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: Recent evidence suggests that Chlamydia trachomatis can persist in the female upper genital tract in an unculturable state. Since unsuspected C. trachomatis infection has been associated with adverse in-vitro fertilization (IVF) outcome we sought to detect further evidence of C. trachomatis in the genital tracts of women undergoing IVF. The prevalence and distribution of antibodies to the major structural proteins of C. trachomatis in paired follicular fluid and sera of women undergoing IVF were examined. Sera and follicular fluid samples from 149 women were assayed for immunoglobulin (Ig)G and IgA antibodies to two C. trachomatis antigens, the major outer membrane protein (MOMP) and a recombinant lipopolysaccharide (rLPS) fragment. Additionally, the expression of human 60 kDa heat shock protein (hsp 60) in follicular fluid was determined. All cervical and follicular fluid samples were negative for C. trachomatis by polymerase chain reaction, ligase chain reaction and DNA probe. Sera from 60% of the subjects were positive for antichlamydial rLPS IgG; 36% were positive for anti-MOMP IgG. Similarly, rLPS-directed and MOMP-directed IgA were detected in sera of 34 and 14% of the subjects respectively. IgG antibodies to MOMP and rLPS were detected in 42 and 41% of the follicular fluid examined respectively. Anti-MOMP IgA was identified in 8.7% of the follicular fluid while 27.5% were positive for anti-rLPS IgA. Human hsp 60 expression was documented in 11.6% of the follicular fluid tested. IgA antibodies to both MOMP (P = 0.03) and rLPS (P = 0.02) in follicular fluid were associated with a failure to become pregnant after embryo transfer. IgG antibodies in sera and follicular fluid and IgA antibodies in sera were unrelated to IVF outcome. Similarly only anti-MOMP IgA (P = 0.02) and anti-rLPS IgA (P = 0.04) in follicular fluid were correlated with human hsp 60 expression in follicular fluid. The unique association between IgA antibodies to two chlamydial antigens in follicular fluid and both hsp 60 expression and IVF failure provides further support for the possibility that a persistent upper genital tract chlamydial infection contributes to IVF failure in some women.

背景与目标： 最近的证据表明，沙眼衣原体可以在女性上生殖道中以不可培养的状态持续存在。由于未经怀疑的沙眼衣原体感染与不良的体外受精 (IVF) 结果有关，因此我们试图在接受IVF的妇女的生殖道中进一步发现沙眼衣原体的证据。检查了成对的卵泡液和接受IVF的妇女血清中沙眼衣原体主要结构蛋白的抗体的患病率和分布。对来自149名妇女的血清和卵泡液样品进行了免疫球蛋白 (Ig)G和IgA抗体的检测，该抗体针对两种沙眼衣原体抗原，主要外膜蛋白 (MOMP) 和重组脂多糖 (rLPS) 片段。此外，测定了人60 kDa热休克蛋白 (hsp 60) 在卵泡液中的表达。通过聚合酶链反应，连接酶链反应和DNA探针，所有宫颈和卵泡液样品均阴性沙眼衣原体。来自60% 名受试者的血清中抗衣原体rLPS IgG阳性; 36% 抗MOMP IgG阳性。同样，分别在34和14% 名受试者的血清中检测到rLPS导向和MOMP导向的IgA。分别在42和41% 的卵泡液中检测到针对MOMP和rLPS的IgG抗体。在卵泡液8.7% 中鉴定出抗MOMP IgA，而27.5% 对抗rLPS呈阳性igA。人类hsp 60的表达在测试的卵泡液11.6% 中被记录。卵泡液中MOMP (P = 0.03) 和rlp (P = 0.02) 的IgA抗体与胚胎移植后未能怀孕有关。血清和卵泡液中的IgG抗体和血清中的IgA抗体与IVF结果无关。同样，只有卵泡液中的抗MOMP IgA (P = 0.02) 和抗rLPS IgA (P = 0.04) 与人hsp 60在卵泡液中的表达相关。针对两种衣原体抗原的IgA抗体与hsp 60表达和IVF失败为某些女性持续的上生殖道衣原体感染导致IVF失败的可能性提供了进一步的支持。

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: :Assisted conception providers in England were surveyed to establish the uptake of NICE guideline for infertility particularly in respect of assisted conception and the criteria used to accept patients for NHS funded treatment. Detailed information on selection criteria was obtained from a group of commissioning consortia at an advanced stage in their arrangements. While there was an overall increase in the number of NHS IVF cycles purchased in England, implementation is stalled at one fresh cycle in the vast majority of Primary Care Trusts (PCTs). There is little consensus about the criteria used for acceptance into an NHS programme. This is particularly so in respect of social criteria which are often arbitrary and used as a rationing tool. This information complements that provided by the survey of Primary Care Trusts performed in March 2005 by the All Party Parliamentary Group on Infertility (APPGI) in partnership with the National Infertility Awareness Campaign (NIAC) which together provide a basis for recommendations for NHS funding. The recommendations presented should be applied across England and Wales to ensure consistency, fairness and equity of access.

背景与目标： : 对英格兰的辅助受孕提供者进行了调查，以建立对不孕症的NICE指南，特别是在辅助受孕和接受NHS资助治疗的患者的标准方面。有关选择标准的详细信息是从一组委托财团在其安排的高级阶段获得的。虽然在英格兰购买的NHS IVF周期数量总体上有所增加，但在绝大多数初级保健信托基金 (pct) 中，实施停滞在一个新的周期。关于接受NHS计划的标准几乎没有共识。在社会标准方面尤其如此，这些标准通常是任意的，并被用作配给工具。该信息补充了由全党议会不孕症小组 (APPGI) 与全国不孕症意识运动 (NIAC) 合作在2005年3月进行的初级保健信托调查所提供的信息，该调查共同为NHS资金建议提供了基础。提出的建议应适用于英格兰和威尔士，以确保访问的一致性，公平性和公平性。

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: 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: 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: 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: :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： : 我们的目标是使用非侵入性高分辨率 (117x70 microm) 磁共振 (microMRI) 和视觉系统诱发电位 (VEP) 技术，跟踪畸形疾病的过程，然后在转基因小鼠中进行部分恢复。我们使用了JOE (用于J37 golli过表达) 转基因小鼠，该小鼠经过工程改造以过表达golli J37，Golli-mbp基因复合物的产物，特别是在少突胶质细胞中。从21天到75天大，在11.7 T扫描仪上使用非侵入性体内vep和3D T2-weighted显微mri跟踪了JOE transgenics及其未受影响的兄弟姐妹，我们认为这是同类研究中的首次纵向研究。microMRI数据表明，在髓鞘形成峰值期间 (21-42天)，明显的整体髓鞘减少，与对照组相比，JOE小鼠在以后的年龄 (>60天) 得到了部分纠正。这些显微mri数据与 [Campagnoni在 (1995) “髓鞘形成的分子生物学” 处有很好的相关性。见: Ransom B，Kettenmann H (eds) 神经胶质-一篇论文。牛津大学出版社，伦敦，第555-570页] 髓磷脂染色，[Campagnoni AT，macklin WB (1988) 髓鞘蛋白基因表达的细胞和分子方面。Mol Neurobiol 2:41-89] 在髓鞘形成的高峰期短暂的意图震颤，在以后的年龄减弱，并且 [Lees MB，Brostoff SW (1984) 蛋白在髓鞘中: 莫雷尔 (ed) 髓鞘。纽约和伦敦的万普宁出版社，第197-224页] VEPs，所有这些都表明乔小鼠中枢神经系统髓鞘发育和持续的低髓鞘作用显著延迟。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延迟的小鼠大脑中髓鞘形成的增加。

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病毒，人细小病毒B19，水痘病毒病毒和怀孕期间发生的风疹病毒病毒，用于诊断和管理复古病毒感染 (HIV和HTLV) 和肝炎 (HBV和HCV)，乳头瘤病毒分型，并检测病毒与临床表现 (心肌病或胰岛素依赖型糖尿病与柯萨奇病毒B: 卡波西氏肉瘤与HHV 8) 或调查病毒es的环境污染。这些定性和定量的新分子标记物代表了病毒诊断研究领域，感染过程中病毒载量的监测，病毒性疾病的治疗控制以及病毒传播流行病学领域的重要进展。使用可用的商业试剂和试剂盒可获得标准化和自动化。

BACKGROUND & AIMS: :Severe preeclampsia rarely occurs prior to 20 weeks of gestation except in pregnancies with triploidy. The patient reported herein is a 29-year-old primigravida who developed severe preeclampsia at 20 weeks of gestation. Evaluation of the pregnancy demonstrated a markedly abnormal quadruple screen. Amniocentesis demonstrated a fetus with triploidy, despite a normal appearance.

背景与目标： : 除三倍体妊娠外，妊娠20周前很少发生严重的先兆子痫。本文报道的患者是一名29岁的初产妇，在妊娠20周时出现严重的先兆子痫。对妊娠的评估显示出明显异常的四重筛查。羊膜穿刺术显示胎儿具有三倍体，尽管外观正常。

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 (MMPs) 由于其在肿瘤转移以及退行性疾病 (如骨关节炎和类风湿性关节炎) 的兴起和传播中的作用而成为深入研究的主题。初步设计了140类药物小分子基质metalloproteinase-3抑制剂，作为优化和合成的起始支架，使用一系列高度预测性的三维定量构效关系模型，包括比较分子场分析和比较分子相似性指数分析，对接和得分。沙利度胺被选为新铅系列的骨架，因为它适度抑制MMP-3，具有抗血管生成作用，并且易于进行结构修饰。根据辛醇-水分配系数ClogP估计，大多数新化合物表现出中等至高的预测生物活性和良好的生物利用度。化合物102尤其表现出对MMP-3极其有利的预测活性; 具有适度的生物利用度; 满足Lipinski的五法则; 并显示出有望进一步优化，合成和实验评估作为潜在的辅助抗癌或抗风湿治疗剂。

BACKGROUND & AIMS: :Six different secretory proteins of molecular weights (15, 26, 30, 41, 55 and 70 kDa) were isolated from 8-day-old culture filtrate of Mycobacterium tuberculosis H37Ra using different column chromatography techniques. These proteins were further examined for their ability to induce cell mediated (T-cell proliferation assay) and humoral immune response (ELISA) in mice immunized with total culture filtrate proteins. Out of six proteins, three proteins showed good reactivity. However, the activity was at a maximum with 30 kDa antigen. The immune response induced by 30 kDa antigen emulsified in Freund's incomplete adjuvant (FIA) was investigated and was found to be dose dependent. The T-cell response induced by this protein was skewed towards T-helper (Th1) cells as determined by the pronounced secretion of interleukin-2 (IL-2) and gamma-interferon (IFN-gamma). The protective activity of the 30 kDa protein was also evaluated and compared with reference to Bacillus Calmette Guerin (BCG) vaccine in the mice challenged with virulent M. tuberculosis H37Rv. The degree of protection afforded by the 30 kDa antigen on the basis of mortality and the significant decrease in c.f.u.'s recovered from different organs (lung, liver, spleen) after 30 days of challenge with LD50 of M. tuberculosis H37Rv was significantly higher in comparison to BCG vaccinated animals. However, the degree of immunity induced by this antigen decreased with time (when challenged 8 and 12 weeks post-immunization) but it was still comparable with BCG. These findings suggest that 30 kDa secretory protein of M. tuberculosis is the key immunoprotective antigen and may be a suitable candidate for the development of an alternative subunit vaccine against tuberculosis.

背景与目标： : 使用不同的柱色谱技术从8天大的结核分枝杆菌H37Ra培养滤液中分离出六种分子量不同的分泌蛋白 (15、26、30、41、55和70 kDa)。进一步检查了这些蛋白质在用总培养滤液蛋白免疫的小鼠中诱导细胞介导的 (T细胞增殖测定) 和体液免疫反应 (ELISA) 的能力。在六种蛋白质中，三种蛋白质显示出良好的反应性。然而，30 kDa抗原的活性最大。研究了在弗氏不完全佐剂 (FIA) 中乳化的30 kDa抗原诱导的免疫反应，并发现其具有剂量依赖性。由该蛋白诱导的T细胞反应向T辅助 (Th1) 细胞倾斜，这是由interleukin-2 (IL-2) 和 γ-干扰素 (IFN-γ) 的明显分泌决定的。还评估了30 kDa蛋白的保护活性，并将其与卡介苗 (BCG) 疫苗进行了比较，该疫苗在用强毒力结核分枝杆菌H37Rv攻击的小鼠中进行了比较。30 kDa抗原在死亡率的基础上提供的保护程度，以及在用结核分枝杆菌H37Rv的LD50攻击30天后从不同器官 (肺，肝，脾) 恢复的c.f.u.的显着降低与BCG接种的动物相比更高。然而，该抗原诱导的免疫程度随时间而降低 (预防接种后8周和12周受到攻击时)，但仍与BCG相当。这些发现表明，结核分枝杆菌的30 kDa分泌蛋白是关键的免疫保护性抗原，并且可能是开发针对结核病的替代亚单位疫苗的合适候选者。

BACKGROUND & AIMS: :We have constructed a physical map of a > 2-Mb region on mouse chromosome 6 that contains the natural killer gene complex (NKC). The map comprises a contig of 14 overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers. NKC genetically linked genes encode > 17 proteins that directly control innate NK cell-mediated tumor lysis and disease resistance. Herein we show that Nkrp1 genes are clustered in a region flanked by A2m and Cd69 genes and that most Ly49 genes are clustered in a distal region -1 Mb distant. Importantly, syntenic intervals of mouse chromosome 6 and human chromosome 12p that include the NKC are conserved. NKC species conservation suggests that the human NKC may contain orthologues for the mouse viral disease resistance genes, Cmv1 and Rmp1. The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens.

背景与目标： : 我们已经在小鼠6号染色体上构建了一个> 2-Mb区域的物理图，其中包含自然杀伤基因复合物 (NKC)。该图谱包含14个重叠的酵母人工染色体的重叠群，我们在其上定位了25个NKC标记。NKC基因连接的基因编码> 17种直接控制先天NK细胞介导的肿瘤溶解和抗病的蛋白质。在本文中，我们显示Nkrp1基因聚集在A2m和Cd69基因两侧的区域中，并且大多数Ly49基因聚集在远端区域-1 Mb远处。重要的是，包含NKC的小鼠6号染色体和人类12p染色体的同义间隔是保守的。NKC物种保护表明，人类NKC可能包含小鼠病毒抗病基因Cmv1和rmp1的直系同源物。高分辨率NKC图谱将有助于NKC基因调控的研究和表型定义的基因产物的鉴定，这些基因产物赋予NK细胞针对病毒病原体的防御能力。