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。该过程的一部分由异质核糖核蛋白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在MTOC区域积聚，其表达会导致基因组RNA的核保留。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expression of immediate early genes, and AP-1 DNA binding activity in the brains of phenobarbital (PB)-dependent and -withdrawn rats to investigate the possible involvement of activation of glutamate receptors in PB withdrawal syndrome.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，结合物[3H（）-5-甲基-10,11-二氢-5H-二苯并[a，d]环庚烯-5,10-亚胺e（MK-801）是一种N-甲基-拮抗剂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branch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，类似于在系统发育上较原始的脊椎动物中发现的骨骼和软骨。

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（HCL）含量增加所定义的，并且经常在包括2型糖尿病在内的胰岛素抵抗状态中观察到。饮食中饱和脂肪过多会大大增加HCL的积累。 HCL水平升高主要是肝脏胰岛素抵抗的原因，这可能是由于游离脂肪酸在肝脏中的分配（脂肪溢出）和脂肪细胞因子的失衡（脂联素减少和/或促炎性细胞因子增加）引起的。游离脂肪酸和脂肪细胞因子均激活包括蛋白激酶C，转录因子核因子kappaB和c-Jun N端激酶1在内的炎症途径，从而可以加速肝脂肪变性发展为非酒精性脂肪性肝炎和肝硬化。质子磁共振波谱使量化HCL浓度和检测临床环境中这些浓度的微小变化成为可能。适度低热量，低脂肪饮食可将HCL水平降低约40-80％，同时最多可减少8％的体重。噻唑烷二酮类药物（例如吡格列酮和罗格列酮）治疗可通过调节2型糖尿病的胰岛素敏感性和脂肪组织的内分泌功能将HCL水平降低30-50％。二甲双胍在不影响HCL水平的情况下改善了肝胰岛素的作用，而胰岛素输注67 h使HCL水平增加了约18％。此外，在用胰岛素治疗的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，因此代表了胰岛素抵抗和2型糖尿病的重要治疗靶标。

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： 口唇瘤是一种独特的肿瘤，其特征是增殖的嗜碱性细胞和诊断性影子细胞由双重人群组成，据信它们是由毛发基质引起的。正常的头发基质会经历特定的生长（生长期），消退（退化期）和静止（休止期）周期，这些周期受程序性细胞死亡（细胞凋亡）的调节。 bcl-2是一种原癌基因，有助于抑制良性和恶性肿瘤中的细胞凋亡。此外，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，我们使用免疫组化方法研究了10例经组织学证实的pilomatricoma的bcl-2表达。研究设计包括阳性和阴性对照。 bcl-2免疫染色强烈修饰了我们系列中的所有pilomatricomas。根据bcl-2染色增加的发现，我们得出结论，凋亡的错误抑制是导致毛细血管瘤的发病原因。

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-1β在血管平滑肌细胞中产生一氧化氮（NO），并通过环状鸟苷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-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GAB能改变。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: 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： GATA家族的脊椎动物DNA结合调节蛋白在不同的组织中以及在不同的发育时期表达。但是，这些蛋白质的DNA结合区具有相当的同源性，可以识别相当相似范围的DNA序列基序。 DNA结合是通过两个结构域介导的，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末端指可以有助于结合的特异性和强度，但它不能独立地结合，而C末端指对于结合既是必需的又是足够的。在这里，我们表明，尽管对于GATA-1的N端手指来说确实如此，但GATA-2和GATA-3的手指却能够强烈独立地结合，并优先选择基序GATC。结合需要在N末端指形物的两侧都存在两个基本区域。在GATA-1 N端手指附近缺少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一个基序的新变体，该变体先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区分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。

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头猪。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）。 ，分别在第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。解决此问题的方法可能是将抗炎药掺入PLLA支架中。

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： ：我们的目标是通过非侵入性高分辨率（117 x 117 x 70 microm）磁共振（microMRI）和诱发视觉系统（VEP）技术追踪转基因小鼠的运动异常，然后部分恢复。我们使用经工程改造过表达Golli-mbp基因复合物产物Golli J37（特别是在少突胶质细胞中）的JOE（用于J​​37 golli过表达）转基因小鼠。从21岁到75天大，使用11.7 T扫描仪上的非侵入性体内VEP和3D T2加权显微MRI对个体JOE转基因及其未受影响的兄弟姐妹进行跟踪研究，我们认为这是同类研究中的首次纵向研究。显微MRI数据表明，在峰值髓鞘形成期（21-42天）期间出现了明显的整体性低髓鞘形成，与对照组相比，JOE小鼠在以后的年龄（> 60天）中得到了部分纠正。这些显微MRI数据与[Campagnoni AT（1995）“髓鞘形成的分子生物学”）有很好的相关性。在：Ransom B，Kettenmann H（eds）Neuroglia-专着中。牛津大学出版社，伦敦，第555-570页]髓磷脂染色，[Campagnoni AT，Macklin WB（1988）髓磷脂蛋白基因表达的细胞和分子方面。 [Mol Neurobiol 2：41-89]在髓鞘形成高峰期发生短暂的意向性震颤，此现象在以后的年龄有所减轻，[Lees MB，Brostoff SW（1984）Proteins in髓磷脂。在：莫雷尔（编辑）髓磷脂。 [Plenum Press，纽约和伦敦，第197-224页] VEP均表明JOE小鼠的CNS髓磷脂发育显着延迟和持续性髓鞘减少。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迟缓的小鼠大脑中髓鞘形成的增加。

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蛋白质）是约30 kDa的碱性蛋白质。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: :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： ：分子生物学技术被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，人细小病毒B19，水痘-带状疱疹病毒和风疹病毒在怀孕期间发生的感染，用于诊断和管理逆转录病毒感染（HIV和HTLV）和肝炎（H​​BV和HCV），用于乳头瘤病毒分型并检测病毒与临床表现之间的联系（心肌病或胰岛素依赖型糖尿病与柯萨奇病毒B：卡波西氏肉瘤伴HHV 8）或调查环境污染病毒。这些新的定性和定量分子标记代表了病毒诊断研究领域，感染过程中病毒载量的监测，病毒疾病的治疗控制和病毒传播的流行病学的重要进展。使用可用的市售试剂和试剂盒可获得标准化和自动化。

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。