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 objective of this study was to confirm whether hemoglobin (Hb) levels during chemoradiotherapy are associated with survival in patients with locally advanced cervical carcinoma and to assess impact of the Hb level on survival according to lymph node (LN) metastasis. A retrospective review of 85 cervical carcinoma patients treated with concurrent chemoradiotherapy was conducted. The stage of disease ranged between FIGO stage IB and stage IVA. Disease-free and overall survivals were evaluated by univariate and multivariate analyses. After median follow-up of 35.7 months, 24 patients developed recurrence of disease and 14 patients died from their disease. Stage, LN metastasis, and squamous cell carcinoma antigen and Hb levels during chemoradiation were correlated significantly with survival (P < 0.05). Maintenance of Hb above 10.0 g/dL was associated with better survival (P < 0.05). However, no such benefits were observed in patients with LN metastasis by magnetic resonance imaging (MRI). Multivariate Cox regression hazard model showed that Hb levels during chemoradiation were an independent prognostic factor in patients without LN metastasis by MRI. Maintenance of Hb during chemoradiation is of benefit in cervical carcinoma patients without LN metastasis but not with LN metastasis by MRI.

背景与目标： : 本研究的目的是确认放化疗期间血红蛋白 (Hb) 水平是否与局部晚期宫颈癌患者的生存相关，并根据淋巴结 (LN) 转移评估Hb水平对生存的影响。回顾性分析了85例同期放化疗治疗的宫颈癌患者。疾病的阶段介于FIGO IB期和IVA期之间。通过单变量和多变量分析评估无病生存率和总体生存率。中位随访35.7个月后，24例患者出现疾病复发，14例患者死于疾病。分期、LN转移、放化疗期间鳞状细胞癌抗原和Hb水平与生存率显著相关 (P <0.05)。Hb维持在10.0g/dL以上与较好的生存率相关 (P <0.05)。然而，通过磁共振成像 (MRI) 在LN转移患者中未观察到这种益处。多因素Cox回归风险模型显示，放化疗期间的Hb水平是MRI无LN转移患者的独立预后因素。化疗期间维持血红蛋白对无LN转移但无LN转移的宫颈癌患者有好处。

BACKGROUND & AIMS: INTRODUCTION:Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS:We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS:In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION:High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.

背景与目标：

BACKGROUND & AIMS: PURPOSE:To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the trabecular meshwork (TM). METHODS:Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human TM tissue and explant cultures of TM endothelial cells. Cultures of TM cells were treated with vehicle control or latanoprost acid for 24 hours. Real-time RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS:The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 and of TIMP-1 to -4 was present in TM tissue and cultures of TM cells. MMP-9 was not found. In control TM endothelial cells, the relative expression of MMP mRNA were MMP-2 and -14 > MMP-16, -19, and -24 > MMP-15 > MMP-11 and -17 > MMP-1 and -3 > MMP-12. The relative expressions of TIMP mRNA were TIMP-1 > TIMP-2 and -3 > TIMP-4. Latanoprost increased MMP-1 (in four of five cultures), MMP-3 (in four of five cultures), MMP-17 (in three of five cultures), MMP-24 (in all five cultures), TIMP-2, -3, and -4 expression (in three of five cultures); MMP-11 and -15 were downregulated. CONCLUSIONS:Contrary to the expected result, latanoprost seems to have a significant effect on TM cells. The transcription of the genes for MMP-1, -3, -17, and -24 is increased by latanoprost treatment. TIMP-2, -3, and -4 are also upregulated. The upregulation of these TIMPs may compensate for the increase of those MMPs. The absence of MMP-9 and concurrent upregulation of a greater number of TIMPs may explain the limited effect of latanoprost on TM outflow.

背景与目标：

BACKGROUND & AIMS: :Elucidation of the cellular basis of arrhythmias in ion channelopathy disorders is complicated by the inherent difficulties in studying human cardiac tissue. Thus we used a computer modeling approach to study the mechanisms of cellular dysfunction induced by mutations in inward rectifier potassium channel (K(ir))2.1 that cause Andersen-Tawil syndrome (ATS). ATS is an autosomal dominant disorder associated with ventricular arrhythmias that uncommonly degenerate into the lethal arrhythmia torsade de pointes. We simulated the cellular and tissue effects of a potent disease-causing mutation D71V K(ir)2.1 with mathematical models of human ventricular myocytes and a bidomain model of transmural conduction. The D71V K(ir)2.1 mutation caused significant action potential duration prolongation in subendocardial, midmyocardial, and subepicardial myocytes but did not significantly increase transmural dispersion of repolarization. Simulations of the D71V mutation at shorter cycle lengths induced stable action potential alternans in midmyocardial, but not subendocardial or subepicardial cells. The action potential alternans was manifested as an abbreviated QRS complex in the transmural ECG, the result of action potential propagation failure in the midmyocardial tissue. In addition, our simulations of D71V mutation recapitulate several key ECG features of ATS, including QT prolongation, T-wave flattening, and QRS widening. Thus our modeling approach faithfully recapitulates several features of ATS and provides a mechanistic explanation for the low frequency of torsade de pointes arrhythmia in ATS.

背景与目标： : 阐明离子通道病疾病中心律失常的细胞基础因研究人类心脏组织的固有困难而变得复杂。因此，我们使用计算机建模方法来研究由引起Andersen-Tawil综合征 (ATS) 的内向整流钾通道 (K(ir))2.1突变引起的细胞功能障碍的机制。ATS是一种常染色体显性遗传性疾病，与室性心律失常相关，通常退化为致死性心律失常。我们用人类心室肌细胞的数学模型和透壁传导的双齿瘤模型模拟了有效的致病突变D71V K(ir)2.1的细胞和组织效应。D71V K(ir)2.1突变导致心内膜下，中心肌和心外膜下肌细胞的动作电位持续时间显着延长，但并未显着增加复极的透壁离散度。在较短的周期长度上模拟D71V突变会在中段心肌中诱导稳定的动作电位交替，但不诱导心内膜下或心外膜下细胞。在透壁ECG中，动作电位交替体表现为缩写的QRS复合体，这是动作电位在中段心肌组织中传播失败的结果。此外，我们对D71V突变的模拟概括了ATS的几个关键ECG特征，包括QT延长，T波平坦化和QRS增宽。因此，我们的建模方法忠实地概括了ATS的几个特征，并为ATS中尖端扭转型心律失常的低频率提供了机械解释。

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: :Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

背景与目标： : 通过免疫组织化学构建组织微阵列 (tma) 以有效表征乳房中大量非侵入性上皮病变是一种吸引人的研究方法，但存在技术挑战。我们报告了方法学研究，以优化从大型乳腺癌病例对照研究中收集的非侵入性乳腺组织中构建TMAs的方法。使用具有2.0毫米直径针头的手动排列技术，我们从32名乳腺癌妇女获得的标本中构建了TMAs，这些标本包含以下目标 :( 1) 28个末端导管小叶单位 (TDLUs); (2) 28个原位导管癌和 (3) 23个浸润性癌。通过仔细的靶标选择，我们通过TMAs的第30节获得了约80% 的非侵入性靶标的持续保存。TDLU靶标的免疫组织化学染色显示肾小管30.8% 中的雌激素受体 (ER) 和50.0% 中的孕激素受体 (PR) 呈阳性染色。为了建立一种有效的方法来评估TDLUs中的染色结果，我们创建了一个分类评分系统来近似包含阳性染色细胞 (<10%，10% 至50%，> 或 = 50%) 的小管的百分比，并将结果与通过小管计数获得的结果进行比较。两种方法之间的比较表明，ER的70.8% 和PR染色的79.2% 完全一致，没有两类差异。来自单个块的相同组织类型 (TDLU或DCIS) 的多个 (最多4个) 非侵入性靶标中的ER/PR表达水平显示出良好的相关性。这些数据表明，尽管仔细选择了靶标，但产生非侵入性乳房结构的tma是可行的，并且此类核心的免疫染色可能允许对瘤周组织进行有效的免疫组织化学表征。需要对这种方法进行进一步的探索。

BACKGROUND & AIMS: :A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples. In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas. These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.

背景与目标： : 低度纤维粘液样肉瘤 (LGFMS) 的诊断仍然存在问题，因为其外观平淡无奇的组织学特征可能与其他良性或低度纤维粘液样病变相混淆。最近的细胞遗传学和分子分析表明，大多数lgfms具有特征性的染色体异常t(7;16)(q33;p11)，导致FUS-CREB3L2融合基因。然而，这种测定很少用于分析福尔马林固定的石蜡包埋的肿瘤样品。在本研究中，我们进行了逆转录聚合酶链反应分析，以使用来自16个lgfms的福尔马林固定，石蜡包埋的肿瘤组织标本 (包括3例巨大的胶原玫瑰花结) 检测FUS-CREB3L2融合转录本。新设计了引物，以特异性扩增先前报道的FUS-CREB3L2融合基因转录物的大部分连接区域。在14/16 (88%) 例LGFMS中检测到FUS-CREB3L2融合基因转录本。PCR产物的核苷酸序列分析表明，FUS外显子6或7的不同部分与CREB3L2外显子5的不同位点融合，产生12种不同的核苷酸序列。我们还测试了引物集以检测FUS-CREB3L1融合转录本，这是LGFMS中基因融合的罕见变体，尽管在任何情况下都没有鉴定出PCR产物。在123种其他软组织肿瘤中均未检测到FUS-CREB3L2的融合转录物，包括真丝样纤维瘤，粘液纤维肉瘤，软组织神经瘤和先天性或成人纤维肉瘤。这些数据表明，我们的逆转录-聚合酶链反应测定法是检测FUS-CREB3L2的可靠方法，因此可以帮助准确诊断LGFMS。

BACKGROUND & AIMS: BACKGROUND:Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials.

METHODS AND RESULTS:We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).

CONCLUSIONS:Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

背景与目标： 背景 : 尽管溶栓治疗在降低急性心肌梗死死亡率方面的益处已得到充分证实，但在大型试验中，出血类型和出血危险因素的描述较少。
方法和结果 : 在GUSTO-I急性心肌梗死溶栓试验中，我们分析了41,021名患者的基线特征，结局和出血发生率，按位置，严重程度和治疗分配。在40,903例有完整数据的患者中，1.2% 例严重出血，11.4% 例在不同部位出现中度出血。最常见的出血来源与手术有关。溶栓方案与出血发生率密切相关; 链激酶加静脉肝素以及链激酶和组织型纤溶酶原激活剂加静脉肝素联合治疗的出血相对较多。在多变量分析中，出血的四个最有效的独立预测因子是年龄较大，体重较轻，女性和非洲血统; 当对未接受侵入性操作的患者进行多变量分析时，它们仍然是出血的最重要预测因子。严重出血的存在与其他不良结果 (复发事件，左心室功能障碍，心律失常或中风) 相关。
结论 : 该人群出血的重要预测因素是年龄增加，体重减轻，女性，非洲血统，经历侵入性手术。其他非出血性不良临床结局与中度和重度出血相关，而中度和重度出血又与30天时的住院时间和死亡率增加相关。

BACKGROUND & AIMS: BACKGROUND AND AIMS OF THE STUDY:Bovine and porcine pericardial tissues stabilized by dye-mediated photooxidation have found application as bioprosthetic heart valve material.

METHODS:To help predict clinical performance, a series of tests were performed to assess the biocompatibility and immunologic properties of these materials.

RESULTS AND CONCLUSIONS:Photooxidized bovine or porcine pericardium sterilized with an iodine-based solution were found to be non-cytotoxic, non-hemolytic, and non-mutagenic. Oil or saline extracts of these tissues passed tests for intracutaneous toxicity (irritation), acute systemic toxicity, and subchronic toxicity. Histopathology of 90-day implants of these tissues in the rabbit model demonstrated no significant macroscopic reaction and only slight microscopic response. Using a rabbit model to assess immune response, both bovine and porcine pericardial tissues elicited low levels of antibody. Furthermore, tissue photooxidation or iodine sterilization did not increase the overall level of antibodies. Glutaraldehyde-treated tissue also elicited low antibody levels which were higher than photooxidized tissue-induced levels. Absorption studies indicated that the photooxidation process may generate new epitopes, possibly collagen cross-links. Using the juvenile sheep model to assess in vivo performance, bioprosthetic valves made with photooxidized tissue were implanted and allowed to serve as functional implants for up to two years. Upon explant, the photooxidized pericardial leaflets were found to be non-calcific and partially covered with a layer of host cells. Histological cross-sections stained with von Willebrand's factor confirmed this layer as endothelial cells.

背景与目标： 研究的背景和目的 : 通过染料介导的光氧化作用稳定的牛和猪心包组织已被用作生物人工心脏瓣膜材料。
方法 : 为了帮助预测临床表现，进行了一系列测试以评估这些材料的生物相容性和免疫学特性。
结果和结论 : 发现用碘基溶液灭菌的光氧化牛或猪心包具有非细胞毒性，非溶血性，和非诱变性。这些组织的油或盐水提取物通过了皮内毒性 (刺激)，急性全身毒性和亚慢性毒性的测试。在兔模型中，这些组织的90天植入物的组织病理学没有明显的宏观反应，只有轻微的微观反应。使用兔模型评估免疫反应，牛和猪心包组织均引起低水平的抗体。此外，组织光氧化或碘灭菌不会增加抗体的总体水平。戊二醛处理的组织也引起低抗体水平，该水平高于光氧化组织诱导的水平。吸收研究表明，光氧化过程可能会产生新的表位，可能是胶原蛋白交联。使用幼年绵羊模型评估体内性能，将用光氧化组织制成的生物人工瓣膜植入并作为功能性植入物长达两年。外植体后，发现光氧化的心包小叶是非钙化的，并部分覆盖有一层宿主细胞。用von Willebrand因子染色的组织学横截面证实了该层为内皮细胞。

BACKGROUND & AIMS: :In the last few years fetal magnetic resonance imaging (MRI) has been proposed as a second level technique in the evaluation of fetal brain anomalies. It has been demonstrated that MRI is highly accurate in illustrating the morphologic changes of developing brain and fetal brain abnormalities being a useful procedure when ultrasonography is inconclusive or doubtful. Starting from the 19-20 weeks gestational age (GA), MRI can reliably depict fetal brain anatomy and locating pathology, offering a robust and reliable tool in the assessment of fetal CNS diseases. In this review both in vivo MRI quantitative and qualitative data about fetal cerebellar development are presented and compared with ultrasonography data. Fetal cerebellar development is gradual, steady, and largely comparable to the development of the supratentorial brain. Archicerebellar (flocculo-nodular lobe) and paleocerebellar (vermis) structures develop first, whereas neocerebellum (cerebellar hemispheres) develop slowly and largely after birth.

背景与目标： : 在过去的几年中，胎儿磁共振成像 (MRI) 已被提议作为评估胎儿大脑异常的第二级技术。已经证明，当超声检查不确定或可疑时，MRI在说明发育中的大脑和胎儿大脑异常的形态变化方面非常准确，这是一种有用的方法。从19-20周的胎龄 (GA) 开始，MRI可以可靠地描述胎儿的大脑解剖结构和定位病理，为评估胎儿中枢神经系统疾病提供了可靠可靠的工具。在这篇综述中，介绍了有关胎儿小脑发育的体内MRI定量和定性数据，并将其与超声检查数据进行了比较。胎儿小脑的发育是渐进的，稳定的，并且在很大程度上与幕上大脑的发育相当。小脑 (小脑结节叶) 和古小脑 (ver) 结构首先发育，而新脑 (小脑半球) 在出生后缓慢且大部分发育。

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：

BACKGROUND & AIMS: :Plectin is a widely expressed protein that is very large in size and that has all the attributes of a multifunctional crosslinking and organizing element of the cytoskeleton. It displays a multidomain structure, versatile binding activities, and subcellular localizations that enable it to strengthen cells against mechanical stress forces. Moreover, hereditary gene defects in plectin cause epidermolysis bullosa simplex (EBS)-MD, a severe skin blistering disease with muscular dystrophy. Here we report the analysis of the exonintron organization of the rat plectin gene and the identification of several different isoforms on the transcriptional level. We show that of 35 coding exons identified, 4 serve as alternative first exons splicing into the same successive exon 2, which is the first of 7 exons encoding a highly conserved actin-binding domain. RNase protection mapping of transcripts containing 3 of the identified 4 alternate first exons revealed their coexpression in rat glioma C6 cells and in a series of different rat tissues that we examined. Significant variations in expression levels of first exons indicated the possibility of tissue-specific promoter usage. In addition, plectin splice variants lacking exon 31 (> 3 kb), which encodes the entire rod domain of the molecule, were identified in a variety of rat tissues. This study provides first insights into a complex plectin gene regulatory machinery with similarities to that of dystrophin.

背景与目标： : pletin是一种广泛表达的蛋白质，其大小非常大，并且具有细胞骨架的多功能交联和组织元件的所有属性。它显示出多域结构，多种结合活性和亚细胞定位，使其能够增强细胞抵抗机械应力的能力。此外，plectin的遗传性基因缺陷会导致大疱性表皮松解症 (EBS)-MD，这是一种伴有肌营养不良的严重皮肤水疱性疾病。在这里，我们报告了对大鼠plectin基因外显子组织的分析，并在转录水平上鉴定了几种不同的同工型。我们显示，在鉴定出的35个编码外显子中，有4个作为替代的第一个外显子拼接成相同的连续外显子2，这是编码高度保守的肌动蛋白结合域的7个外显子中的第一个。包含鉴定出的4个交替第一外显子中的3个的转录物的RNase保护作图显示了它们在大鼠神经胶质瘤C6细胞和我们检查的一系列不同大鼠组织中的共表达。第一个外显子表达水平的显着变化表明使用组织特异性启动子的可能性。此外，在多种大鼠组织中鉴定出缺少外显子31 (> 3 kb) 的pletin剪接变体，该外显子编码分子的整个杆结构域。这项研究提供了与肌营养不良蛋白相似的复杂pletin基因调控机制的第一个见解。

BACKGROUND & AIMS: OBJECTIVES:This prospective study was designed to assess the sensitivity and specificity of Doppler ultrasound parameters in the diagnosis of cirrhosis and portal hypertension. METHODS:Portal and hepatic arterial Doppler ultrasound was performed on 76 patients with cirrhosis and esophageal varices and on 73 age- and sex-matched controls. The parameters evaluated were portal venous velocity and hepatic arterial pulsatility index. The liver vascular index was calculated as the ratio of portal venous velocity to hepatic arterial pulsatility index. RESULTS:Portal venous velocity was significantly lower (11.0 +/- 2.4 vs 15.9 +/- 2.8 cm/s, p < 0.001) and hepatic arterial pulsatility index was significantly higher (1.28 +/- 0.18 vs 0.95 +/- 0.17,p < 0.001) in patients than in controls. Thus, the liver vascular index was significantly lower in patients than in controls (8.7 +/- 2.1 vs 17.2 +/- 4.3 cm/s, p < 0.001). The sensitivity and specificity of these parameters in the detection of cirrhosis and portal hypertension was then analyzed with the receiver operating characteristic curve. The best cut-off values were considered to be 13 cm/se of portal venous velocity and 1.1 of hepatic arterial pulsatility index, showing a sensitivity and specificity of 83, 85, 84, and 81%, respectively. The best cut-off value of the liver vascular index was 12 cm/s with a sensitivity and specificity of 97 and 93%, respectively. CONCLUSIONS:The liver vascular index is a high sensitive and specific Doppler ultrasound parameter in the diagnosis of cirrhosis and portal hypertension.

背景与目标：

BACKGROUND & AIMS: :The sodium iodide symporter (NIS) mediates iodide (I(-)) transport in the thyroid gland and other tissues and is of increasing importance as a therapeutic target and nuclear imaging reporter. NIS activity in vitro is currently measured with radiotracers and electrophysiological techniques. We report on the development of a novel live cell imaging assay of NIS activity using the I(-)-sensitive and genetically encodable yellow fluorescent protein (YFP) variant YFP-H148Q/I152L. In FRTL-5 thyrocytes stably expressing YFP-H148Q/I152L, I(-) induced a rapid and reversible decrease in cellular fluorescence characterized by 1) high affinity for extracellular I(-) (35 muM), 2) inhibition by the NIS inhibitor perchlorate, 3) extracellular Na(+) dependence, and 4) TSH dependence, suggesting that fluorescence changes are due to I(-) influx via NIS. Individual cells within a population of FRTL-5 cells exhibited a 3.5-fold variation in the rate of NIS-mediated I(-) influx, illustrating the utility of YFP-H148Q/I152L to detect cell-to-cell difference in NIS activity. I(-) also caused a perchlorate-sensitive decrease in YFP-H148Q/I152L fluorescence in COS-7 cells expressing NIS but not in cells lacking NIS. These results demonstrate that YFP-H148Q/I152L is a sensitive biosensor of NIS-mediated I(-) uptake in thyroid cells and in nonthyroidal cells following gene transfer and suggest that fluorescence detection of cellular I(-) may be a useful tool by which to study the pathophysiology and pharmacology of NIS.

背景与目标： : 碘化钠同向转运体 (NIS) 介导碘 (I(-)) 在甲状腺和其他组织中的转运，作为治疗靶标和核成像报告基因的重要性日益提高。目前使用放射性示踪剂和电生理技术测量体外的NIS活性。我们报告了使用I(-) 敏感且可遗传编码的黄色荧光蛋白 (YFP) 变体YFP-H148Q/I152L对NIS活性进行新型活细胞成像测定的开发。在稳定表达YFP-H148Q/I152L的FRTL-5甲状腺细胞中，I(-) 诱导细胞荧光的快速和可逆降低，其特征是1) 对细胞外I(-) (35 muM) 的高亲和力，2) NIS抑制剂高氯酸盐的抑制，3) 细胞外Na(+) 依赖性，和4) TSH依赖性，表明荧光变化是由于I(-) 通过NIS流入所致。FRTL-5细胞群内的单个细胞表现出NIS介导的I(-) 流入速率的3.5倍变化，说明YFP-H148Q/I152L用于检测NIS活性的细胞间差异。I(-) 还导致表达NIS的COS-7细胞中YFP-H148Q/I152L荧光的高氯酸盐敏感降低，但在缺乏NIS的细胞中不引起。这些结果表明，YFP-H148Q/I152L是基因转移后甲状腺细胞和非甲状腺细胞中NIS介导的I(-) 摄取的敏感生物传感器，并表明细胞I(-) 的荧光检测可能是研究的有用工具。NIS的病理生理学和药理学。