心肌肥大的信号转导机制

编者按：细胞信号转导在当今生命科学领域占有极其重要的地位,自20世纪90年代以来,与细胞信号转导有关的研究已两度获诺贝尔医学奖,由此可见一斑。以此为契机,探索疾病的信号转导机制已成为当前国际上倍受瞩目的热点课题。心肌肥大和心力衰竭是大多数心血管疾病的严重或终末阶段,研究其细胞信号转导机制改变及其在发病学中的作用具有非常重要的意义。本专题重点介绍目前这一领域的研究进展,内容涉及心肌肥大和心力衰竭时细胞内信号转导通路的改变、心力衰竭时肾上腺素受体及其信号转导机制的改变等方面。尤其值得一提的是,本专题还包…     

肥大心肌钠钙交换体的调控机制

心肌肥大是心脏对几乎所有引起心脏病变因素的一种适应性反应,虽然心肌肥大是心脏维持正常心输出量的一种有效代偿机制,但是持续的心肌肥大会导致失代偿而发生扩张性心肌病、心衰和猝死.是心血管病患者死亡的重要原因之一.     

心室重构中的心肌细胞凋亡

心力衰竭的最重要特征是心肌结构和功能改变而引起的心室重构,这不仅与细胞肥大、蛋白合成及细胞外基质增多有关,而且还涉及到心肌细胞凋亡,并且认为心肌细胞凋亡可能是心肌功能进行性恶化的重要机制之一。     

硫化氢在心力衰竭干预中的作用

目前临床上对心力衰竭的防治还没有较好的策略。H2S是一种具有多种生理学功能的内源性气体信号分子,且具有心肌保护功能。H2S对动脉粥样硬化、心肌肥大、氧化应激和同型半胱氨酸的影响,以及它在心力衰竭中的作用越来越受到人们的关注。     

心肌收缩蛋白的结构与功能研究进展

心肌收缩蛋白是心肌产生收缩的物质基础。本文介绍了两种主要心肌收缩蛋白：肌凝蛋白和肌动蛋白的结构，尤为详细地讨论了与其功能相关的部分，就正常与异常心脏中两者的改变作一阐述，以期深化心肌肥大和心力衰竭分子水平上的变化认识。     

达利全对心力衰竭大鼠β_1、β_2、β_3肾上腺素能受体的影响

目的研究达利全(α_1肾上腺素受体阻断剂、β肾上腺素受体非选择性阻断剂)对升主动脉缩窄压力超负荷心力衰竭大鼠β_1、β_2、α_3肾上腺素能受体(β_1AR、β_2Ar、β_3AR)表达的影响,探讨达利全改善心力衰竭的新机制。方法将升主动脉缩窄术后心力衰竭Wistar雌性大鼠随机分为4组,一组为心力衰竭组,给予生理盐水灌胃,每日2次(n=10);其余3组为治疗组,治疗组分别给予达利全3mg/Kg、达利全12.5mg/Kg、达利全50mg/Kg,灌胃,每日2次(n=10);治疗12周。同时制备模型设置假手术组作为对照(n=10),不予处置。观察各组大鼠各项指标变化。结果与假手术组对比,心力衰竭鼠心肌细胞β_1ARmRNA表达显著降低(P<0.05),而β_3ARmRNA表达显著升高(P<0.05),药物治疗12周后,与心力衰竭组对比,β_1ARmRNA表达显著升高,β_3ARmRNA表达显著降低,且随剂量增加作用越明显(P<0.05);β_2AR mRNA表达各组之间无明显差异(P>0.05)。结论达利全通过调节心肌细胞内β_1ARmRNA和β_3ARmRNA表达,缓解心力衰竭症状。     

免疫细胞在心肌重塑中的作用

心肌重塑几乎与所有类型的心脏疾病的发生发展相关,是一个重要的全球性健康问题.这种病理性重塑过程包括心室扩张、心肌炎症反应和心肌细胞肥大,最终导致心力衰竭的发生.在各种类型的心肌损伤后,心脏从纤维细胞转化为肌成纤维细胞,随后并沉积在细胞外基质中,这是心肌纤维化的重要病理机制.同时免疫细胞的激活及其介导的炎症反应也参与了心肌重塑的发生与发展,因而了解免疫细胞导致心肌重塑的可能病理机制可为临床防治和逆转心肌重塑提供新的靶点.     

雄性大鼠心肌雄激素受体及其mRNA的表达

目的观察雄激素受体(AR)蛋白及其mRNA在大鼠心肌的表达。方法采用免疫组织化学方法和原位杂交的方法观察成年(3月龄)Wistar大鼠心肌中AR阳性神经元的存在及其表达。结果大鼠心肌中存在AR阳性神经元和ARmRNA阳性神经元。结论为AR在心脏的存在提供形态学依据,并在基因水平证实部分心肌细胞中存在雄激素受体的结合位点,提示心肌细胞可能受雄激素影响。     

泛素-蛋白酶体系统在心肌梗死中的病理生理意义

心肌梗死后心室重塑是慢性心力衰竭的主要原因.因凋亡和坏死而导致的心肌细胞死亡可造成心肌重塑,病理性心肌肥大和左心室扩张是其主要特征.研究表明,泛素蛋白酶体系统(ubiquitin proteasome system,UPS)可能参与这一过程.     

心肌肥大肽研究进展

心肌肥大肽是一种新发现的心脏分泌的活性肽，为目前最强的致心肌肥大物质。现已克隆出心肌肥大肽的基因。心肌肥大肽通过促进心肌细胞生长及细胞间质增生而起作用     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.