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： Interleukin-1 α (IL-1 α) 在体外诱导多种良性细胞类型和一些但不是全部恶性细胞系中的细胞运动。这项研究表征了表达I型和II型IL-1受体的侵袭性人类黑素瘤细胞系的IL-1 α 诱导的运动。我们测试了单克隆抗体 (包括针对I型和II型IL-1受体的功能阻断moab) 对黑色素瘤细胞运动的影响，以确定哪种受体参与IL-1 α 诱导的黑色素瘤细胞运动的信号转导。IL-1 α 以剂量依赖的方式显著增加MM-RU黑素瘤细胞迁移，使用改进的Boyden室测定法，浓度低于显著抑制细胞生长的浓度的10至100倍。计算机辅助延时图像分析表明，通过中和针对IL-1 α 的抗体，运动性以剂量依赖的方式受到抑制。针对I型或II型IL-1受体的功能阻断单克隆抗体显示出对细胞因子诱导的增强细胞迁移的显着抑制。当两种anti-IL-1受体抗体加在一起时，运动反应完全阻断到控制水平。总之，这些数据表明，IL-1 α 诱导的MM-RU黑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-1 α 或阻断一种或两种IL-1受体而显着抑制运动，表明IL-1-induced信号在诱导黑色素瘤细胞迁移中的整合。

BACKGROUND & AIMS: :Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression in endometrial malignancies and their relation to clinical and histologic parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with endometrial carcinoma treated between 1999 and 2004 were stained with specific monoclonal antibodies. The tumors were grouped according to the FIGO classification. The staining results were compared to histologic and clinical data. Semiquantitative analysis of MMP and TIMP expression showed a significant difference in TIMP-2 expression according to the histologic subtype (P = 0.03) and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2 expression increased and TIMP-2 expression fell as the histologic grade increased (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02), and lymph node metastasis (P = 0.0003). These results support the involvement of MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low TIMP-2 expression were the most potent markers of endometrial tumors with a high risk of local and distant spread.

背景与目标： : 基质金属蛋白酶 (MMPs) 的表达与妇科肿瘤的侵袭性有关。这项研究的目的是确定子宫内膜恶性肿瘤中金属蛋白酶 (TIMP)-1和TIMP-2的MMP-2，MMP-7，MMP-9和组织抑制剂及其与临床和组织学参数的关系。用特异性单克隆抗体对来自50例1999年和2004例子宫内膜癌患者的福尔马林固定，石蜡包埋的肿瘤样品进行染色。根据FIGO分类对肿瘤进行分组。将染色结果与组织学和临床数据进行比较。MMP和TIMP表达的半定量分析显示，根据组织学亚型，TIMP-2表达存在显着差异 (P = 0.03)，并且MMP-9表达存在差异的趋势 (P = 0.05)。随着组织学分级的增加，MMP-2表达增加，TIMP-2表达下降 (分别为P = 0.0007，P <0.0001)。MMP-2表达与淋巴结转移相关 (P = 0.04)，而TIMP-2表达与肌层浸润深度相关 (P = 0.01)，血管淋巴间隙受累 (P = 0.02) 和淋巴结转移 (P = 0.0003)。这些结果支持MMPs和TIMPs参与子宫内膜肿瘤的生长和进展。高MMP-2和低TIMP-2表达是子宫内膜肿瘤的最有效标志物，具有局部和远处扩散的高风险。

BACKGROUND & AIMS: The effect of nutritional status on IGF-I mRNA expression in the liver and brain of juvenile barramundi (Lates calcarifer) was investigated. Fish were either fed a satiety ration (SAT) or starved (STV) for 6 weeks. Starved fish demonstrated significantly lower condition factor and hepatic IGF-I mRNA expression at 3 and 6 weeks, when compared with the SAT group. IGF-I mRNA expression in the brain was 10 fold lower than the liver and was not affected by ration size. These results suggest the liver is the major site of IGF-I mRNA synthesis and hepatic but not brain IGF-I mRNA expression is regulated by food availability in juvenile barramundi.

背景与目标： 研究了营养状况对幼年barramundi (Lates calcarifer) 肝脏和大脑中igf-i mRNA表达的影响。对鱼喂食饱腹感 (SAT) 或饥饿 (STV) 6周。与SAT组相比，饥饿的鱼在3周和6周时表现出明显较低的条件因子和肝igf-i mRNA表达。大脑中igf-i mRNA的表达比肝脏低10倍，不受日粮大小的影响。这些结果表明，肝脏是igf-i mRNA合成的主要部位，而肝脏而不是大脑igf-i mRNA的表达受幼年barramundi食物的调节。

BACKGROUND & AIMS: :The chromosome of Streptomyces coelicolor A3(2), a model organism for the genus Streptomyces, contains a cryptic type I polyketide synthase (PKS) gene cluster which was revealed when the genome was sequenced. The ca. 54-kb cluster contains three large genes, cpkA, cpkB and cpkC, encoding the PKS subunits. In silico analysis showed that the synthase consists of a loading module, five extension modules and a unique reductase as a terminal domain instead of a typical thioesterase. All acyltransferase domains are specific for a malonyl extender, and have a B-type ketoreductase. Tailoring and regulatory genes were also identified within the gene cluster. Surprisingly, some genes show high similarity to primary metabolite genes not commonly identified in any antibiotic biosynthesis cluster. Using western blot analysis with a PKS subunit (CpkC) antibody, CpkC was shown to be expressed in S. coelicolor at transition phase. Disruption of cpkC gave no obvious phenotype.

背景与目标： : 链霉菌属链霉菌A3(2) 的染色体是链霉菌属的模式生物，包含一个隐秘的I型聚酮化合物合酶 (PKS) 基因簇，该基因簇在基因组测序时被揭示。ca。54kb簇包含三个大基因，cpkA，cpkB和cpkC，编码PKS亚基。在计算机分析中，合酶由一个加载模块，五个延伸模块和一个独特的还原酶组成，作为末端结构域，而不是典型的硫酯酶。所有酰基转移酶结构域都对丙二酰延伸剂具有特异性，并且具有b型酮还原酶。在基因簇中还鉴定了定制和调节基因。令人惊讶的是，一些基因与在任何抗生素生物合成簇中不常见的初级代谢物基因显示出高度相似性。使用带有PKS亚基 (CpkC) 抗体的蛋白质印迹分析，显示CpkC在过渡期在coelicolor中表达。cpkC的破坏没有明显的表型。

BACKGROUND & AIMS: UNLABELLED:Radiolabeled benzamides have recently been introduced for the detection of melanoma. We evaluated the potential clinical applicability of 123I-N-(2-diethylaminoethyl) 4-iodobenzamide ([123I]IDAB) for SPECT imaging of ocular melanoma.

METHODS:Fourteen patients were studied, 10 with or suspected of malignant ocular melanoma and four with ocular naevi. All patients underwent SPECT imaging of the head and whole-body scintigraphy 4-5 hr after injection of 170 MBq [123I]IDAB.

RESULTS:A definite tracer hyperfixation was observed in the pathological eye in 9 of 10 (90%) patients with ocular melanoma. The pathological-to-normal eye ratio averaged 1.46 (range 1.07-2.86). The melanoma nature of the scintigraphic lesions was confirmed after enucleation in eight cases and by clinical evolution in two. A false-negative scan was reported in a patient with a small and hypochromic lesion. In patients with ocular naevi, no false-positive scintigrams were documented.

CONCLUSION:Iodine-123-IDAB scintigraphy may contribute significantly to decide about enucleation in cases where some doubt persists with conventional techniques.

背景与目标： 未标记 : 最近已引入放射性标记的苯甲酰胺用于检测黑色素瘤。我们评估了123I-N-(2-二乙氨基乙基) 4-碘苯甲酰胺 ([123I]IDAB) 在眼部黑色素瘤SPECT成像中的潜在临床适用性。
方法 : 研究了14名患者，10例患有或怀疑患有恶性眼部黑色素瘤，4例患有眼部恶性黑色素瘤。注射170 MBq [123I]IDAB后4-5小时，所有患者均接受了头部SPECT成像和全身闪烁显像。
结果 : 在10例 (90% 例) 眼部黑色素瘤患者中，有9例在病理眼中观察到了明确的示踪剂超固定。病理与正常眼的比率平均为1.46 (范围1.07-2.86)。闪烁显像病变的黑色素瘤性质在8例摘除后得到证实，两例通过临床进化得到证实。在一名患有小的低色度病变的患者中报告了假阴性扫描。在患有眼痣的患者中，没有记录假阳性闪烁图。
结论 : 在常规技术仍然存在疑问的情况下，Iodine-123-IDAB闪烁显像可能会大大有助于决定摘除。

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细节知之甚少。该过程的一部分受异质核核糖核蛋白A2 (hnRNP A2) 的活性控制。本研究研究了hnRNP A2在HeLa细胞中真正的前病毒表达中的作用。使用免疫荧光和荧光原位杂交技术，我们显示了HIV-1-expressing细胞中hnRNP A2表达的敲低导致HIV-1基因组RNA在与微管组织中心 (MTOC) 相对应的独特细胞质空间中快速积累。即使在hnRNP A2-response元件 (A2RE) 中携带突变的前病毒的表达过程中，由于hnRNP A2敲除，RNA也会在细胞核中离开并在MTOC区域积累，其表达导致基因组RNA的核保留。我们还证明hnRNP A2表达是细胞质中来自MTOC的基因组RNA下游运输所必需的。hnRNP A2敲低的结果和Rab7-interacting溶酶体蛋白的过表达在MTOC上的基因组RNA定位对pr55Gag的合成几乎没有影响，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定位调节病毒组装，并且MTOC充当HIV-1基因组RNA从细胞核退出后会聚的中心位点，宿主蛋白hnrnpa2在将其带到和从细胞中的该位点中起着核心作用。

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) 依赖性和退缩大鼠大脑中谷氨酸受体的变化，即刻早期基因的表达以及AP-1的DNA结合活性，以研究谷氨酸受体激活在PB戒断综合征中的可能参与。通过喂养混合药物的食物5周制备PB依赖性大鼠。放射自显影分析显示，N-甲基-d-天冬氨酸 (NMDA) 受体拮抗剂 [3H(+)-5-甲基-10,11-二氢-5H-二苯并 [a，D] cyclohepten-5，10-敏e (MK-801) 的结合，PB依赖性和24h撤回大鼠的大脑皮层显着增加。然而，[3h] MK-801在海马和 [3H]6-氰基-7-硝基喹喔啉-2结合，海马和大脑皮层中的3-二酮 (CNQX) 和 [3H] 海藻酸结合在两组中基本上没有变化。铅戒断发作后，海马和大脑皮层中c-fos mRNA的表达增加，大脑皮层中c-6月mRNA的表达增加。诱导c-MK-801可抑制fos和c-6月mRNA。此外，铅戒断增强了大脑中的AP-1 DNA结合活性。目前的发现表明，在铅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。

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。

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。

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。

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。

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。

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。

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。