广防己慢性肾脏毒性及前列腺素系统异常在其中的作用

目的: 了解长期应用广防己是否可引起慢性肾脏损害及其是否与前列腺素系统异常有关。方法: 实验组正常大鼠每天给10 g/kg广防己灌胃, 对照组给等量自来水, 4周后观察肾脏病理、血肌酐(Scr)和尿素氮(BUN)、尿蛋白定量, 并测定尿、血浆及肾组织6-keto-PGF_1α和TXB₂含量。结果: 实验组大鼠出现蛋白尿、Scr和BUN升高以及肾小管细胞变性、肾间质纤维化等异常, 其尿、血浆和肾组织6-keto-PGF_1α/TXB₂均显著下降。 结论: 较大剂量和较长时间应用广防己可致肾脏损害, 前列腺素系统异常在广防己所致慢性肾脏损害的发生过程中起重要作用。     

大鼠30 min全脑缺血再灌注肾脏损伤及其机制研究

目的: 从血栓素(TXA₂)与前列环素(PGI₂)平衡失调和肿瘤坏死因子(TNF-α)的变化方面探讨老龄大鼠脑缺血再灌注肾脏损伤的发生机制。方法: 青年(5月龄)和老龄(20月龄以上)大鼠均分为模型组和正常对照组, 观察大鼠全脑缺血30 min再灌注60 min后肾脏组织形态、肾内及血浆TXB₂、6-Keto-PGF_1α和肾内TNF-α含量的变化。结果: 青年和老龄模型组大鼠肾脏组织形态均出现明显的病理改变, 且老龄较青年更为严重。青年模型组血浆TXB₂/6-Keto-PGF_1α高于青年对照组和老龄模型组, 老龄对照组高于青年对照组。青年对照组肾脏组织TXB₂/6-Keto-PGF_1α低于老龄对照组和青年模型组, 老龄模型组高于青年模型组。老龄模型组肾组织TNF水平高于老龄对照组和青年模型组。结论: 以TXA₂占优势的TXA₂与PGI₂的平衡失调及TNF的增高与大鼠脑缺血再灌注肾脏损伤有关, 老龄大鼠脑缺血再灌注肾脏损伤的病理变化更明显。     

牙髓创伤时牙髓PGE2、PGI2和TXA2浓度改变的研究

目的:探讨前列腺素与牙髓炎的关系。方法:建立大鼠创伤性牙髓炎模型,动态观察创伤后大鼠牙髓的组织学改变和检测牙髓中PGE₂,6-Keto-PGF_1α和TXB₂ 浓度的变化。结果:创伤后大鼠牙髓呈明显炎症改变,PGE₂,6-Keto-PGF_1α和TXB₂ 浓度升高,在创伤 6h后达到高峰。结论:前列腺素参与急性牙髓炎的发病。     

CD40靶向小干扰RNA抑制大鼠异体肢体移植急性排斥反应后细胞凋亡及P53、P21表达

目的探讨CD40靶向小干扰RNA（即短发夹RNA，shRNA）对大鼠异体肢体移植急性排斥反应及细胞凋亡的影响。方法以纯系SD大鼠为供体，纯系Wistar大鼠为受体，行同种异体右后肢移植。27只大鼠肢体移植后随机分为3组：实验组．注射梭华一Sofast（15μl）-siCD40—2，pSilencer（100μg）载体复合物600μl；空载体对照组，在肢体移植后，即注射Sofast（15μl）-pSilencer4．1-CMVneo（100μg）空载体复合物600μl；生理盐水对照组，在肢体移植注射生理盐水600μl。观察移植物排斥反应征象及存活情况，并于第7天对产生免疫耐受大鼠进行混合淋巴细胞反应（MLR），同时进行组织学检查。结果与其他组相比．实验组移植物发生排斥反应的时间及存活时间均显著延长（P〈0．01）（〉13d），未见排斥反应征象，其他组均于术后近期发生排斥反应；实验组大鼠对供体的淋巴细胞呈现低反应性，移植的供体同系大鼠的肢体得以存活。实验组移植物细胞凋亡率低于其他组。结论在术后不应用免疫抑制剂的情况下，CD40靶向的shRNA干扰可以抗大鼠异体肢体移植急性排斥反应。     

反义HLA-A2 cDNA抑制人成纤维细胞于大鼠脑内移植后的免疫排斥反应

为了探讨人类白细胞抗原(HLA)反义RNA在抑制异种移植免疫排斥反应中的作用,用HLA A2反义cDNA和GDNF共表达的逆转录病毒转导人胚肺成纤维细胞,再移植到Parkinson病大鼠模型纹状体(实验组);同时移植到未感染病毒的人成纤维细胞作对照。移植后每周检测大鼠旋转行为的变化;并于4d、2周、6周灌杀大鼠,进行HLA A、CD4、CD8以及人核糖核蛋白颗粒(RNP)免疫组化染色等以观察宿主的免疫排斥反应和移植物在脑内的存活情况。结果发现:两组间动物的旋转行为变化不明显。实验组HLA A阳性细胞数在移植后的各时间点均明显少于对照组(P<0.05)。移植后4d两组的CD4和CD8阳性细胞数量变化均不明显(P>0.05),CD8细胞较多。2周和6周时实验组的CD4阳性细胞均明显少于对照组(P<0.01),且随时间逐渐下降。2周后实验组的CD8细胞基本消失,而对照组的CD8水平在2周时仍较高, 6周时也可见到。实验组RNP阳性细胞数量在各个时间点都明显多于对照组(P<0.01),到6周时明显下降, 12周时完全消失。反义HLA A2cDNA可以降低异种移植引起的免疫排斥反应程度,延长移植物存活时间,但抑制长期免疫排斥反应方面仍需寻找更好的方法。     

西咪替丁对血小板功能及血栓形成的影响

目的:观察西咪替丁(Cim)对血小板功能及血栓形成的影响。方法:在体外,Cim与血小板温育后,测量血小板聚集、血小板生成丙二醛(MDA)、血小板内游离钙[Ca²⁺]_i及血栓素B₂(TXB₂)含量。用电刺激大鼠颈动脉诱导血栓形成并观察Cim的促进作用。结果:Cim使ADP诱导的血小板聚集增加,凝血酶诱导的血小板[Ca²⁺]_i、MDA升高,TXB₂下降,使电刺激大鼠颈动脉闭塞时间(OT)缩短。结论:Cim增强血小板功能,促进血栓形成。     

外源性生长抑素对正常和急性坏死型胰腺炎胰血流量的影响

目的:研究外源性生长抑素(施他宁)对正常胰腺和急性坏死型胰腺炎(ANP)胰血流量的影响及其机制。方法:以LS-Ⅲ型计算机化组织血流仪测定施他宁影响大鼠胰腺组织血流的变化、牛磺胆酸钠诱发ANP模型、放免法测定血浆二十碳烯酸类代谢物和普通病理及电镜观察。结果:正常鼠施他宁给药后胰血流量显著低于给药前;诱发ANP后,胰血流量显著降低,但施他宁+ANP组血流量显著高于ANP组;ANP组发病6h血栓素B₂(TXB₂)高于假手术对照组的4.5倍,施他宁+ANP组各时点TXB₂均显著低于ANP组,6h6-酮-前列腺素-F_1α(6-Keto-PGF_1α)及各时点TXB₂／6-Keto-PGF_1α比值则显著高于ANP组;病理观察示施他宁+ANP组腺细胞坏死积分和微血管内微血栓显著少于ANP组。结论:外源性生长抑素使正常鼠胰血流量下降,但施他宁+ANP组胰血流量显著高于ANP组,其机制可能是二十碳烯酸类异常代谢的矫正,从而改善胰组织微循环、并起细胞保护作用所致。     

CCl4诱发肝损伤过程中血浆几种花生四烯酸代谢物和激素水平动态变化的研究

目的:深入了解肝损伤对机体血浆花生四烯酸代谢、一些激素代谢以及肝脏功能变化产生的影响。方法:选用30只健康、1月龄SD大鼠,通过腹腔注射CCl₄诱发肝损伤后,第2、4、6、8周观察血浆前列腺素E₂(PGE₂)、6-酮-前列腺素F_1α(6-keto-PGF_1α)、血栓素B₂(TXB₂)、谷-草转氨酶(AST)、碱性磷酸酶(AKP)、皮质醇、胰岛素、生长激素(GH)、甲状腺素(T₄)和三碘甲腺原氨酸(T₃)水平变化。结果:在整个实验期,大鼠血浆PGE₂水平在CCl₄注射后的第2周高于对照组,TBX₂比对照组高,但二者t检验无显著性。而6-keto-PGF_1α与对照组相近;血浆AST和AKP活力分别极显著高于对照组;皮质醇和胰岛素于2、6、8周显著高于对照组;GH、T₃均于第8周显著低于对照组。T₄则于第4、6、8周显著低于对照组。结论:肝损伤影响血中花生四烯酸代谢物水平和代谢;并导致血中几种代谢激素水平的异常变化。     

输注同基因骨髓间充质干细胞联合脾组织移植诱导肝移植大鼠的免疫耐受

背景:有研究显示在免疫抑制剂的作用下,同种脾脏细胞移植可诱导免疫耐受,使移植物长期存活。另有研究还显示异种骨髓间充质干细胞移植可延长移植肝存活时间。目的:观察输注与受体同基因骨髓间充质干细胞联合脾组织移植对诱导大鼠肝移植后免疫耐受的作用。方法:将受体Lewis大鼠以数字表法随机分为4组:急性排斥组行DA-Lewis大鼠原位肝移植;环孢素A组行DA-Lewis大鼠原位肝移植后灌胃给予环孢素A;干细胞组行DA-Lewis大鼠原位肝移植,同期输注异体Lewis大鼠骨髓间充质干细胞;脾组织移植组在干细胞移植组的基础上同期移植DA大鼠脾组织。观察各组生存期,肝功能情况,血清细胞因子水平,嵌合体的形成情况及肝脏病理变化。结果与结论:与其他各组相比,脾组织移植组大鼠存活时间明显延长,术后血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素、白细胞介素2、干扰素γ水平明显降低(P0.05),白细胞介素6、白细胞介素10明显升高(P0.05),30d后受体脾脏中供体阳性细胞明显升高(P0.05)。肝脏病理显示,环孢素A组和干细胞组移植肝仅呈急性轻度排斥反应,急性排斥组呈急性重度排斥反应,脾组织移植组未见明显排斥反应。说明大鼠肝脏、脾组织移植后输注同基因骨髓间充质干细胞可减轻移植肝的排斥作用,甚至诱导免疫耐受。     

磷脂酶A2活性与慢性常压低氧性肺动脉高压关系的研究

目的:研究磷脂酶A₂(PLA₂)活性及其相关炎症介质在大鼠慢性常压低氧性肺动脉高压形成中的作用。方法:29只健康SD大鼠随机分为正常对照组、单纯低氧组和低氧加白藜芦醇苷(PD)组。右心导管法检测大鼠肺动脉压力(mPAP),观察右室/左室+室间隔比值(R/L+S)、血浆和肺匀浆中PLA₂、血栓素B₂(TXB₂)、6-酮-前列腺素F_1α(6-k-PGF_1α)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平的变化。结果:低氧3周后大鼠mPAP、R/L+S、血浆及肺匀浆中PLA₂活性、TXB₂、MDA含量显著升高;6-k-PGF_1α、SOD水平下降。用PD预处理后可减轻上述变化。结论:PLA₂通过相关炎症介质及与自由基的相互作用在慢性低氧性肺动脉高压的形成中起着重要的介导作用。     

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.