斯钙素1基因在二乙基亚硝胺诱发大鼠肝癌发生中的表达

目的 检测哺乳动物斯钙素1(STC1) mRNA和STC1蛋白在二乙基亚硝胺(DENA)诱导大鼠肝癌发生不同阶段的表达水平. 方法 选取80只SD大鼠,随机分为两组,实验组按DENA 70 mg/kg体重灌胃,诱导大鼠肝癌模型,对照组等量蒸馏水灌胃.采用组织病理学、RT-PCR和Western blotting技术分析大鼠肝组织中的STC1基因和蛋白表达水平. 结果只有在DENA诱导的大鼠肝癌组织内才有STC1 mRNA表达和STC1分泌,并且与肝癌发生进程具有相关性. 结论 STC1基因表达和STC1分泌水平与肝细胞癌变具有相关性,可望成为用于肝癌诊断的分子标记物.     

HGF、IL-6在实验性早期肝癌中的表达及其诊断意义

目的：探讨肝细胞生长因子（HGF）、白细胞介素－6（IL－6）在实验性早期肝癌中的诊断意义。方法：用ELISA、免疫组化、免疫电镜方法分别检测HGF及IL－6在实验组及正常对照组的血清水平和在肝细胞中的表达情况，用免疫细胞化学方法检测HGF在人肝细胞系中的表达。结果：HGF、IL－6在肝癌旁组织肝细胞质中表达阳性。肝癌组织中表达均下降，人肝癌细胞系中HGF强阳性表达，实验组HGF、IL－6血清含量显著高于正常对照组（P＜0．01）。结论：化学致癌剂诱发实验性早期肝癌过程中、IL－6可能是激活HGF的细胞因子，HGF以自分泌机制发挥促肝细胞增殖的效用。HGF、IL－6有望成为早期肝癌的诊断指标。     

仙灵骨葆胶囊对骨质疏松症大鼠BMP-2、BMP-4、TGF-β1和PKC蛋白表达影响

目的探讨仙灵骨葆胶囊对骨质疏松症大鼠骨形成蛋白-2(BMP-2)、骨形成蛋白-4(BMP-4)、转化生长因子β1(TGF-β1)和蛋白激酶C(PKC)蛋白表达影响。方法 40只SD大鼠随机分为假手术组、模型组、对照组和实验组,每组大鼠10只。假手术组给予等剂量生理盐水灌胃;模型组:给予等剂量生理盐水灌胃;对照组:给予盖天力牡蛎钙0.3 g/kg灌胃;实验组:给予仙灵骨葆胶囊0.4 g/kg灌胃。各组大鼠灌胃均为每日1次,连续灌胃8周。采用双能X线骨密度仪检测股骨和腰椎骨密度;采用ELISA法检测血清Ca和P含量;采用免疫组化法检测骨组织BMP-2、BMP-4、TGF-β1和PKC蛋白表达。结果除假手术组,其余各组大鼠均造模成功。模型组、对照组、实验组股骨和腰椎骨密度低于假手术组(P0.05);对照组、实验组股骨和腰椎骨密度高于模型组(P0.05);实验组股骨和腰椎骨密度高于对照组(P0.05)。模型组、对照组、实验组血清Ca和P含量低于假手术组(P0.05);对照组、实验组血清Ca和P含量高于模型组(P0.05);实验组血清Ca和P含量高于对照组(P0.05)。模型组、对照组、实验组BMP-2、BMP-4和PKC蛋白表达高于假手术组,而TGF-β1蛋白表达低于假手术组(P0.05);对照组、实验组BMP-2、BMP-4和PKC蛋白表达低于模型组,而TGF-β1蛋白表达高于假手术组(P0.05);实验组BMP-2、BMP-4和PKC蛋白表达低于对照组,而TGF-β1蛋白表达高于对照组(P0.05)。结论仙灵骨葆胶囊可增加骨质疏松症大鼠骨密度,认为可能与下调BMP-2、BMP-4和PKC蛋白表达及上调TGF-β1蛋白表达相关。     

姜黄素对miR-21靶控的信号转导蛋白K-ras的影响

目的：探讨姜黄素对miR-21靶控的信号转导蛋白K-ras的影响。方法18只SD雄性大鼠,随机分为对照组、模型组和姜黄素组,每组6只。除对照组外,模型组和姜黄素组用二乙基亚硝胺( DENA)连续灌胃18周,姜黄素组于第9周用姜黄素灌胃,每周2次,连续10周;对照组先用生理盐水灌胃8周,9~18周用生理盐水+0．5%羧甲基纤维素钠灌胃。应用qRT-PCR技术检测miR-21的表达;Western blot法检测K-ras蛋白的表达。结果肝癌模型组miR-21基因的相对表达量较正常对照组明显增加( P<0．05);姜黄素组miR-21基因相对表达量较肝癌模型组明显降低( P<0．05),与对照组相比表达量增加,差异有统计学意义( P<0．05);与对照组相比,模型组和姜黄素组肝癌组织中K-ras蛋白相对表达量均明显升高(P<0．05),姜黄素组大鼠肝癌组织中K-ras蛋白相对表达量较模型组均明显降低( P <0．05)。Pearson相关分析显示,实验各组K-ras蛋白及miR-21的表达量均呈正相关( P<0．05)。结论姜黄素可能通过调控miR-21靶控的信号转导子K-ras蛋白表达促进肝癌的发生、发展及侵袭转移,对肝癌生物靶向治疗及预后判断具有潜在临床应用价值。     

姜黄素对gp120所致大鼠学习记忆障碍的作用及机制研究

目的:探讨姜黄素改善HIV-1包膜糖蛋白gp120所致大鼠学习记忆障碍的作用及机制.方法:用gp120侧脑室灌注制备拟艾滋痴呆症动物模型,并用水迷宫实验观察侧脑室灌注gp120造成的大鼠认知功能的障碍. SD大鼠随机分为6组:对照组、假手术组、模型组、姜黄素低、中和高剂量治疗组.除对照组、假手术组外其余4组侧脑室缓慢注射5 μL的gp120,连续3 d.第4天开始,姜黄素低、中、高剂量治疗组分别给予50 mg/(kg·d)、100 mg/(kg·d)、200 mg/(kg·d)的姜黄素灌胃,对照组、假手术组和模型组大鼠用双蒸水灌胃,连续灌胃14 d.然后各组大鼠进行水迷宫测试,并分组进行NMDA2B受体免疫组化染色.结果:50 ng/d的gp120侧脑室灌注3 d,可制备拟艾滋痴呆症动物模型. Morris水迷宫可见模型组大鼠逃避潜伏期与对照组相比明显延长(P<0.05),姜黄素低、中、高剂量治疗组大鼠的逃避潜伏期与模型组相比缩短,其中姜黄素低剂量组效果更好(P<0.05).免疫组化结果显示模型组大鼠海马内N-甲基天冬氨酸受体(NMDA2B)的表达与对照组相比有所降低(P<0.01),姜黄素各剂量治疗组NMDA2B受体的表达与模型组相比有所上调.结论:gp120侧脑室灌注可制备拟艾滋痴呆症动物模型,姜黄素具有改善侧脑室灌注gp120所致大鼠学习记忆障碍的作用,其机制可能与对抗NMDA2B受体表达下调有关.     

银杏叶提取物对铝盐诱导大鼠脑功能失调模型的保护作用

目的 :观察银杏叶提取物 (GbE)对铝盐诱导的脑功能失调大鼠模型学习记忆的影响 ,并探索其作用机制。方法 :Wistar大鼠每天灌胃AlCl35 0 0mg·kg 1一月 ,饮用 1 .6g·L 1的AlCl3溶液到第五月 ,Morris水迷宫检测空间学习记忆能力 ,化学比色法检测血清中的乙酰胆碱酯酶 (AChE)活性 ,免疫组化法检测海马AChE的表达 ,并用BI2 0 0 0图象分析系统定量分析。结果 :铝明显延长大鼠逃避潜伏期搜索距离 (P <0 .0 1 ) ,预示脑功能失调 ;GbE(5 0～ 2 0 0mg·kg 1·d 1,i.g)明显缩短铝盐诱导的大鼠大鼠逃避潜伏期搜索距离(P <0 .0 1 ) ;剂量依赖…     

黄曲霉毒素B_1诱发大鼠肝脏癌变机理的实验研究Ⅱ——肝癌形成过程中肝细胞及肝癌细胞超微结构的改变

本文着重讨论AFB_1诱发大鼠肝癌形成过程中肝细胞超微结构的改变;AFB_1作用肝细胞发生癌变的机理;AFB_1和化学致癌剂诱发大鼠肝癌的区别;AFB_1诱发大鼠肝癌的转归。材料和方法本文所用Wister大鼠实验及其分组情况见邵氏报道。实验开始后,每月处死一次,自45周起改为半个月一次,每次实验组5只,对照组各1只,处死或自然死亡的大鼠迅速剖腹取新鲜肝组织,按癌周,癌     

维生素E对慢性染镉肝细胞凋亡的拮抗作用

目的　探讨维生素E(vitaminE ,VE)对慢性染镉肝细胞凋亡的拮抗作用。方法　健康昆明种小鼠 75只 ,体重 2 8g～ 32g ,随机分 3组 :染镉组 (Cdcl2 2mg·kg-1,皮下注射 ,每周 2次 ,共 3个月 )、VE +镉组 (染镉同时给VE 10mg·kg-1·d-1,灌胃 )、正常对照组 (注射等量生理盐水 )。采用免疫组化细胞凋亡染色 (Tunel法 )结合形态计量分析 ,观察 3组小鼠肝细胞凋亡的形态和数量改变。结果　 (1)染镉组小鼠肝细胞可见较多的细胞凋亡 ,VE +镉组肝细胞凋亡数量较少 ;细胞计数表明 ,VE +镉组细胞凋亡数量比染镉组明显减少 (P <0 0 1) ,而与正常对照组相比无显著性差异 (P >0 0 5 )。 (2 )凋亡肝细胞主要有以下形态特点 :①细胞胞体变小 ;②细胞核核仁消失 ,染色质浓缩边集于核膜下 ,核呈环状 ,晚期核固缩、变小 ,深染、致密度高。形态计量分析表明 ,凋亡肝细胞核的平均截面积、平均表面积、平均截面周长、体积密度等形态参数值均较正常肝细胞核明显减小 ,有显著性差异 (P <0 0 1) ;③核碎裂 ,形成凋亡小体。结论　VE对镉所致的肝细胞凋亡有抑制作用。     

丝胶对Ⅱ型糖尿病大鼠肝胰岛素受体和胰岛素受体底物-2的调控作用

目的:研究丝胶对Ⅱ型糖尿病大鼠肝细胞胰岛素受体(IR)及胰岛素受体底物-2 (IRS-2)表达的影响.方法:SD大鼠随机分为5组,分别为正常对照组、糖尿病模型组、丝胶治疗组、阳性对照组、丝胶预防组.采用链脲佐菌素连续腹腔注射法制作Ⅱ型糖尿病大鼠模型.丝胶治疗组大鼠给予丝胶(2.4g·kg-1·d-1)灌胃35 d,阳性对照组大鼠给予二甲双胍(55.33 mg·kg-1·d-1)灌胃35 d,丝胶预防组大鼠于2％链脲佐菌素(25 mg/kg)连续腹腔注射之前给予丝胶(2.4g·kg-1·d-1)灌胃35d.采用葡萄糖氧化酶法检测各组大鼠的空腹血糖;SP免疫组织化学显色、蛋白免疫印迹和RT-PCR检测肝细胞中IR和IRS2的表达.结果:丝胶可明显上调糖尿病大鼠肝胰岛素受体和胰岛素受体底物-2mRNA表达,显著增加IR和IRS-2蛋白的表达.结论:丝胶可通过上调糖尿病肝IR和IRS-2的表达,改善胰岛素抵抗,起到降低血糖的作用.     

胚胎干细胞移植对转化生长因子β1和髓鞘碱性蛋白影响

背景:多项研究证实胚胎干细胞诱导的神经前体细胞能够促进脊髓损伤大鼠功能的恢复。目的:观察胚胎干细胞经体外诱导培养的神经前体细胞在脊髓损伤大鼠中的作用。方法:144只大鼠随机分为3组,实验组和对照组建立大鼠脊髓全横断模型,实验组造模后在椎管内损伤区上下两端注射胚胎干细胞衍生细胞;对照组于相同部位注射PBS;假手术组仅行椎板切除,不损伤脊髓,不做其他处理。结果与结论:对照组和实验组大鼠造模后21 d后,对照组脊髓损伤区域转化生长因子β1表达显著高于实验组(P0.05)。各时间点实验组大鼠脊髓中髓鞘碱性蛋白表达量显著高于对照组(P0.05)。细胞移植后各时间点实验组BBB评分明显优于对照组(P0.05)。提示胚胎干细胞培养诱导分化为神经前体细胞移植后期可降低转化生长因子β1的表达,并可以提高髓鞘碱性蛋白的表达变化,有助于大鼠全横断脊髓损伤的恢复。     

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.