氯化锂对成年小鼠海马神经发生的影响

目的：观察氯化锂(LiCl)对成年小鼠海马细胞增殖与神经发生的影响。方法：用5-溴-2-脱氧尿核苷(BrdU)标记新生细胞，免疫组化染色后统计新生细胞数量；应用BrdU与抗微管蛋白单克隆抗体(JuJI)／抗胶质纤维酸性蛋白多克隆抗体(GFAP)双标记，鉴别出BrdU阳性细胞的细胞类型。结果：LiCl组小鼠海马齿状回细胞增殖与神经发生明显强于对照组；新增殖的细胞约有70％为神经元，5％左右为神经胶质细胞。结论：LiCl增强了成年小鼠海马齿状回的细胞增殖与神经发生，这一功能对于中枢神经系统退行性疾病的预防与治疗可能有重要的意义。     

营养不良可增加幼鼠齿状回颗粒下层的细胞增殖和神经生发(英文)

为了观察营养不良对幼鼠海马齿状回 (DG)和脑室下层 (SVZ)的细胞增殖和神经发生的影响 ,采用 5 -溴 -2 -脱氧尿苷(Brd U)标记结合免疫组织化学方法对脑切片分别进行 Brd U、Tu J1(β tubulin,β微管蛋白 )及 GFAP(胶质纤维酸性蛋白 )反应或双重反应。结果表明 ,营养不良幼鼠齿状回的细胞增殖和神经生发明显高于营养良好的幼鼠而脑室下层的细胞增殖数量在两者却无明显差异。在齿状回 ,新生的细胞中大约有 5 0 %为新生的神经元 ,10～ 2 0 %为神经胶质细胞。本文结果提示 ,幼鼠海马齿状回的细胞增殖和神经生发可能因营养不良而增加 ,这些新生的细胞可能对日后某些海马依赖性行为产生一定的影响     

氯化锂促进不同年龄成年小鼠齿状回细胞增殖与神经发生

目的观察氯化锂(LiCI)对不同年龄成年小鼠齿状回细胞增殖与神经发生的影响。方法以氯化锂喂养动物，用5-溴-2’-脱氧尿核苷(BrdU)标记新生细胞，免疫组织化学染色后统计新生细胞数量；应用BrdU与TuJl／GFAP双标记，鉴别出BrdU阳性细胞的细胞类型。结果不同年龄成年小鼠齿状回的BrdU阳性细胞形态无明显差别，48周龄组阳性细胞的数量明显低于8周龄组；LiCI组小鼠新增殖细胞明显多于对照组，其中约有70％为神经元，4％～5％左右为神经胶质细胞。结论服用LiCI可显著增强成年小鼠齿状回的细胞增殖与神经发生，部分逆转其随年龄增长而逐渐减低的趋势，对于中枢神经系统退行性疾病的预防与治疗可能有重要的意义。     

BMP4参与海人酸损伤后成年大鼠海马齿状回颗粒细胞增殖及胶质增生

目的探讨海人酸（KA）侧脑室注射致大鼠海马损伤后骨形成蛋白-4（BMP4）的表达变化及其与颗粒细胞增殖和胶质细胞增生的关系。方法将成年大鼠分为对照组与实验组。侧脑室注射KA7d后,用尼氏染色检测海马神经元丢失,用免疫组织化学与原位杂交的方法检测海马齿状回BMP4mRNA阳性细胞与BrdU标记细胞、GFAP阳性细胞数的变化。结果正常成年大鼠BMP4mRNA阳性细胞主要分布于海马齿状回的门区、颗粒下层、CA3、CAI区。BrdU标记细胞主要分布在齿状回颗粒下层。GFAP阳性细胞主要分布在齿状回、CA3区。在KA侧脑室注射致海马损伤后7d,海马CA3、CA4区神经元丢失明显,BMP4mRNA阳性细胞与BrdU、GFAP阳性细胞均明显增加。结论KA侧脑室注射致海马损伤后,成年大鼠海马齿状回颗粒细胞增殖增强和胶质增生可能与BMP4表达增加有关。     

成年大鼠脑损伤后海马新生神经元功能特点的研究

目的：观察弥漫性脑损伤后海马齿状回新生神经元GAD67和Fos蛋白的表达，探讨海马齿状回新生神经元的功能特点。方法：参考Marmarou方法制作大鼠弥漫性脑损伤模型，采用BrdU标记和免疫荧光组织化学方法并结合激光共聚焦显微镜技术观察海马齿状回中BrdU阳性细胞GAD67的表达和二次致伤后Fos蛋白的表达情况。结果：①成年大鼠弥漫性脑损伤后海马齿状回颗粒细胞层中的BrdU免疫阳性细胞可表达GAD67，而位于亚颗粒增生带的BrdU免疫阳性细胞未见GAD67表达；②在病理刺激下，成年大鼠弥漫性脑损伤后齿状回颗粒细胞层内的BrdU免疫阳性细胞可表达Fos蛋白。结论：弥漫性脑损伤后齿状回颗粒细胞层中的新生神经元不仅可以表达神经活性递质而且能够被病理刺激激活，具有与成熟神经元相似的功能特点。     

高原环境对小鼠成体神经发生的影响

目的:探索和研究我国青藏高原高海拔生存环境对于小鼠海马齿状回成体神经干细胞增殖和新生细胞分化的影响。方法:健康成年昆明小鼠分为两组,一组为1519 m海拔高度的兰州对照组,另一组为4547 m海拔高度的青藏高原沱沱河高原环境组。运用BrdU腹腔注射和免疫荧光组织化学相结合的方法研究和比较不同环境中齿状回内成体神经干细胞的增殖和新生细胞的分化。结果:高原环境组的BrdU免疫阳性细胞数与低海拔对照组相比减少了40%(P=0.001),而高原环境组小鼠齿状回中的BrdU/Prox-1标记的双阳性细胞在BrdU标记的阳性细胞中的百分比与对照组相比没有显著的差异(P=0.211),并且两组小鼠齿状回中90%以上的BrdU阳性细胞同时也被Prox-1标记。结论:在青藏高原的高海拔低氧环境中,小鼠海马内成体神经干细胞的增殖明显受抑制,然而新生的细胞向颗粒细胞的分化并没有受到明显的影响。     

模拟失重后大鼠海马齿状回神经发生的实验研究

观察模拟失重对大鼠海马齿状回神经发生的影响,为进一步阐明模拟失重对成年大鼠海马齿状回神经发生影响的规律及其相关生物学机制提供基本的实验依据。采用尾部悬吊法建立大鼠模拟失重模型,通过5-溴-2’-脱氧尿苷(5-bromo-2’-de-oxyuridine,BrdU)标记分裂细胞、微管相关蛋白(doublecortin,DCX)标记神经干细胞、神经元核蛋白(NeuN)标记神经元及胶质原纤维酸性蛋白(GFAP)标记神经胶质细胞的单、双重免疫组织化学染色方法比较尾部悬吊后7、14、28d模拟失重组大鼠与相应时间对照组大鼠之间海马齿状回神经前体细胞增殖、迁移和分化的情况。结果显示:模拟失重后7、14d尾部悬吊法模拟失重大鼠齿状回的BrdU免疫阳性细胞数目较相应对照组明显减少(P<0.01),而模拟失重后28d时两组大鼠齿状回BrdU免疫阳性细胞数目无显著差异(P>0.05)。本研究结果提示,模拟失重可抑制海马齿状回神经发生的水平。     

BrdU标记法检测不同年龄阶段小鼠神经前体细胞的增殖潜能****

背景：BrdU是胸腺嘧啶核苷类似物,常用来标记前脑室管膜下区具有增殖潜能的神经前体细胞。 目的：建立不同年龄阶段BrdU标记方法,系统分析不同年龄阶段神经前体细胞增殖特点以及变化规律。 方法：选取胚胎期小鼠、新生小鼠、成年小鼠和老年小鼠各5只,腹腔注射BrdU,观察不同年龄阶段神经前体细胞增殖潜能及不同年龄阶段前脑衰老细胞,探讨微环境对神经前体细胞增殖潜能的影响。 结果与结论：胚胎期小鼠、新生小鼠、成年小鼠和老年小鼠前脑室管膜下区BrdU+细胞分别为(897.20±22.38),(262.17±26.26),(76.67±5.63),(43.8±2.61)个,随年龄增加细胞增殖潜能逐渐降低(P < 0.05)。成年小鼠和老年小鼠脑室周围有大量β-半乳糖苷酶染色阳性衰老细胞,说明随年龄增加脑内β-半乳糖苷酶染色活性增强,衰老细胞逐渐增多,神经前体细胞生存微环境失衡可能与神经前体细胞增殖潜能下降有关。     

Proliferation and differentiation of neural precursors in hippocampus and dentate gyrus after intracerebral hemorrhage in adult rats

目的:观察成年大鼠脑出血后海马齿状回神经前体细胞的增殖与分化,探讨脑出血后神经前体细胞的变化规律.方法:制作大鼠脑出血模型,5-溴脱氧尿嘧啶核苷(BrdU)腹腔注射标记增殖细胞,用免疫组织化学法检测大鼠海马齿状回BrdU、神经元核抗原(NeuN)、胶质纤维酸性蛋白(GFAP)阳性细胞数的变化.结果:正常组和假手术组大鼠海马齿状回均有少量BrdU阳性细胞,脑出血后大鼠各时间段的BrdU阳性细胞均较正常组和假手术组增加,7d组达到峰值后逐渐下降,28 d组仍高于正常组和假手术组.正常成年大鼠海马齿状回可见少量BrdU/NeuN和BrdU/GFAP双标阳性细胞,脑出血后双标阳性细胞数较正常组增加.结论:脑出血后大鼠海马齿状回神经前体细胞增殖明显,且可以向神经元和神经胶质细胞分化.     

成年和老年大鼠局灶性脑缺血后脑室下区细胞的增殖分化

目的：比较老年和成年大鼠局灶性脑缺血后脑室下区（SVZ）神经干细胞的增殖与分化。方法：制作大脑中动脉梗死模型,用免疫组化法检测SVZ的5-溴脱氧尿核苷（BrdU）、神经元核抗原（NeuN）及胶质纤维酸性蛋白（GFAP）阳性细胞数的变化。结果：SVZ的BrdU阳性细胞在正常组和假手术组成年大鼠明显多于老年大鼠。实验组成年和老年大鼠均在缺血后增加,28d时仍高于正常水平,但成年大鼠各时间点均明显高于老年大鼠。在新生细胞中部分细胞是Brdu／NeuN或BrdU／GFAP双标细胞,但老年大鼠Brdu／NeuN双标细胞明显少于成年大鼠。结论：大鼠脑缺血激活SVZ神经干细胞增殖能力,成年大鼠明显强于老年大鼠,且新生细胞分化为神经元的比例也明显高于老年大鼠。     

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.     

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.