胞核退出后向其汇聚的中心位点，宿主蛋白hnRNP A2发挥着核心作用。将其带入和移出该单元格中的此站点。

BACKGROUND & AIMS: We studied changes in glutamate receptors, expression of immediate early genes, and AP-1 DNA binding activity in the brains of phenobarbital (PB)-dependent and -withdrawn rats to investigate the possible involvement of activation of glutamate receptors in PB withdrawal syndrome. PB-dependent rats were prepared by feeding drug-admixed food for 5 weeks. Autoradiographic analysis showed that binding of [3H(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imin e (MK-801), an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, increased significantly in the cerebral cortices of PB-dependent and 24-h-withdrawn rats. However, [3H]MK-801 binding in the hippocampus and [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and [3H]kainic acid binding in the hippocampus and cerebral cortex were essentially unchanged in both groups. PB withdrawal seizures were followed by increased expression of c-fos mRNA in the hippocampus and cerebral cortex and of c-jun mRNA in the cerebral cortex. The induction of c-fos and c-jun mRNA was suppressed by administration of MK-801. Furthermore, PB withdrawal enhanced AP-1 DNA binding activity in the brain. The present findings suggest functional enhancement of glutamatergic neurotransmission during the development of PB withdrawal syndrome.

背景与目标： 我们研究了苯巴比妥（PB）依赖和戒断大鼠大脑中谷氨酸受体的变化，立即早期基因的表达以及AP-1 DNA结合活性，以研究PB戒断综合征中谷氨酸受体活化的可能。通过喂食药物混合的食物5周来制备PB依赖的大鼠。放射自显影分析表明，[3H（）-5-甲基-10,11-二氢-5H-二苯并[a，d]环庚烯-5,10-亚胺e（MK-801）与N-甲基- D-天冬氨酸（NMDA）受体，在PB依赖和24小时戒断大鼠的大脑皮层中显着增加。然而，在海马中的[3H] MK-801结合以及在海马和大脑皮层中的[3H] 6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）和[3H]海藻酸结合基本上没有变化。组。 PB抽搐发作后，海马和大脑皮层中c-fos mRNA的表达增加，大脑皮层中c-jun mRNA的表达增加。通过施用MK-801抑制了c-fos和c-jun mRNA的诱导。此外，PB撤离可增强大脑中AP-1 DNA的结合活性。目前的发现表明，在PB戒断综合征的发展过程中，谷氨酸能神经传递的功能增强。

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同源盒基因家族以复杂的模式在胚胎颅面外胚层和外间质内表达。先前的研究表明，Dlx-2对于鼠的第一和第二分支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Dlx-1和-2突变的小鼠的颅面表型。具有Dlx-1和Dlx-1和-2突变的小鼠的骨骼和软组织分析提供了其他证据，证明Dlx基因调节the弓的近现代模式。该分析还阐明了Dlx-1和Dlx-2在颅面发育中的独特作用和重叠作用。此外，缺乏Dlx-1和-2的小鼠具有独特的异常，包括不存在上颌磨牙。 Dlx-1和-2在近端和远端第一和第二弓形中表达，但仅近端区域异常。 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定要求的模型提供了证据。最后，Dlx-2，Dlx-1和-2突变体具有异位的头骨成分，类似于在系统发育较原始的脊椎动物中发现的骨骼和软骨。

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： 白介素-1β（IL-1beta）与肝脏疾病密切相关。 IL-1beta通过环状鸟苷3'，5'-单磷酸（cGMP）在血管平滑肌细胞中产生一氧化氮（NO），并使血管平滑肌松弛。在这项研究中，我们评估了IL-1β对培养的Ito细胞的松弛作用。从雄性Wistar大鼠的肝脏中分离出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的免疫定位和cGMP的荧光强度。用0、200和1,000 pmol / L IL-1beta处理Ito细胞，并在12小时后测量细胞内cGMP浓度。此外，在12小时内观察到用200和1,000 pmol / L IL-1beta处理且未用IL-1beta处理的Ito细胞，并且在添加IL-1beta之前和之后比较了同一个Ito细胞的面积。接下来，研究了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）对通过IL-1beta处理的Ito细胞松弛的影响。在Ito细胞中，观察到iNOS的免疫荧光，添加IL-1β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。与未治疗组相比，IL-1β治疗组的细胞面积显着增加。 L-1NMMA以剂量依赖的方式抑制了通过IL-1beta处理的Ito细胞的松弛，但被SNAP增强了。这些结果表明IL-1β在培养的Ito细胞中产生NO，并通过cGMP使细胞松弛。

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GABR beta1基因中的四核苷酸重复多态性与西班牙人群的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，因为已在患者中描述了严重的GABergic改变。尽管我们的结果并未显示出躁狂抑郁症与GABR beta1之间存在关联的明确证据，但我们发现女性亚人群中的患者与对照组之间存在显着差异。

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，它们的表达可以被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，这些顺式作用调控基元之一是X2-box，其与核因子X2（NF-X2）结合。在这里，我们介绍了编码NF-X2的全长cDNA克隆的分离和表征。该cDNA克隆通过表达cDNA克隆进行分离，并编码人c-Jun蛋白，该蛋白与c-Fos一起形成异二聚激活蛋白-1转录复合体。尽管B细胞中不存在c-Fos / c-Jun异二聚体，但它们在II类非表达细胞中形成并与X2-box结合。因此，c-Fos / c-Jun异二聚体可能有助于抑制DRA基因表达。

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： 目的：评估新型可生物降解的聚-L-乳酸（PLLA）吻合支架的技术可行性，血栓形成性和生物相容性。
方法：通过腹部中线切口将聚四氟乙烯分叉移植物植入17只猪。横向移植后，将17个316L不锈钢支架和17个PLLA支架随机植入两个both吻合部位，并在不进行血管造影的情况下在直视下用6毫米球囊展开。预期的随访结果是：6头接受口服乙酰水杨酸（ASA）的猪和7头接受ASA /氯吡格雷的猪。对4只接受ASA /氯吡格雷的猪进行了6周的随访。在研究结束时，将包含支架的节段进行外科手术切除并进行组织学处理，以测量平均腔直径，内膜厚度以及血管损伤和炎症评分。
结果：在所有动物中均未发生缝线破裂的情况下，支架植入取得了初步的技术成功。手术后3天有2头猪死亡（与支架无关）（A和B组为1只）。在第1周，仅使用ASA时，所有PLLA支架均显示血栓闭塞。相反，所有PLLA支架在同时使用ASA /氯吡格雷的情况下仍保持专利。无论抗血小板方案如何，所有金属支架均已获得专利。专利PLLA支架的平均腔直径（4.13 /-0.17 mm）在1周时可与金属支架（4.27 /-0.35 mm，p = 0.78）相媲美，但在6周时显着减小（3.21 // 0.44对4.19 /-） 0.18毫米，p = 0.005）。组织学分析显示没有过度后坐的迹象。与金属支架[1.27 /-0.44 mm（p <0.001）和0.18 /-0.04 mm（p = 0.006）相比，PLLA支架引起更高的炎症评分（1.79 /-0.56）和更多的内膜增生（0.34 /-0.11 mm）。分别]在6周。 PLLA和金属支架之间的血管损伤相当。
结论：在早期随访中，与金属支架相比，可生物降解的PLLA支架显示出更高的血栓形成性和通畅性降低。尽管ASA和氯吡格雷预防了血栓闭塞，但炎症反应和新内膜形成的增加仍然是PLLA支架的主要关注点。解决该问题的方法可能是将抗炎药掺入PLLA支架中。

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： ：已从苦瓜种子和果实中分离出一种新的人类免疫缺陷病毒（HIV）抑制剂并将其纯化至同质。该化合物MAP 30（Momordica抗HIV蛋白）是大约30 kDa的碱性蛋白。它通过以下方式表现出对无细胞HIV-1感染和复制的剂量依赖性抑制作用：（i）在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； （iii）HIV-1感染的H9细胞中的病毒相关逆转录酶（RT）活性。在这些试验中，抑制50％（ID50）所需的剂量分别为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 30可能是治疗HIV-1感染的有用治疗剂。已经确定了MAP 30的N-末端44个氨基酸的序列。

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： 背景：α-1肾上腺素受体亚型（高，低）的新型分类被应用于人类良性前列腺肥大（BPH）组织。
方法：使用3H-吡唑嗪通过放射性配体结合测定法检查人的BPH标本，并将这些数据与术前治疗进行比较。
结果：（1）Scatchard分析显示高亲和力位点（Kd：27.18 /-6.41 pM; Bmax：9.29 /-0.98 fM / mg蛋白;平均值/-SE）为alpha 1H，低亲和力位点（Kd ：prazosin：α1L亚型：4088.0 /-744.34 pM，Bmax：140.81 /-19.98 fM / mg蛋白）。 （2）在未经治疗的组（n = 5），α1受体阻滞剂组（n = 5）和抗雄激素组（n = 5）中，Kd和Bmax的差异无显着性，二者均为α1-高亲和力或α1-低亲和力亚型。 （3）以上两种肾上腺素受体亚型的苯氧基苯甲胺的pKi值不同。斯卡查德分析表明，在存在1 microM苯氧基苯扎明的情况下，α1高亲和力结合位点消失了，在存在1 microM苯氧基苯扎明的情况下，Kd和Bmax值几乎与两种亚型的α1低亲和力位点相同。 。
结论：根据对Prazosin的亲和力，人类BPH组织同时具有alpha 1H-和alpha 1L-肾上腺素受体亚型，只有一定浓度的苯氧基苯扎明才能完全抑制alpha 1H亚型。用α1受体阻滞剂治疗可能不会改变前列腺组织中α1肾上腺素能受体的状况。

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： ：到目前为止，主要针对HIV-1感染的描述都是基于生活在工业化国家中的高加索人。由于对巴巴多斯主要是黑人人群的钩端螺旋体病进行了研究，因此伊丽莎白女王医院（QEH）接受了急性发热性疾病的患者可获得血清。通过搜索510例已知HIV-1感染的成年患者的病历，我们确定了10例在首次发热HIV-1阳性测试之前或与其同时发生的急性发热疾病患者入院时就储存了血清的患者。血清学检查证实了9例原发性HIV-1感染，并提示第10例患者。这10例患者的临床特征与原发性HIV-1感染的先前描述相符，但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡，另一名患者在血清转化后3个月死亡。研究结果表明，严重的原发性HIV-1感染可能是相对罕见的事件，该病可能被误诊，只有在AIDS流行之前，病例才可能发生。
：回顾性分析了510例曾在伊丽莎白女王医院（QEH）住院的HIV-1阳性成年患者的病历，以确定是否有人因与原发性HIV-1感染诊断相符的疾病而入院。由被接纳患有急性发热性疾病的患者创建的血清库，并研究了钩端螺旋体病，为10例患者的原发性HIV-1感染提供了血清学证据。血清样本的血清学检测证实了9名患者的原发性HIV-1感染，而第十名患者则具有启发性。这10例患者的临床特征符合原发性HIV-1感染的早期描述，但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡，另一名患者在血清转化后3个月死亡。这些发现表明，严重的原发性HIV-1感染可能是相对罕见的事件，可能会误诊该病，并且直到艾滋病流行才可能发生。

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，被认为负责产生与菠萝蛋白酶处理的自体红细胞（Br-RBC）的天然自身抗体。在此表明，大量常规的CD5阴性脾脏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细胞产生的人口。但是，在体内用细菌脂多糖刺激可优先激活CD5 B细胞基团以分泌抗Br-RBC抗体。