• 【选择性剖宫产后的新生儿死亡率和发病率与常规预期管理的关系:一项决策分析。】 复制标题 收藏 收藏
    DOI:10.1053/j.semperi.2006.07.010 复制DOI
    作者列表:Signore C,Hemachandra A,Klebanoff M
    BACKGROUND & AIMS: :A number of competing risks and benefits influence the rates of neonatal morbidity and mortality in elective cesarean delivery versus expectant management. To compare these rates, we developed complex decision trees to model the expected outcomes among hypothetical cohorts of 1,000,000 uncomplicated pregnancies undergoing elective cesarean delivery versus 1,000,000 comparable pregnancies undergoing routine pregnancy management. A separate tree was created for each complication, including neonatal death, respiratory morbidity, intracranial hemorrhage, and brachial plexus injury. We found that neonatal mortality was increased among elective cesarean deliveries, but perinatal mortality was higher with routine expectant management due to fetal deaths. Respiratory morbidity was substantially more common among infants delivered by elective cesarean delivery, whereas intracranial hemorrhage and brachial plexus injury were less common. We conclude that the fetal/neonatal impact of elective cesarean is mixed, but any improvement in perinatal health is likely to be small.
    背景与目标: :许多竞争性风险和收益影响选择性剖宫产与预期管理方式下新生儿发病率和死亡率的比率。为了比较这些比率,我们开发了复杂的决策树以对假设的队列中的预期结果进行建模,这些假设队列中有1,000,000例进行了选择性剖宫产的未合并妊娠与1,000,000例进行了常规妊娠管理的可比较的妊娠。为每种并发症创建一棵单独的树,包括新生儿死亡,呼吸系统疾病,颅内出血和臂丛神经损伤。我们发现,选择性剖宫产分娩的新生儿死亡率增加,但由于胎儿死亡,常规的常规处理导致围产期死亡率更高。择期剖宫产分娩的婴儿中呼吸系统疾病的发病率更为普遍,而颅内出血和臂丛神经损伤的情况则较不常见。我们得出结论,选择性剖宫产对胎儿/新生儿的影响是混合的,但是围产期健康的任何改善都可能很小。
  • 【角膜的基质形态发生是由GlcNAc 6-O-磺基转移酶对硫酸角质素的修饰介导的。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.0605441103 复制DOI
    作者列表:Hayashida Y,Akama TO,Beecher N,Lewis P,Young RD,Meek KM,Kerr B,Hughes CE,Caterson B,Tanigami A,Nakayama J,Fukada MN,Tano Y,Nishida K,Quantock AJ
    BACKGROUND & AIMS: :Matrix assembly and homeostasis in collagen-rich tissues are mediated by interactions with proteoglycans (PGs) substituted with sulfated glycosaminoglycans (GAGs). The major GAG in cornea is keratan sulfate (KS), which is N-linked to one of three PG core proteins. To ascertain the importance of the carbohydrate chain sulfation step in KS functionality, we generated a strain of mice with a targeted gene deletion in Chst5, which encodes an N-acetylglucosamine-6-O-sulfotransferase that is integral to the sulfation of KS chains. Corneas of homozygous mutants were significantly thinner than those of WT or heterozygous mice. They lacked high-sulfated KS, but contained the core protein of the major corneal KSPG, lumican. Histochemically stained KSPGs coassociated with fibrillar collagen in WT corneas, but were not identified in the Chst5-null tissue. Conversely, abnormally large chondroitin sulfate/dermatan sulfate PG complexes were abundant throughout the Chst5-deficient cornea, indicating an alteration of controlled PG production in the mutant cornea. The corneal stroma of the Chst5-null mouse exhibited widespread structural alterations in collagen fibrillar architecture, including decreased interfibrillar spacing and a more spatially disorganized collagen array. The enzymatic sulfation of KS GAG chains is thus identified as a key requirement for PG biosynthesis and collagen matrix organization.
    背景与目标: :胶原蛋白丰富的组织中的基质组装和体内平衡是通过与被硫酸化的糖胺聚糖(GAG)取代的蛋白聚糖(PG)的相互作用而介导的。角膜中的主要GAG是硫酸角质素(KS),它与三种PG核心蛋白之一进行N-连接。为了确定碳水化合物链硫酸化步骤在KS功能中的重要性,我们生成了在Chst5中具有靶向基因缺失的小鼠品系,该菌株编码了KS链硫酸化所必需的N-乙酰氨基葡萄糖-6-O-磺基转移酶。纯合突变体的角膜明显比野生型或杂合小鼠的角膜薄。他们缺乏高硫酸盐化的KS,但含有主要角膜KSPG的核心蛋白lumican。组织化学染色的KSPG与野生型角膜中的原纤维胶原蛋白相关联,但在Chst5无组织中未发现。相反,在整个Chst5缺陷型角膜中,异常大的硫酸软骨素/硫酸皮肤素PG复合物丰富,表明突变体角膜中受控PG产生的改变。 Chst5-null小鼠的角膜基质在胶原纤维结构中表现出广泛的结构变化,包括减小的纤维间间距和空间上更混乱的胶原阵列。因此,KS GAG链的酶促硫酸化被确定为PG生物合成和胶原基质组织的关键要求。
  • 【通过基质辅助激光解吸/电离飞行时间质谱测定人呼吸道合胞病毒附着(G)蛋白的二硫键排列。】 复制标题 收藏 收藏
    DOI:10.1002/pro.5560060619 复制DOI
    作者列表:Gorman JJ,Ferguson BL,Speelman D,Mills J
    BACKGROUND & AIMS: The attachment protein or G protein of the A2 strain of human respiratory syncytial virus (RSV) was digested with trypsin and the resultant peptides separated by reverse-phase high-performance liquid chromatography (HPLC). One tryptic peptide produced a mass by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) corresponding to residues 152-187 with the four Cys residues of the ectodomain (residues 173, 176, 182, and 186) in disulfide linkage and absence of glycosylation. Sub-digestion of this tryptic peptide with pepsin and thermolysin produced peptides consistent with disulfide bonds between Cys173 and Cys186 and between Cys176 and Cys182. Analysis of ions produced by post-source decay of a peptic peptide during MALDI-TOF-MS revealed fragmentation of peptide bonds with minimal fission of an inter-chain disulfide bond. Ions produced by this unprecedented MALDI-induced post-source fragmentation corroborated the existence of the disulfide arrangement deduced from mass analysis of proteolysis products. These findings indicate that the ectodomain of the G protein has a non-glycosylated subdomain containing a "cystine noose."

    背景与目标: 用胰蛋白酶消化人呼吸道合胞病毒(RSV)A2株的附着蛋白或G蛋白,并通过反相高效液相色谱(HPLC)分离得到的肽。一种胰蛋白酶肽通过基质辅助激光解吸/电离(MALDI)飞行时间(TOF)质谱(MS)产生质量,对应于带有胞外域的四个Cys残基的残基152-187(残基173、176, 182和186)中的二硫键和不存在糖基化作用。用胃蛋白酶和嗜热菌蛋白酶亚消化该胰蛋白酶消化的肽产生的肽与Cys173和Cys186之间以及Cys176和Cys182之间的二硫键一致。对在MALDI-TOF-MS过程中由消化性肽的源后衰减产生的离子进行的分析显示,肽键断裂且链间二硫键的裂变最小。由这种前所未有的MALDI诱导的源后裂解产生的离子证实了从蛋白水解产物的质量分析推导出的二硫键结构的存在。这些发现表明,G蛋白的胞外域具有一个非糖基化的亚域,其中包含一个“胱氨酸套索”。

  • 【单相抑郁症的文献治疗:一项荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1016/s0005-7916(97)00005-0 复制DOI
    作者列表:Cuijpers P
    BACKGROUND & AIMS: In the last decades, several therapies for unipolar depression have been developed, for example cognitive therapy, behavior therapy and pharmacotherapy. A new kind of therapy is bibliotherapy. What is new in this treatment modality is not the content, because bibliotherapy usually uses a cognitive-behavioral approach. Only the form in which it is presented is new. In bibliotherapy the patient takes a standardized treatment home, in book form, and works it through more or less independently. Contacts with therapists are only supportive or facilitative. No traditional relationship between therapist and patient is developed. In this article the relevance of bibliotherapy for the clinical practice is presented and a meta-analysis of the research into bibliotherapy is described.

    背景与目标: 在最近的几十年中,已经开发出几种用于单相抑郁的疗法,例如认知疗法,行为疗法和药物疗法。一种新的疗法是参考疗法。这种治疗方式的新内容不是内容,因为书目疗法通常使用认知行为方法。仅显示它的形式是新的。在书目治疗中,患者以书本形式接受标准化治疗,并或多或少地独立进行治疗。与治疗师的联系仅是支持性的或促进性的。在治疗师和患者之间没有建立传统的关系。本文介绍了参考书目疗法与临床实践的相关性,并描述了参考书目疗法研究的荟萃分析。

  • 【右精索静脉曲张和缺氧,是男性不育症的关键因素:睾丸引流系统受损的流体力学分析。】 复制标题 收藏 收藏
    DOI:10.1016/s1472-6483(10)60638-4 复制DOI
    作者列表:Gat Y,Gornish M,Navon U,Chakraborty J,Bachar GN,Ben-Shlomo I
    BACKGROUND & AIMS: :Varicocele is considered a predominantly unilateral left-sided disease. However, since male fertility is preserved with only one healthy testis, infertility perforce represents bilateral testicular dysfunction. It was hypothesized that: (i) right varicocele cannot be diagnosed by palpation and therefore has not been treated in the past by the traditional treatment, and (ii) right varicocele causes impaired oxygen supply in the right testicular microcirculation, leading to germ cell degeneration. This study performed venographies of both right and left internal spermatic veins during the treatment of 840 infertile men with varicocele and analysed the results using tools of fluid mechanics. Histopathology of the right testis revealed stagnation of blood flow and degenerative changes attributed to lack of adequate oxygenation in all testicular cell types. Right varicocele was found in the vast majority of the patients. We found that due to the destruction of one-way valves, pathologic hydrostatic pressure is produced in the testicular venous microcirculatory system about five times higher than normal, exceeding arteriolar pressure. The pressure gradient between the arterioles and venules in the testicular tissue is therefore reversed, leading to persistent hypoxia. Right varicocele, although undetected, is prevalent in infertile men with varicocele, hence only bilateral occlusion of the internal spermatic veins, including the associated bypasses, eliminating the pathologic hydrostatic pressure will lead to resumption of arterial blood flow in the testicular microcirculation.
    背景与目标: :精索静脉曲张被认为是主要的单侧左侧疾病。但是,由于只有一个健康的睾丸才能维持男性的生育能力,因此不育症的强迫表现为双侧睾丸功能障碍。假设:(i)右精索静脉曲张不能通过触诊诊断,因此过去没有用传统疗法治疗;(ii)右精索静脉曲张导致右睾丸微循环中的氧气供应受损,导致生殖细胞变性。这项研究在治疗840名不育男性精索静脉曲张的过程中对左右两侧的精索静脉进行了静脉造影,并使用流体力学工具对结果进行了分析。右睾丸的组织病理学显示血流停滞和变性变化归因于所有睾丸细胞类型缺乏足够的氧合。在绝大多数患者中发现了右精索静脉曲张。我们发现由于单向阀的破坏,睾丸静脉微循环系统中产生的病理性静水压力比正常高约五倍,超过了小动脉压力。因此,睾丸组织中小动脉和小静脉之间的压力梯度会反向,从而导致持续的缺氧。右精索静脉曲张虽然未被发现,但在精索静脉曲张的不育男性中很普遍,因此,只有双侧内精子静脉闭塞,包括相关的旁路,消除病理性静水压会导致睾丸微循环中动脉血流的恢复。
  • 【拉坦前列素对人小梁网细胞中基质金属蛋白酶及其组织抑制剂表达的影响。】 复制标题 收藏 收藏
    DOI:10.1167/iovs.06-0036 复制DOI
    作者列表:Oh DJ,Martin JL,Williams AJ,Russell P,Birk DE,Rhee DJ
    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: 目的:确定拉坦前列素对小梁网(TM)中人基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)表达的影响。
    方法:分离总RNA,进行定性RT-PCR检测人TM组织和TM内皮细胞外植体培养物中MMP和TIMP的mRNA。用媒介物对照或拉坦前列素酸处理TM细胞的培养物24小时。对来自五个不同供体的细胞培养物进行了实时RT-PCR,以确定表达的相对变化。 GAPDH用作内源性对照。
    结果:MMP-1,-2,-3,-11,-12,-14,-15,-16,-17,-19和-24和TIMP-1至-4的mRNA均存在于TM组织和TM细胞培养物。找不到MMP-9。在对照TM内皮细胞中,MMP mRNA的相对表达为MMP-2和-14> MMP-16,-19和-24> MMP-15> MMP-11和-17> MMP-1和-3> MMP -12。 TIMP mRNA的相对表达为TIMP-1> TIMP-2和-3> TIMP-4。拉坦前列素可提高MMP-1(在五种文化中的四种),MMP-3(在五种文化中的四种),MMP-17(在五种文化中的三种),MMP-24(在五种文化中),TIMP-2,- 3和-4表达(在五种文化中的三种); MMP-11和-15下调。
    结论:与预期结果相反,拉坦前列素似乎对TM细胞有显着影响。拉坦前列素处理可增加MMP-1,-3,-17和-24基因的转录。 TIMP-2,-3和-4也被上调。这些TIMP的上调可以补偿那些MMP的增加。 MMP-9的缺乏和大量TIMP的同时上调可能解释了拉坦前列素对TM外流的作用有限。
  • 【大鼠角膜缘和中央角膜上皮中基因表达(SAGE)的系列分析。】 复制标题 收藏 收藏
    DOI:10.1167/iovs.06-0216 复制DOI
    作者列表:Adachi W,Ulanovsky H,Li Y,Norman B,Davis J,Piatigorsky J
    BACKGROUND & AIMS: PURPOSE:To identify genes preferentially expressed in the stem-cell-rich limbal epithelium of the rat cornea. METHODS:The limbal and central corneal epithelial cells of 6-week-old rats were isolated by microdissection. Serial analysis of gene expression (SAGE) libraries were constructed and analyzed, and in situ hybridization, reverse transcription-polymerase chain reaction (RT-PCR) and cDNA cloning were conducted by conventional procedures. RESULTS:The rat limbal and central corneal epithelial SAGE libraries consisted of 41,894 and 40,691 tags, respectively. After annotation, this was reduced to 759 transcripts specific for the limbal library and 844 transcripts specific for the central corneal library; 2292 transcripts overlapped. Transcripts encoding proteins with metabolic functions comprised the major functional category in both libraries. In situ hybridization and/or RT-PCR results of 12 of the most abundant, highly enriched transcripts in the limbal epithelium were in general agreement with the SAGE data and showed that these proteins are also expressed in the conjunctival epithelium. Interesting limbal-enriched transcripts encode WDNM1-like protein (similar to WDNM1/Expi, a putative secreted proteinase and inhibitor of metastasis), mesothelin (a cancer marker), marapsin (a trypsin-like serine protease that may control cell growth and migration), K4 and K15 (both cytokeratins), and membrane-spanning four-domain subfamily A member 8B. WDNM1-like protein was cloned and confirmed as a member of the four-disulfide core family. CONCLUSIONS:The SAGE results extend the database of genes expressed in the rodent cornea and suggest an association between several genes preferentially expressed in the limbal epithelium with cellular proliferation and migration.
    背景与目标: 目的:鉴定在大鼠角膜的富含干细胞的角膜缘上皮细胞中优先表达的基因。
    方法:采用显微解剖技术分离6周龄大鼠角膜缘和角膜上皮细胞。构建并分析基因表达(SAGE)库的序列分析,并通过常规方法进行原位杂交,逆转录-聚合酶链反应(RT-PCR)和cDNA克隆。
    结果:大鼠角膜缘和角膜上皮SAGE文库分别由41,894和40,691个标签组成。注释后,该数目减少为角膜缘文库特异的759个转录物和中央角膜文库特异的844个转录物。 2292个成绩单重叠。编码具有代谢功能的蛋白质的转录本在两个文库中均属于主要功能类别。角膜缘上皮细胞中12种最丰富,高度富集的转录本的原位杂交和/或RT-PCR结果与SAGE数据基本一致,表明这些蛋白也在结膜上皮细胞中表达。有趣的角膜缘丰富的转录本编码WDNM1样蛋白(类似于WDNM1 / Expi,一种推测的分泌蛋白酶和转移抑制剂),间皮素(一种癌症标志物),marapsin(一种胰蛋白酶样丝氨酸蛋白酶,可以控制细胞的生长和迁移)。 ,K4和K15(均为细胞角蛋白)和跨膜四结构域亚家族A成员8B。克隆了类似WDNM1的蛋白质,并确认其为四-二硫键核心家族的成员。
    结论:SAGE结果扩展了在啮齿动物角膜中表达的基因数据库,并暗示了在角膜缘上皮中优先表达的几个基因与细胞增殖和迁移之间的关联。
  • 【艾滋病患者的更昔洛韦耐药性巨细胞病毒(CMV)视网膜炎一例:CMV病毒载量和血室中病毒突变的纵向分子分析。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:1997-06-01
    来源期刊:AIDS
    DOI:10.1097/00002030-199707000-00005 复制DOI
    作者列表:Boivin G,Gilbert C,Morissette M,Handfield J,Goyette N,Bergeron MG
    BACKGROUND & AIMS: OBJECTIVE:To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis.

    METHODS:Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis.

    RESULTS:At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay.

    CONCLUSIONS:Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.

    背景与目标: 目标:研究巨细胞病毒耐药的巨细胞病毒性视网膜炎的艾滋病患者的巨细胞病毒(CMV)病毒载量与多形核白细胞(PMNL)和血浆样品中特定UL97突变之间的时间关系。

    方法:使用非分子方法和定量聚合酶链反应(PCR)分析了连续的PMNL和血浆样品,以测定CMV病毒载量。使用巢式PCR和限制性内切酶分析对相同样品中最引起更昔洛韦耐药的突变进行筛查。

    结果:在CMV视网膜炎进展时(6个月后) (更昔洛韦)的检测,在PMNL和血浆样品中均发现CMV DNA载量迅速增加。这种增加与在相同样品中出现特定突变(V594)以及对更昔洛韦耐药的血液分离株的回收率平行。然而,在该患者中,唯一可以预测CMV疾病进展的检测方法是使用PMNL进行定量PCR检测,而在较小程度上使用pp65抗原血症检测。

    结论:定量使用诸如PCR的敏感测定法评估PMNL中CMV病毒载量似乎是监测艾滋病患者抗病毒治疗的一种有前途的方法。此外,可以在PMNL和血浆样品中直接检测到更昔洛韦耐药的常见突变。

  • 【胃癌中pRb2 / p130,VEGF,EZH2,p53,p16(INK4A),p27(KIP1),p21(WAF1),Ki-67表达模式的免疫组织化学分析。】 复制标题 收藏 收藏
    DOI:10.1002/jcp.20833 复制DOI
    作者列表:Mattioli E,Vogiatzi P,Sun A,Abbadessa G,Angeloni G,D'Ugo D,Trani D,Gaughan JP,Vecchio FM,Cevenini G,Persiani R,Giordano A,Claudio PP
    BACKGROUND & AIMS: :Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.
    背景与目标: :尽管在对抗胃癌方面取得了长足的进步,但它仍然是由特殊的组织学和分子特征定义的复杂致死性疾病。本研究的目的是研究pRb2 / p130,VEGF,EZH2,p53,p16(INK4A),p27(KIP1),p21(WAF1),Ki-67的表达,并分析其与临床病理因素的可能关系。通过免疫组织化学方法对47例患者的表达模式进行了检查,其中27例为肠型,20例为弥漫型,平均随访56个月,并通过Western blot检测AGS,N87,KATO-III和YCC-2 ,-3,-16个胃细胞系。总体而言,胃癌显示EZH2与高水平的p53,Ki-67和细胞质pRb2 / p130相关(分别为P <0.05和P <0.01)。在肠型中发现EZH2表达增加,并且与远处转移的风险相关(分别为P <0.05和P <0.01),表明该蛋白可能在这种类型的癌症中具有预后价值。有趣的是,观察到p27(KIP1)表达水平与晚期疾病和转移的风险之间存在强烈的负相关(P <0.05),而p21(WAF1)和低度胃癌(G1)的表达水平之间呈正相关。肿瘤(P <0.05),证实了这些肿瘤抑制基因在胃癌中的传统接受作用。最后,在核pRb2 / p130的表达水平与低度(G1)胃肿瘤的表达水平之间发现了直接相关性,具有统计学意义(P <0.05)。总之,这些数据可能有助于进一步阐明与两种主要胃癌组织学类型及其侵袭潜能有关的致病机制。
  • 【葡萄膜炎患者肝素表面改性人工晶状体与常规聚甲基丙烯酸甲酯人工晶状体的回顾性分析。】 复制标题 收藏 收藏
    DOI:10.1007/BF02583275 复制DOI
    作者列表:Lardenoye CW,van der Lelij A,Berendschot TT,Rothova A
    BACKGROUND & AIMS: BACKGROUND:Several studies described the benefits of the heparin-surface-modified intraocular tens (HSM IOL) with regard to the reduced inflammation in routine extracapsular cataract extractions. However, limited information is available about the advantages of the HSM IOL in patients with an intraocular inflammation. AIM:To assess the eventual benefits of the HSM IOL compared to the regular polymethylmethacrylate intraocular lens (PMMA IOL) in patients with uveitis. METHODS:A retrospective study of 43 patients with uveitis of various origins who underwent an extracapsular cataract extraction (24 with HSM, 19 with PMMA IOL). The activity of intraocular inflammation, visual acuity, eventual complications, and medications were examined. Standardized follow-up dates were used (before surgery, one and fourteen days, five and eleven months after surgery.) RESULTS:No difference in the inflammatory, activity was noted between HSM and PMMA groups; neither at short term clinical evaluation, nor at five months after surgery. Despite a slightly better visual acuity in the HSM group before surgery, no long term differences were observed. After surgery the increase in visual acuity was similar for both groups, as well as the frequency of cystoid macular oedema (CMO) and synechiae. Fewer patients in HSM group required Nd:YAG posterior capsulotomy, but the difference was not significant. CONCLUSION:No clinical advantage was found when the HSM IOL was compared with the regular PMMA IOL in 43 patients with uveitis.
    背景与目标: 背景:多项研究描述了肝素表面修饰眼内张力(HSM IOL)在常规囊外白内障摘除术中减少炎症方面的益处。但是,关于眼内炎症患者中HSM IOL的优势的信息很少。
    目的:评估与常规聚甲基丙烯酸甲酯人工晶状体(PMMA IOL)相比,HSM IOL在葡萄膜炎患者中的最终益处。
    方法:回顾性研究43例不同来源葡萄膜炎患者的囊外白内障摘除术(HSM 24例,PMMA IOL 19例)。检查眼内炎症,视力,最终并发症和药物的活动。使用标准化的随访日期(手术前,手术后的第1天,第14天,手术后的第5个月和第11个月)。
    结果:HSM和PMMA组之间在炎症,活性方面没有差异;既不进行短期临床评估,也不在术后五个月进行评估。尽管术前HSM组的视敏度稍好,但未观察到长期差异。手术后,两组的视敏度增加,囊状黄斑水肿(CMO)和粘连的发生率相似。 HSM组需要Nd:YAG后囊切开术的患者较少,但差异无统计学意义。
    结论:将HSM IOL与常规PMMA IOL相比较在43例葡萄膜炎患者中未发现临床优势。
  • 【骨髓嵌合体小鼠的肿瘤浸润基质细胞的制备和功能分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1348-0421.2006.tb03830.x 复制DOI
    作者列表:Ishigaki H,Yamamoto Y,Ishida H,Kajino K,Itoh Y,Fujiyama Y,Ogasawara K
    BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.
    背景与目标: :肿瘤浸润基质细胞(TISC)以及肿瘤本身都被认为与肿瘤相关的免疫抑制有关,这是肿瘤逃避免疫监视的关键机制之一。然而,由于在已建立的肿瘤中TISC的比例很小,因此TISC的制备是困难的。因此,通常被认为与肿瘤相关的免疫抑制有关的细胞是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中,我们开发了一种从已建立的肿瘤中直接制备TISC的方法,以分析其功能。使用绿色荧光蛋白(GFP)转基因(Tg)小鼠和移植有GFPTg小鼠骨髓(BM)细胞的C57BL / 6小鼠,我们检测到TISC的三个亚群:一个与源自BM的未成熟髓样细胞(ImC)相容。其他两个亚群CD11b()细胞和CD11b(-)细胞并非源自BM。在存在GM-CSF的情况下与肿瘤培养后,TISC包括这些亚群,但并非每个亚群独立地抑制由抗CD3诱导的T细胞增殖。在我们的系统中,肿瘤并未直接抑制T细胞反应,但来自肿瘤的未知因素影响了TISC的免疫抑制。
  • 【改良的摆锤装置的生物力学-力系统的理论考虑和体外分析。】 复制标题 收藏 收藏
    DOI:10.1093/ejo/cjl028 复制DOI
    作者列表:Kinzinger GS,Diedrich PR
    BACKGROUND & AIMS: :The aim of this study was to analyse the acting forces and moments induced by a special orthodontic appliance, the Pendulum K, for molar distalization in the transverse and sagittal planes. The purpose-designed test set-up (artificial maxilla with anchorage unit and two electrothermodynamic molars, an electronic measuring unit, a unit with force-moment sensor, an analogue/digital converter, and a data read-out unit) allowed simulation of in vivo conditions on the one hand and precise determination of the force systems on the other. The appliances investigated were three specimens of the Pendulum K. In vitro measurement of the resulting force systems revealed that the forces and moments in the transverse and sagittal planes remained almost constant over a 3 mm measuring increment when the distal screw was continuously activated (10 activations/mm). Without reactivation of the incorporated distal screw, however, a marked decline in the force systems was recorded. The Pendulum K allows translatory distalization of the upper molars and thus dental arch expansion, dispensing with the need for permanent teeth to be extracted, subject to a corresponding indication. This is achieved by continuous adjustment of an incorporated distal screw and by specific pre-activations of the Pendulum springs.
    背景与目标: :这项研究的目的是分析由特殊的正畸矫治器Pendulum K引起的作用力和力矩,以在横断面和矢状面上进行磨牙远侧。专门设计的测试装置(带有锚固单元和两个电热磨牙的人工上颌,一个电子测量单元,一个带有力矩传感器的单元,一个模拟/数字转换器和一个数据读出单元)允许模拟一方面是体内条件,另一方面是精确确定力系统。所研究的器具是Pendulum K的三个标本。对最终产生的力系统进行的体外测量显示,当连续激活远端螺钉(10次激活)时,横向和矢状面的力和力矩在3 mm的测量增量内几乎保持恒定。 /毫米)。然而,在没有重新激活所结合的远端螺钉的情况下,记录了力系统的显着下降。摆K允许上颌臼齿的平移远侧移动,从而使牙弓扩张,并在需要相应指示的情况下无需拔出恒牙。这是通过不断调整内置的远端螺钉并通过对摆弹簧进行特定的预激活来实现的。
  • 【多发性骨髓瘤中热休克蛋白90(HSP90)的表达和HSP90抑制剂(17-AAG)的作用分析。】 复制标题 收藏 收藏
    DOI:10.1080/10428190500472123 复制DOI
    作者列表:Duus J,Bahar HI,Venkataraman G,Ozpuyan F,Izban KF,Al-Masri H,Maududi T,Toor A,Alkan S
    BACKGROUND & AIMS: :Heat shock protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated an antitumor effect in solid tumors. To test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analysed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55% also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins and akt in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-XL, MCL-1 and akt. Furthermore, although a low concentration of bortezomib resulted in no cell death, a combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.
    背景与目标: :热休克蛋白90(HSP90)是结构折叠和维持各种蛋白质(包括与细胞信号相关的几种蛋白质)构象完整性的必需。利用HSP90抑制剂17-烯丙基氨基-17-去甲氧基格尔德霉素(17-AAG)的最新研究表明,在实体瘤中具有抗肿瘤作用。为了测试HSP90是否可以靶向于多发性骨髓瘤(MM)患者,我们首先通过免疫荧光和流式细胞术分析了骨髓瘤细胞系(U266)和原发性骨髓瘤细胞中HSP90的表达。在证明HSP90在骨髓瘤细胞中表达后,通过免疫过氧化物酶染色分析了32例MM患者的档案样本。在所有患者中,骨髓瘤细胞在所有样品中均表现出强烈的HSP90细胞质表达,并且55%的患者还表现出并发的核免疫阳性。与未处理的对照细胞相比,用17AAG处理U266细胞和原代MM细胞可导致凋亡明显增加。分析与17-AAG孵育的MM细胞中的抗凋亡BCL2家族蛋白和akt,表明BCL-2,BCL-XL,MCL-1和akt下调。此外,尽管低浓度的硼替佐米不会导致细胞死亡,但是17AAG和硼替佐米治疗的组合显示出对U266细胞系的协同凋亡作用。这些数据表明,针对HSP90的靶向抑制可能被证明是开发MM患者未来治疗选择的有效且创新的策略。
  • 【槲寄生制剂(伊斯卡多)在三维胶原蛋白基质系统中诱导T淋巴细胞运动的供体依赖性和剂量依赖性变异。】 复制标题 收藏 收藏
    DOI:10.1097/00001813-199704001-00014 复制DOI
    作者列表:Nikolai G,Friedl P,Werner M,Zänker KS
    BACKGROUND & AIMS: :Controlled activation of non-specific and specific immune defence mechanisms can beneficially manipulate the host's ability to attack malignant cells. In this context, migration and tissue distribution of immunocompetent cells may be prerequisites for an efficient immune surveillance. The effect of various non-cytotoxic concentrations of the Viscum album L. (mistletoe) preparation Iscadore QuFrF on the locomotory activity of immunomagnetically isolated human CD4+ and CD8+ T lymphocytes from healthy donors was investigated. Cellular migration was examined within a three-dimensional collagen matrix. Donor-dependent variations in baseline activities of spontaneously locomoting T cells were accompanied by individual response patterns of T cells from different donors in the presence of various concentrations of mistletoe preparation (0.25-2.5 micrograms/ml). Using the three-dimensional collagen matrix assay an induction of locomotory activity was detected in a highly reproducible fashion although the optimal concentration of mistletoe preparation and the time point of maximal response were individual for each donor. Our data suggest that the direct stimulation of T-cell migration by mistletoe components may modulate the system of immune surveillance and recognition in patients under mistletoe therapy.
    背景与目标: :非特异性和特异性免疫防御机制的受控激活可以有益地控制宿主攻击恶性细胞的能力。在这种情况下,免疫活性细胞的迁移和组织分布可能是有效免疫监视的先决条件。研究了Viscum album L.(槲寄生)制剂Iscadore QuFrF的各种非细胞毒性浓度对来自健康供体的免疫磁性分离的人CD4和CD8 T淋巴细胞运动功能的影响。在三维胶原蛋白基质中检查了细胞迁移。在各种浓度的槲寄生制剂(0.25-2.5微克/毫升)存在下,自发性自发性T细胞基线活动的供体依赖性变异伴随着来自不同供体的T细胞的个体反应模式。使用三维胶原蛋白基质测定法,以高度可重复的方式检测了运动活性的诱导,尽管对于每个供体而言,槲寄生制剂的最佳浓度和最大响应的时间点各不相同。我们的数据表明,槲寄生成分直接刺激T细胞迁移可能会调节槲寄生治疗下患者的免疫监视和识别系统。
  • 【卫生干预措施的优先重点设定:需要进行多标准决策分析。】 复制标题 收藏 收藏
    DOI:10.1186/1478-7547-4-14 复制DOI
    作者列表:Baltussen R,Niessen L
    BACKGROUND & AIMS: :Priority setting of health interventions is often ad-hoc and resources are not used to an optimal extent. Underlying problem is that multiple criteria play a role and decisions are complex. Interventions may be chosen to maximize general population health, to reduce health inequalities of disadvantaged or vulnerable groups, ad/or to respond to life-threatening situations, all with respect to practical and budgetary constraints. This is the type of problem that policy makers are typically bad at solving rationally, unaided. They tend to use heuristic or intuitive approaches to simplify complexity, and in the process, important information is ignored. Next, policy makers may select interventions for only political motives. This indicates the need for rational and transparent approaches to priority setting. Over the past decades, a number of approaches have been developed, including evidence-based medicine, burden of disease analyses, cost-effectiveness analyses, and equity analyses. However, these approaches concentrate on single criteria only, whereas in reality, policy makers need to make choices taking into account multiple criteria simultaneously. Moreover, they do not cover all criteria that are relevant to policy makers. Therefore, the development of a multi-criteria approach to priority setting is necessary, and this has indeed recently been identified as one of the most important issues in health system research. In other scientific disciplines, multi-criteria decision analysis is well developed, has gained widespread acceptance and is routinely used. This paper presents the main principles of multi-criteria decision analysis. There are only a very few applications to guide resource allocation decisions in health. We call for a shift away from present priority setting tools in health--that tend to focus on single criteria--towards transparent and systematic approaches that take into account all relevant criteria simultaneously.
    背景与目标: :卫生干预措施的优先级设置通常是临时的,资源没有得到最佳利用。潜在的问题是多个标准起着作用,并且决策很复杂。可以选择干预措施,以最大程度地提高总体人口健康,减少弱势或弱势群体的健康不平等,广告/或应对危及生命的情况,所有这些都涉及实际和预算方面的限制。这是决策者通常无助于理性解决的典型问题。他们倾向于使用启发式或直观的方法来简化复杂性,并且在此过程中,重要的信息将被忽略。接下来,政策制定者可能只出于政治动机选择干预措施。这表明需要采取合理和透明的方法来确定优先事项。在过去的几十年中,已经开发出许多方法,包括循证医学,疾病负担分析,成本效益分析和公平性分析。但是,这些方法仅集中于单个标准,而实际上,决策者需要在选择时同时考虑多个标准。此外,它们并未涵盖与决策者相关的所有标准。因此,有必要开发一种确定优先级的多标准方法,并且最近确实将其确定为卫生系统研究中最重要的问题之一。在其他科学学科中,多准则决策分析已经得到了很好的发展,已经得到了广泛的认可并被常规使用。本文介绍了多准则决策分析的主要原理。只有很少的应用程序可以指导健康状况中的资源分配决策。我们呼吁从目前卫生领域的优先重点设定工具(倾向于只关注单一标准)转变为同时考虑所有相关标准的透明,系统的方法。

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