Advanced cardiac morphogenesis does not require heart tube fusion

The bilateral cardiac mesoderm migrates from the lateral region of the embryo to the ventral midline, where it fuses to form the primitive heart tube. It is generally accepted that migration and fusion are essential for subsequent stages of cardiac morphogenesis. We present evidence that, in Foxp4 mutant embryonic mice, each bilateral heart-forming region is capable of developing into a highly differentiated four-chambered mammalian heart in the absence of midline fusion. These data demonstrate that left-right chamber specification, cardiac looping, septation, cardiac myocyte differentiation, and endocardial cushion formation are preprogrammed in the precardiac mesoderm and do not require midline positional identity or heart tube fusion.     

The mevalonate pathway controls heart formation in Drosophila by isoprenylation of Ggamma1

The early morphogenetic mechanisms involved in heart formation are evolutionarily conserved. A screen for genes that control Drosophila heart development revealed a cardiac defect in which pericardial and cardial cells dissociate, which causes loss of cardiac function and embryonic lethality. This phenotype resulted from mutations in the genes encoding HMG-CoA reductase, downstream enzymes in the mevalonate pathway, and G protein Ggamma1, which is geranylgeranylated, thus representing an end point of isoprenoid biosynthesis. Our findings reveal a cardial cell-autonomous requirement of Ggamma1 geranylgeranylation for heart formation and suggest the involvement of the mevalonate pathway in congenital heart disease.     

A single troponin T gene regulated by different programs in cardiac and skeletal muscle development

A cloned complementary DNA derived from a messenger RNA transiently present at low abundance levels in early chick embryonic skeletal muscle hybridizes to a messenger RNA present at high abundance levels in cardiac muscle. Genomic DNA hybridization and nucleotide sequence identity of complementary DNA's from both heart and skeletal muscle demonstrate that the messenger RNA's from both sources are encoded by the same gene. The encoded polypeptide is a troponin T sequence which is probably a cardiac isoform. This single copy troponin T isogene is governed by different regulatory programs in heart and skeletal muscle differentiation.     

山羊胚胎心脏发生发育的形态学研究

应用光镜观察了山羊胚胎心脏的发生和发育过程 ,结果表明 :15日龄 2 0时的胚胎处于胚层分化阶段 ,中胚层上已有微血管发生 ;16～ 18日龄的胚胎在前肠门两侧发生两条对称的心内皮管 ;18～ 2 0日龄的胚胎在前肠腹面两条心内皮管合并成单管状心。同时 ,心管发生扭曲 ,心管内部开始分隔过程 ;2 0～ 34日龄的胚胎心脏的分隔基本完成 ;34～ 10 5日龄属于胚胎心脏进一步发育成熟的阶段。试验还发现山羊心骨骼中的纤维三角发生初期是由致密结缔组织构成 ,随着胚胎的发育转变为透明软骨 ,具有种特异性     

优秀散打运动员心脏泵血功能 对模拟比赛情景的应答变化特征

采用模拟比赛情景训练的方法，对16名高水平散打运动员运动过程中的心脏泵血功能变化进行研究，探究其应答及变化规律。结果表明：（1）心泵功能：HR和LVET呈相反方向变化；SV、CO、SI、CI变化呈峰形，第二回合达最高，回合间指标存在差异，P<0.05；（2）心肌收缩力：dz/dtmax、HI呈峰形，第二回合达最高；Q-Z间期逐步减小；回合间指标存在差异，P<0.05；（3）心脏做功：CWI呈逐步上升趋势，回合间呈显著差异，P<0.05；（4）心血管机能：SP 、MAP逐步上升；DP、TPR前两回合逐步下降，第三回合上升；C逐步下降。第一、二回合比，SP、DP、TPR存在差异，P<0.05；二、三回合比，MAP、C存在差异，P<0.05。结论：部分心脏泵血功能指标对模拟比赛具有较高的应答性，且呈现特定的规律，这对选拔散打人才，评估散打运动员心脏功能，科学指导散打训练提供了参考。     

蒙古绵羊早期胚胎心脏的组织发生

蒙古绵羊早期胚胎的血岛是心管及血管组织发生的原基。交配后１２～１３日龄,在胚盘两侧的胚内中胚层内,首先发生血岛,进而扩展到原肠及尿囊的脏层。在１６～１８日龄,前肠腹面的心管,由单管状变形成Ｕ字袢,进而扭转成字形。因心管中段的收缩,出现心房、心室及动脉球三个膨大。２０～３０日龄,胚长４～１５ｍｍ,在房室管内,发生前后对称的心内膜垫,将房室管分隔成左及右房室口。由于心房内,第Ⅰ第Ⅱ房间隔发生,将心房分隔成左及右心房。再由于心室内室间隔的发生,将心室分隔成左及右心室。心管传导系统的窦房结,在１６～１８日龄,发生于静脉窦右侧心外膜下,此时心管的窦房部开始搏动。本文发现,在２１～２２日龄,胚长６～８ｍｍ时,静脉窦右侧心外膜下的窦房结细胞团散在。在房间隔壁内与心内膜垫相接处,房室结的细胞团群居。还发现,绵羊胚胎的心软骨原基,发生于３０日龄,胚长１５ｍｍ时,心软骨原基位于主动脉半月瓣外围水平上与肺动脉之间。     

斑马鱼hoxb4a在心脏发育中的功能

斑马鱼转录因子hoxb4a在心脏中的功能未见研究报道,为了阐明hoxb4a在心脏发育中的作用,本文利用基因沉默技术和mRNA基因过表达方法,分别在斑马鱼中敲降和过表达hoxb4a基因,发现抑制或过表达hoxb4a的胚胎在第3天出现心包腔肿大、心脏环化异常的表型。通过原位杂交技术对野生型及hoxb4a敲降胚胎进行心肌特异基因的原位杂交染色比较,测量结果显示hoxb4a敲降胚胎的心脏环化角度增大（P<0.01）。接着利用转基因鱼系,发现敲降hoxb4a后的胚胎存在鳃弓异常、心内膜畸形的表型。进一步使用qPCR检测hoxb4a沉默后心脏相关基因的表达量变化, 结果显示 hoxb4a敲降后,多数心脏发育关键基因出现显著性下调,而调控心脏腔室分化的关键基因nppa明显上调（P<0.05）。本研究表明斑马鱼hoxb4a沉默会导致心脏结构畸形、环化异常,并且调控了早期心脏发育基因的变化。本研究发现了hoxb4a在斑马鱼早期心脏发育中发挥作用,并通过原位杂交及qPCR结果初步探索了hoxb4a调控心脏腔室的分化及心脏环化过程,深化了人们对心脏发育调控网络的认识。     

斑马鱼早期胚胎神经形成过程中SOD表达特点研究

为了解以超氧化物歧化酶（Superoxide dismutase,SOD）为代表的抗氧化酶系统在胚胎发育过程中的建立及其对胚胎发育的影响,通过免疫组化方法,研究了SOD在斑马鱼早期胚胎发育神经系统中的表达特点。结果表明,在体节分化的不同时期,SOD在脊索、神经管、眼等部位呈不同程度的表达;咽弓形成时期,SOD在咽弓中表达微弱,在脑组织中表达较强;至孵化期,SOD在终末器官中的表达程度不尽相同,其在大脑区域的表达略强于间脑区域。说明在斑马鱼早期胚胎神经形成过程中,以SOD为代表的抗氧化酶系统已经开始逐步形成,维持胚胎组织细胞中活性氧（ROS）的正常浓度,确保胚胎正常发育。     

Echo-planar imaging: magnetic resonance imaging in a fraction of a second

Progress has recently been made in implementing magnetic resonance imaging (MRI) techniques that can be used to obtain images in a fraction of a second rather than in minutes. Echo-planar imaging (EPI) uses only one nuclear spin excitation per image and lends itself to a variety of critical medical and scientific applications. Among these are evaluation of cardiac function in real time, mapping of water diffusion and temperature in tissue, mapping of organ blood pool and perfusion, functional imaging of the central nervous system, depiction of blood and cerebrospinal fluid flow dynamics, and movie imaging of the mobile fetus in utero. Through shortened patient examination times, higher patient throughput, and lower cost per MRI examination, EPI may become a powerful tool for early diagnosis of some common and potentially treatable diseases such as ischemic heart disease, stroke, and cancer.     

Molecular basis for the influence of muscle length on myocardial performance

According to Starling's law of the heart, the force of contraction during the ejection of blood is a function of the end-diastolic volume. To seek the molecular explanation of this effect, a study was made of the effects of length on Ca2+ sensitivity during tension development by isolated demembranated cardiac muscle in which the cardiac form of troponin C was substituted with skeletal troponin C. The results of troponin C exchange were compared at sarcomere lengths of 1.9 and 2.4 micrometers. Enhancement of the myocardial performance at the stretched length was greatly suppressed with the skeletal troponin C compared with the cardiac troponin C. Thus the troponin C subunit of the troponin complex that regulates the activation of actin filaments has intrinsic molecular properties that influence the length-induced autoregulation of myocardial performance and may be a basis for Starling's law of the heart.     

Transient regenerative potential of the neonatal mouse heart

Certain fish and amphibians retain a robust capacity for cardiac regeneration throughout life, but the same is not true of the adult mammalian heart. Whether the capacity for cardiac regeneration is absent in mammals or whether it exists and is switched off early after birth has been unclear. We found that the hearts of 1-day-old neonatal mice can regenerate after partial surgical resection, but this capacity is lost by 7 days of age. This regenerative response in 1-day-old mice was characterized by cardiomyocyte proliferation with minimal hypertrophy or fibrosis, thereby distinguishing it from repair processes. Genetic fate mapping indicated that the majority of cardiomyocytes within the regenerated tissue originated from preexisting cardiomyocytes. Echocardiography performed 2 months after surgery revealed that the regenerated ventricular apex had normal systolic function. Thus, for a brief period after birth, the mammalian heart appears to have the capacity to regenerate.     

Prion-induced amyloid heart disease with high blood infectivity in transgenic mice

We investigated extraneural manifestations in scrapie-infected transgenic mice expressing prion protein lacking the glycophosphatydylinositol membrane anchor. In the brain, blood, and heart, both abnormal protease-resistant prion protein (PrPres) and prion infectivity were readily detected by immunoblot and by inoculation into nontransgenic recipients. The titer of infectious scrapie in blood plasma exceeded 10(7) 50% infectious doses per milliliter. The hearts of these transgenic mice contained PrPres-positive amyloid deposits that led to myocardial stiffness and cardiac disease.     

Molecular mechanics of cardiac myosin-binding protein C in native thick filaments

The heart's pumping capacity results from highly regulated interactions of actomyosin molecular motors. Mutations in the gene for a potential regulator of these motors, cardiac myosin-binding protein C (cMyBP-C), cause hypertrophic cardiomyopathy. However, cMyBP-C's ability to modulate cardiac contractility is not well understood. Using single-particle fluorescence imaging techniques, transgenic protein expression, proteomics, and modeling, we found that cMyBP-C slowed actomyosin motion generation in native cardiac thick filaments. This mechanical effect was localized to where cMyBP-C resides within the thick filament (i.e., the C-zones) and was modulated by phosphorylation and site-specific proteolytic degradation. These results provide molecular insight into why cMyBP-C should be considered a member of a tripartite complex with actin and myosin that allows fine tuning of cardiac muscle contraction.     

Control of stress-dependent cardiac growth and gene expression by a microRNA

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of alpha-myosin heavy chain (alphaMHC) and up-regulation of betaMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism. Thus, the alphaMHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.     

东方蝾螈、太行隆肛蛙、丽纹龙蜥心脏的比较组织学研究

采用H．E．染色、显微镜观察法对东方蝾螈、太行隆肛蛙、丽纹龙蜥的心脏进行研究．结果显示：东方蝾螈、太行隆肛蛙心脏结构基本相同,丽纹龙蜥的心脏与二者有一定差别．3种动物的心脏均为两心房一心室,但丽纹龙蜥的心室开始出现不完全分隔,为不完全的双循环系统;红细胞均为有核红细胞;心脏壁有内、中、外3层结构,分别为心内膜、心肌层及心外膜．心内膜位于心脏内层,表面是一层不规则的多角形内皮细胞,胞核为椭圆形．心肌层主要由心肌纤维构成,心肌纤维间充满结缔组织和血管．心肌纤维由心肌细胞组成,胞核呈圆形或椭圆形,位于细胞中央．心外膜位于外层,由结缔组织构成,内含较多弹性纤维．3种动物心脏结构的差别是两栖类、爬行类动物在进化过程中对环境不断适应的结果．     

反义抑制miR-202引起斑马鱼早期胚胎发育异常研究

为了探讨miR-202在鱼类胚胎发育中的功能,采用实时定量反转录PCR技术和整体原位杂交技术检测了miR-202在斑马鱼胚胎发育阶段的表达。结果发现miR-202是母源性分子并在斑马鱼胚胎发育过程中持续表达,尤其在早期胚胎发育阶段表达水平较高。在此基础上,采用基因沉默技术在斑马鱼受精卵中显微注射miR-202的反义锁核苷酸,实时荧光定量反转录PCR技术和整体原位杂交技术结果显示miR-202反义锁核苷酸可以显著下调斑马鱼胚胎中miR-202表达水平,同时发现反义抑制miR-202后胚胎发育停滞在4 hpf时左右。共同注射miR-202前体可以部分挽救反义抑制miR-202后导致的胚胎发育停滞。本研究证明miR-202在斑马鱼胚胎发育过程中起着重要的调控作用,其功能是斑马鱼胚胎早期发育所必需的。为进一步探索miR-202在鱼类胚胎发育过程的功能奠定了基础。     

Chimeric and ex-parabiotic frogs (Rana pipiens): specificity of tolerance

Rejection of orthotopic neural-fold transplants may be prevented by either embryonic parabiosis or reciprocal exchange of presumptive blood. These observations form the basis of the no blood-no tolerance hypothesis, which states that persistent tolerance by the host requires that the somatic transplant be accompanied by presumptive blood from the donor. Regarding parabionts and chimeras as special cases of transplantation of whole or partial animals, I found that ex-parabionts accept subsequent skin exchanges only from the homologous ex-parabiont; reciprocal chimeras are compatible provided each animal portion contains a primary blood source, and will accept transplants as frogs only from the homologous recombinant. Chimeric recombinations made anterior to the heart field prove incompatible and fail to survive to maturity. Successful chimeras as well as ex-parabionts survive to maturity and are apparently normal in every antigen, radiation, and drugs.     

不同马铃薯品种脱毒试管苗对早疫病的抗性鉴定

为有效而快速评价不同马铃薯品种对马铃薯早疫病的抗性水平,选取D5、D19、D30、A1、B1、C3的6个马铃薯品种的脱毒试管苗和马铃薯早疫病菌为试验材料,将脱毒试管苗接种马铃薯早疫病菌,调查其生长情况。结果表明,脱毒试管苗接种适当浓度的早疫病孢子囊悬浊液,可判断不同品种的马铃薯试管苗的抗性,其中,B1品种抗病性表现最强。使用孢子悬浊液接种马铃薯脱毒试管苗是可行的,可用于对抗性资源的早期评价。     

活动平板试验配合心脏放射性核素检查诊断冠心病的价值（附53例报告）

对临床拟诊为冠心病５３例作活动平板试验并配合心核素检查的结果显示：双阳性２６例（４９．１％），平板试验阳性／心核素检查阴性４例（７．５％）；平板试验阴性／心核素检查阳性１４例（２６．４％）；双阴性９例（１７％）。表明双阳性可肯定冠心病的诊断，双阴性可否定诊断。平板试验阴性／心核素检查阳性，应结合临床做出诊断，平板试验阳性／心核素检查阴性为冠心病的危险因素，宜长期随诊。     

袁肇凯教授辨证治疗心病经验

本文主要从病因病机、辨证论治规律及遣方用药特色等几个方面介绍袁肇凯教授治疗心病（冠心病、心律失常、慢性心力衰竭）的经验,疗效显著。袁教授认为冠心病的主要病机为本虚标实,本虚责之于心气阴两虚、阳气不足为主,标实责之于寒凝、气滞、痰阻、血瘀,且诸邪每多夹杂,主张补通二法作为本病防治的重要原则。心律失常辨证的关键在于分清寒热属性,快速性心律失常辨证多为心气阴两虚证治以益气养阳,镇静安神;缓慢性心律失常辨证多为心阳气亏虚证,或心脾两虚证治以温阳养心,复脉安神;慢性心力衰竭的主要病机为心肾阳气虚衰,血瘀水停,临证以强心扶阳、温肾利水为法治疗。