Neuropilin-1与血管内皮生长因子在恶性肿瘤中的研究进展

随着有关Neuropilin(NRP)研究的进展,不仅揭示了NRP在神经系统发育过程中起着重要调节作用[1-2],最近还发现NRP是血管内皮生长因子(vascular endothelial growth factor,VEGF)的一种新型受体,许多研究表明,NRP在肿瘤生长、血管生成方面起着重要作用,并且可能作为许多肿瘤进展期的标志物之一[3].     

胶质细胞源性神经营养因子家族信号转导及其在神经系统中的作用

神经营养因子在神经元的存活、生长、分化、神经再生、突触形成与突触可塑性以及神经退行性疾病的过程中起着重要的作用,对它的研究已成为目前神经科学领域中的重要课题之一。胶质细胞源怀神经营养因子(glialcelllinederiredneurotrophicfactor,GDNF)家族配体包括GDNF,neurturin(NRTN),persephin(PSPN)和ARTNemin(ARTN),它们在结构和功能上有很大的相关性。GDNF家族受体由两类亚基组成,即GDNF受体Alpha亚基(GFRαs)和受体酪氨酸激酶RET亚基。GFRαs亚基又包括各亚型,即GFRα1～4。GDNF家族各营养因子与受体的相互作用、信号转到及其在神经系统中的作用是目前研究的热点。     

胶质细胞源性神经营养因子家族信号转导及其在神经系统中的作用

神经营养因子在神经元的存活、生长、分化、神经再生、突触形成与突触可塑性以及神经退行性疾病的过程中起着重要的作用，对它的研究已成为目前神经科学领域中的重要课题之一。胶质细胞源怀神经营养因子(glial cell hnederired neurotrophic factor，GDNF)家族配体包括GDNF，neurturin(NRTN)，persephin(PSPN)和ARTNemin(ARTN)，它们在结构和功能上有很大的相关性。GDNF家族受体由两类亚基组成，即GDNF受体Alpha亚基(GFRαs)和受体酪氨酸激酶RET亚基。GFRαs亚基又包括各亚型，即GFRα1～4。GDNF家族各营养因子与受体的相互作用、信号转到及其在神经系统中的作用是目前研究的热点。     

骨形态发生蛋白信号通路在牙本质发育中作用机制的研究进展

骨形态发生蛋白在牙本质发育过程中起着重要作用。骨形态发生蛋白在牙本质发育的各个阶段有着不同的表达,发挥其特定的作用。骨形态发生蛋白与其受体相互作用形成复合体,并将信号传导到典型的SMAD信号通路(如骨形态发生蛋白配体、受体和SMADS)和非典型的SMAD信号通路(如MAPKS、P38、ERK、JNK和PI3K/AKT),从而在牙本质发育和动态平衡过程中调节牙间充质干细胞的增殖和分化。本文就骨形态发生蛋白信号在成牙本质细胞分化和牙本质形成中的研究进展作一综述。     

Notch信号通路在儿童肿瘤中的作用

哺乳动物Notch蛋白包括四种(Notch1～Notch4),其配体分为Jagged和Delta两个家族.Notch通路由受体、配体及许多下游靶基因组成复杂的网络结构,调控着组织细胞的发育和生理过程,且在不同组织及细胞类型中起着致癌或抑癌作用.本文主要介绍Notch信号通路的调控及其在儿童肿瘤中的作用.     

白血病患者骨髓基质细胞中KDR和Sema3基因的表达特点

KDR与其配体血管内皮细胞生长因子(VEGF) 1 6 5介导肿瘤血管形成,参与实体瘤的生长、转移和播散[1 ] 。Sema3与其受体Neuropilin 1 (NP 1 )结合,除可以引导神经轴突生长,在骨髓细胞和血细胞中也有丰富的表达,并可调节血管发生。在内皮细胞中,KDR和Sema3的作用密切相关[2 ] 。推测二者在造血微环境调控中可能发挥一定作用。我们采用PCR ELISA检测两者在白血病和非血液病患者骨髓基质细胞(BMSC)中的表达,为探讨其在白血病异常造血调控中的作用提供理论依据。病例和方法1　研究对象及骨髓单个核细胞(BMMNC)的分离　细胞形态学和组…     

IL-33/ST2信号通路在心血管疾病中的研究进展

可溶性ST2蛋白(s ST2)是IL-1受体家族的成员,IL-33是ST2的特异性配体,IL-33/ST2信号通路在炎症反应和免疫疾病中发挥着重要作用;已经证实ST2是一种心肌蛋白,在张力负荷增加的心肌细胞中表达增多,可阻断IL-33抗心肌细胞肥大和心肌纤维化的作用,导致心肌重构。研究发现ST2参与了动脉硬化过程,使高血压的发生风险增加;高浓度的s ST2与冠心病和心力衰竭的活动性和预后相关;醛固酮受体拮抗剂在IL-33/ST2信号通路的起着重要作用。     

Toll样受体与疾病

天然免疫反应是机体抵御外界微生物感染的第一道防线。固有免疫系统通过模式识别受体(PRRs)识别病原微生物的病原相关分子模式(PAMPs)。PAMPs在结构上相对保守,主要存在于微生物。Toll样受体家族是最重要的PRRs,通过识别相应的PAMPs介导天然免疫反应,同时通过DCs启动适应性免疫应答。另外,TLRs能够识别某些内源性的TLR配体,这些配体称之为损伤相关分子模式(DAMPs)。研究发现TLRs在抗感染、变态反应、自身免疫性疾病、肿瘤等疾病的发生发展过程中起着重要的作用。在深入研究Toll样受体及其信号通路的基础上,以其作为药物干预靶点,对治疗相关感染性疾病、自身免疫性疾病、变态反应性疾病等具有重要的科学意义和应用价值。     

环磷酸腺苷反应原件相关蛋白对抑郁症脑部区域特异性的研究进展

环磷酸腺苷(cAMP)反应原件相关蛋白(CREB)是转录因子蛋白家族成员,在所有脑细胞内表达。CREB定位在细胞核,能够将发生在细胞膜上的刺激信号转换成细胞核内基因表达的改变,在刺激－转录偶联中发挥重要作用。CREB通过调控基因表达来调节各种神经蛋白的表达,最终影响单个神经元或整个神经循环的功能,是多种抗抑郁药物发挥治疗作用的靶点。研究表明大脑不同区域内的CREB对抑郁症的影响不同。笔者综述CREB调节基因转录的分子机制,重点阐述CREB在抑郁症发生、发展过程中作用的多样性,从而探讨CREB对该疾病潜在的治疗价值。     

多个核受体调节ApoM表达的研究进展

核受体是一类可扩散并可与特异性配体结合的细胞内信号蛋白,存在于细胞质或细胞核内,它通过与配体结合后在细胞核内调节基因表达而使配体发挥作用。目前,主要将其分为3类[1]:第1类为甾体激素受体家族,如糖皮质激素受体(GR)α、β,盐皮质激素受(MR)及雌激素受体(ER)α、β;第2类为非     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.