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。

BACKGROUND & AIMS: BACKGROUND:Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE:To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN:Prospective, double-blind, placebo-controlled trial. SETTING:Tertiary referral university hospital. PATIENTS:A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS:Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS:Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS:There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS:Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.

背景与目标： 背景：尽管最近在技术和患者选择方面已有改进，但ERCP后胰腺炎仍然是ERCP最常见和最可怕的并发症。最近的研究表明，用三硝酸甘油酯（GTN）进行预处理可以预防ERCP后胰腺炎并提高插管成功率。
目的：评价经皮GTN对ERCP插管成功和ERCP术后胰腺炎的影响。
设计：一项前瞻性，双盲，安慰剂对照试验。
单位：大专转诊大学医院。
患者：共有318例患者（平均年龄62岁，女性占61％）被随机分配到活动组（n = 155）或安慰剂组（n = 163）。
干预措施：主动贴片（GTN）与安慰剂贴片。
主要观察指标：排尿时间和成功率。 ERCP后胰腺炎发生率。
结果：主动或安慰剂组之间在以下方面没有显着差异：成功的初始插管（96.8％vs 98.8％），深层插管（96.1％vs 98.8％），成功插管的时间，使用导丝（27％vs 25％）或针刀（13％比13％）以及ERCP后胰腺炎（安慰剂患者为7.4％，活动患者为7.7％）。多变量分析确定女性，年轻患者，胰腺造影，乳头尝试次数以及混浊后胰管排空不良是ERCP后胰腺炎的危险因素。在任何已确定的高危人群中，经皮GTN均不能减轻ERCP后胰腺炎的发生。
结论：无论是普通患者还是高危患者，经皮GTN均不能提高ERCP插管成功率或预防ERCP术后胰腺炎。

BACKGROUND & AIMS: :Matrix metalloproteinases (MMPs) have been the subject of intense research because of their roles in tumor metastasis and in the rise and spread of degenerative diseases such as osteo- and rheumatoid arthritis. A preliminary class of 140 druglike, small-molecule matrix metalloproteinase-3 inhibitors, intended as starting scaffolds for optimization and synthesis, has been designed in silico using a series of highly predictive three-dimensional quantitative structure-activity relationship models, including comparative molecular field analysis and comparative molecular similarity indices analysis, with docking and scoring. Thalidomide was chosen as the skeleton on which to base the new lead series, as it moderately inhibits MMP-3, is antiangiogenic, and lends itself easily to structural modifications. Most of the new compounds demonstrate medium to high predicted biological activity and good bioavailability as estimated by the octanol-water partition coefficient ClogP. Compound 102 in particular exhibits extremely favorable predicted activity against MMP-3; is moderately bioavailable; satisfies Lipinski's Rule of Five; and shows promise for further optimization, synthesis, and experimental evaluation as a potential adjunct anticancer or antirheumatic therapeutic.

背景与目标： ：基质金属蛋白酶（MMP）由于其在肿瘤转移中以及在变性疾病（例如骨和类风湿性关节炎）的发生和扩散中的作用而受到了广泛的研究。已在计算机上使用一系列高度预测的三维定量结构-活性关系模型（包括比较分子场）在计算机上设计了初步的140类药物样小分子基质金属蛋白酶3抑制剂，旨在作为优化和合成的起始支架。分析和比较分子相似性指数分析，以及对接和评分。选择沙利度胺作为新铅系列的基础，因为它能适度抑制MMP-3，具有抗血管生成作用，并易于进行结构修饰。正如辛醇-水分配系数ClogP所估计的那样，大多数新化合物都具有中等至较高的预测生物活性和良好的生物利用度。特别地，化合物102对MMP-3表现出非常有利的预测活性。具有中等生物利用度；满足Lipinski的五法则；并有望进一步优化，合成和进行实验评估，作为潜在的辅助抗癌药或抗风湿药。

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。