NO对新生大鼠下丘脑钙激活钾通道的直接激活作用

目的：研究NO对下丘脑神经元钙激活钾通道（K_Ca）的作用及其机制。方法：采用膜片钳技术内面向外式。结果：NO可显著提高通道的开放概率，这种增强作用是通过延长通道开放时间及增加开放频率实现的。结论：下丘脑神经元中NO可直接激活K_Ca，它的病理生理作用还有待于进一步研究。     

大鼠下丘脑神经元L-型Ca~(2+)通道特性与Ba~(2+)浓度关系的研究

目的 :研究不同浓度Ba2 + 情况下 ,新生大鼠下丘脑神经元L -型Ca2 + 通道单通道特性。方法 :采用神经元的急性分离技术 ;用膜片钳细胞贴附式记录方式进行研究。结果 :110mmol/LBa2 + 为载流子与 10mmol/LBa2 + 为载流子时 ,单通道活动不同、电导不同 ,分别为 2 8 6pS和 19 1pS ,平均开放概率也明显不同。结论 :L -型Ca2 + 通道单通道电导、平均开放概率、激活与失活等电生理特性存在明显的Ba2 + 浓度依赖性。     

大鼠细动脉平滑肌细胞内酸中毒对ATP敏感钾通道的影响

目的：研究细胞内酸中毒对细动脉平滑肌细胞膜ＫＡＴＰ通道的影响。方法：应用膜片钳技术的内面向外式记录酶性分离的细动脉平滑肌上ＫＡＴＰ通道。结果；当细胞内无ＡＴＰ时，细胞内酸中毒降低通道电导，通道平均开放时间和开放时间长成分有所增大，对通道开放概率无明显影响；     

ATP敏感的K~+通道及其在缺氧预适应中的作用

ＫＡＴＰ通道是Ｎｏｍａ于１９８３年在心肌细胞上发现的［１］。随后在胰岛β细胞、骨骼肌细胞、血管与非血管平滑肌细胞以及神经细胞等多种细胞也都陆续发现ＫＡＴＰ通道的存在，并对其中的胰岛β细胞和下丘脑腹内侧核神经元的ＫＡＴＰ通道进行了较深入的研究［２，３］。ＫＡＴＰ通道的发现将细胞的生物能态与细胞的膜电位联结了起来，在许多细胞的代谢与电活动之间提供重要联系，为了解各种细胞反应的内在机理提供了新的渠道［１３］。ＫＡＴＰ通道是一种对Ｋ＋具有高度选择性的离子通道，对Ｎａ＋／Ｋ＋通透性比值仅为０．０１，在１…     

大鼠下丘脑神经元L-型Ca通道特性与Ba浓度关系的研究

目的:研究不同浓度Ba²⁺情况下,新生大鼠下丘脑神经元L-型Ca²⁺通道单通道特性。方法:采用神经元的急性分离技术;用膜片钳细胞贴附式记录方式进行研究。结果:110mmol/LBa²⁺为载流子与10mmol/LBa²⁺为载流子时,单通道活动不同、电导不同,分别为28.6pS和19.1pS,平均开放概率也明显不同。结论:L-型Ca²⁺通道单通道电导、平均开放概率、激活与失活等电生理特性存在明显的Ba²⁺浓度依赖性。     

心肌L型钙通道/电流及其在心肌肥大和心力衰竭时的变化

心肌细胞电活动的基础就是各种通道的离子流。有两类离子流左右心肌细胞的电活动 :一类是内向离子流 ,包括Ｉｎａ、Ｉｎａ-ｂ、Ｉｆ、Ｉｃａ-Ｌ、Ｉｃａ-Ｔ;另一类是外向离子流 ,包括Ｉｔｏ(Ｉｔｏ1 、Ｉｔｏ2 )、ＩＫ(ＩＫｒ、ＩＫｓ、Ｉｋｐ)、ＩＫ1 、ＩＫ -ＡＴＰ、ＩＫ -Ａｃｈ等。心肌细胞的钙通道 /电流属内向电流 ,可分为两大类 :(1 )Ｌ型Ｃａ2 通道 /电流(ＩＣａ-Ｌ) ,它在决定心肌细胞动作电位平台期的内向电流和启动心肌细胞兴奋 -收缩耦联都发挥极其重要的作用。 (2 )Ｔ型Ｃａ2 通道 /电流 (Ｉｃａ-Ｔ) ,它可能在心脏起搏细胞…     

人胚胎下丘脑—腺垂体系统P物质,生长抑素,亮啡肽和甲啡肽神经元的发…

用免疫组化方法观察了Ｐ物质（ＳＰ），生长抑素（ＳＲＩＦ），亮啡肽（Ｌ－ＥＮＫ），甲啡肽（Ｍ－ＥＮＫ）在１６－２４周胎儿下丘脑及腺垂体内的发育与分布。结果表明：在１６周胎儿下丘脑已出现ＳＰｅＳＲＩＦ－ＥＮＫ和Ｍ－ＥＮＫ阳性神经元，第三脑室室管膜上皮呈阳性染色。下天脑的变化以１６－２４周最为明显，，在１６周阳性细胞多为小神经元，分布疏散，２０－２４周阳性细胞为梭形和多极神经元，主要分布干室周核，室旁核     

自发性高血压大鼠弓状核β-内啡肽免疫反应阳性神经元的变化

目的：为探讨弓状核与高血压的关系提供形态学基础。材料和方法：用免疫组织化学ＰＡＰ法和像分析技术对７只雌性自发性高血压大鼠（ＳＨＲ）和７只雌性正常血压大鼠（ＷＫＹ）下丘脑弓状核β－内啡肽免疫反应阳笥神经元的形态、数目的灰度值进行了观察。结果ＳＨＲ鼠下丘脑弓核核β－内啡肽免疫反应阳怀神经元较密集,以着色深的强阳性细胞为主,ＷＫＹ鼠下丘脑弓状核β－内啡肽免疫反应阳性神经元则较稀疏,以着色浅的弱阳性细胞     

培养海马神经元突触外NMDA受体通道电流在发育中的变化

为观察培养大鼠海马神经元突触外NMDA受体通道电流在发育中的变化,本研究采用膜外面向外模式记录突触外NMDA受体介导的单通道电流。结果显示:培养2周神经元的电流幅度和开放概率比培养1周神经元大,但电导和翻转电位无显著差异。培养2周神经元只出现高电导开放,培养1周神经元同时出现高电导和低电导两种开放形式。NR2B受体亚型的特异性拮抗剂ifenprodil可降低培养1周和2周海马神经元的电流幅度、电导和开放概率,且对培养2周神经元开放概率的抑制作用更明显。以上结果表明,培养海马神经元突触外NMDA受体通道电流有发育变化,且培养1周神经元突触外NMDA受体的NR2亚型可能为NR2B和NR2D;而神经元培养到2同时,突触外主要为NR2B亚型,且数量有所增加。     

心肌钾通道的研究进展

心肌细胞膜上的钾通道亚型多，性质复杂。各个钾通道的电导值、门控动力学特征、离子动力学特征、通道激动剂、阻断剂均不同，在动作电位的形成中有着各自的作用。心脏几种重要的钾通道包括ＩＫ１、ＩＫ、Ｉｔｏ、ＩＫ（ＡＴＰ）。心脏疾病时ＩＫ１、Ｉｔｏ、ＩＫ（ＡＴＰ）的活性和功能发生改变。各个钾通道的全面认识有赖于膜片钳技术和分子生物学的深入研究。     

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.     

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.     

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.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'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.     

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.     

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.     

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.