低温保存同种异体带瓣主动脉移植的免疫反应

背景:前期研究证实,液氮低温保存同种异体主动脉能保持其细胞的生物活性和组织结构的完整性,但有关同种异体带瓣主动脉移植的排斥反应研究较少。目的:观察同种异体带瓣主动脉移植后移植物的免疫指标变化特点。方法:将低温保存的SD大鼠带瓣主动脉异位植入Wistar大鼠腹主动脉,分组干预:同种异体移植组不进行干预;免疫干预组移植后给予环孢素A;对照组为假移植,将腹主动脉切断后直接吻合。移植后1,2,3,4,5周收集移植动物血清标本,免疫组织化学染色测量MHCⅡ阳性表达,淋巴细胞涂片免疫组织化学测定CD4+、CD8+百分率;应用酶联法测定血清中白细胞介素2,肿瘤坏死因子α水平。结果与结论:同种异体主动脉移植后1～4周可见MHC显著阳性,CD4+、CD4+/CD8+比值明显增高,血清中白细胞介素2和肿瘤坏死因子α水平明显增高,并在移植后5周内维持较高水平,与对照组比较差异有显著性意义(P0.05)。环孢素A对同种异体主动脉移植物内膜增厚、淋巴细胞浸润、MHCⅡ表达、T淋巴细胞激活、白细胞介素2和肿瘤坏死因子α水平的增高具有明显抑制作用(P0.05)。说明低温保存同种异体主动脉移植后有明确的免疫排斥反应发生,环孢素A对同种异体移植后的免疫排斥反应有明显抑制作用。     

伴有高血压的糖尿病大鼠主动脉的结构重建

目的 :观察伴有高血压的糖尿病 (SHRDM)主动脉结构重建的规律 ,并探讨高血糖、高血压对其影响。方法 :STZ诱导SHR大鼠建立SHRDM实验动物模型 ,。观测主动脉血管壁中膜结构成分的改变。结果 :SDDM(有高血压的糖尿病 )大鼠自 4周始主动脉中膜平滑肌相对含量和核密度、胶原纤维相对含量均大于SD组 ,弹性纤维相对含量少于SD组。SHRDM组主动脉平滑肌相对面积、C/E值大于SD和SHR组 ,但SMC核数少于SDDM ,多于SHR。结论 :糖尿病早期已出现主动脉结构重建 ,以平滑肌增生为主 ;高血压使平滑肌细胞肥大为主 ,因而SHRDM增生、肥大共存。高血压、高血糖均显著影响主动脉结构重建 ,高血压影响大于高血糖。     

腹主动脉缩窄法致大鼠心肌纤维化模型的建立

目的用腹主动脉缩窄法建立大鼠心肌纤维化模型。方法16只雄性SD大鼠随机分为腹主动脉缩窄组（模型组）及假手术组。分别比较两组左室心肌质量指数、左室心肌病理形态HE染色及左室心肌胶原染色等指标造模4周及造模8周时的变化。结果模型组造模4周及8周时左室重量指数（LVMI）较假手术组显著升高（P〈0.05）。胶原染色、HE染色及超微结构等病理变化,模型组造模4周、8周较假手术组改变明显;假手术组4周及8周时基本一致。结论SD大鼠在腹主动脉缩窄术后4周即可达心肌纤维化模型。     

体液免疫在异品系大鼠腹主动脉移植硬化中的作用

目的： 探索体液免疫在移植动脉硬化演变过程中的作用。方法: 建立大鼠腹主动脉移植硬化模型，HE染色和光镜下检查植入的腹主动脉病理学改变，计算机图像分析系统自动测出其管腔面积、内膜面积和中膜面积。间接免疫荧光法检测植入的腹主动脉壁IgG、IgM、C3沉积情况。结果: 异品系移植组术后60 d腹主动脉管腔明显缩小，内膜显著增厚，中膜变薄。增生的腹主动脉内膜主要由单核/巨噬细胞和平滑肌细胞构成，中膜层平滑肌细胞坏死，数量减少，弹力膜断裂。IgM、C3在术后各组各时点动脉壁上均未见沉积现象。IgG在异品系移植组术后7 d、15 d时动脉中膜层呈强荧光沉积，30 d后IgG荧光消失。结论: 体液免疫因子IgG可能参与了异品系大鼠移植腹主动脉硬化的过程。     

ApoCⅢ转基因引起的高血浆甘油三酯对弹力蛋白酶诱导的LDLR-/-小鼠腹主动脉瘤的影响

 目的: 研究载脂蛋白CⅢ(ApoCⅢ)转基因引起的高血浆甘油三酯(TG)对腹主动脉瘤发生发展的影响。方法: 以LDLR^-/-和ApoCⅢ⁺LDLR^-/-小鼠喂饲高脂饲料,分别造成高胆固醇血症和高胆固醇合并高甘油三酯血症模型;采用弹力蛋白酶法在2种基因型小鼠上诱导建立腹主动脉瘤模型;以动脉瘤发生率、动脉瘤直径、主动脉弹力板降解情况及血管基质金属蛋白酶的表达等为指标,比较LDLR^-/-和ApoCⅢ⁺LDLR^-/-小鼠分别在普通饲料和高脂饲料喂饲条件下,腹主动脉瘤的发生和发展情况;采用TNF-α诱导血管平滑肌细胞(VSMC)建立动脉瘤体外微环境模型,研究来自具有正常含量ApoCⅢ或高含量ApoCⅢ小鼠的富含甘油三酯的脂蛋白(TRLs)对弹力蛋白表达的影响。结果: 高脂饲料加重了LDLR^-/-小鼠的腹主动脉瘤程度;高脂饲料喂饲的ApoCⅢ⁺LDLR^-/-小鼠腹主动脉瘤轻于高脂喂饲的LDLR^-/-小鼠;在体外,TRLs具有抑制TNF-α诱导的VSMC弹力蛋白酶降解的作用,且来自高含量ApoCⅢ小鼠的TRLs对弹力蛋白降解的抑制作用更为显著。结论: ApoCⅢ转基因引起的高血浆甘油三酯能减轻弹力蛋白酶诱导的LDLR^-/-小鼠的腹主动脉瘤,该作用可能与ApoCⅢ基因及其导致的高血浆甘油三酯有关。     

免疫抑制剂降低同种带瓣主动脉移植后钙含量的观察

探讨在同种带瓣主动脉移植后早期使用免疫抑制剂降低钙含量的机制和效果。成年SD大鼠为供体;Wistar大鼠为受体,行同种异体带瓣主动脉腹主动脉的异位移植,实验组移植后给予环孢素A(CsA)15mg/kg·d,共2周。对照组不做任何处理。同基因组行同一种系的近交系大鼠同种带瓣主动脉移植。各组随机分为5组,每组8只,分别于术后2、4、8、12、16周使用流式细胞仪测定大鼠CD25、CD71的表达,移植物进行光镜和电镜观察,免疫组化测定CD40的表达,同时测定钙含量。对照组移植后CD25、CD71和CD40表达的高峰时间段主要在移植后早期(2～4周),此后的表达水平逐渐回落,12周后维持在低水平。CsA组在移植后2～4周CD25、CD71和CD40的表达明显低于对照组(P<0.01),但是在8周后的表达水平与对照组无差别(P>0.05)。对照组的钙含量从4周开始升高,随着时间的推移,逐渐升高,在12周达到高峰,此后进入平台期。CsA组在移植后4、8、12、16周4个不同时间点的钙含量显著低于对照组(P<0.01)。移植后早期,实验组的内皮细胞脱落和平滑肌细胞的坏死情况较对照组减轻。同种瓣移植后早期使用免疫抑制剂具有抗钙化作用,其机制在于抑制移植后早期的免疫排斥,减轻了内皮细胞和平滑肌细胞所受到的免疫攻击,保护了内皮细胞和平滑肌细胞;但是否能改善同种瓣功能和血流动力学尚需进一步观察。     

伴有高血压的糖尿病大鼠腹主动脉结构重建

用链服佐菌素（streptozotocin,STZ）分别诱导SD和自发性高血压大鼠（Spontaneouslyhypertensiverats,SHR）,建立伴有（SHRDM）和不伴有（SDDM）高血压的糖尿病动物模型,以SHR大鼠为高血压对照,SD大鼠为正常的对照组,每组再分为1、48、16、24周5个时相点,每个时相点5只动物。用图像分析系统对各组动物的腹主动脉中膜显微结构成分进行研究。结果显示,随糖尿病病程的增加,平滑肌、胶原纤维相对含量增加,C／E值增大,弹性纤维减少,其中平滑肌相对含量的增加出现早,4周时即出现的明显差异（P＜0．05）。平滑肌细胞核个数…     

不同原因诱导大鼠腹主动脉移植硬化的组织病理比较

目的：研究不同原因诱导的大鼠腹主动脉移植硬化的组织病理学改变。方法：140只大鼠随机分组：A组为非移植组,B组为同品系移植缺血小于30min组;C组为同品系移植缺血4h组;D组为异品系移植缺血小于30min组,术后7,15,30,60天切取植入的腹主动脉进行光镜,电镜检查。结果：移植7－15天时C组动脉内膜有多量多形粒细胞和单个核细胞粘附,浸润,电镜检查多形核粒细胞为中性粒细胞,而D组移植动脉各层均有大量的淋巴细胞浸润,移植30－60天时C组,D组移植动脉内膜均有显著增厚,增生的内膜均由单核／巨噬细胞和平滑肌细胞构成,但前者无中膜层平滑肌坏死及弹力膜断裂现象。结论：中性粒细胞在缺血／再灌注损伤诱导的同品系大鼠腹主动脉移植硬化发挥了重要作用,其机制值得进一步研究。     

大鼠"二袖套"法双重灌注全血供肝移植模型的建立

目的：建立一个供肝灌注良好受体无肝期明显缩短及移植肝全血供稳定的肝移植动物模型。方法：“二袖套”法在Kamada吻合血管基础上改良,供肝分别经腹主动脉和门静脉双重全肝脏灌注;受体肝脏分步切除,肝上下腔静脉采用缝合法吻合,门静脉和肝下下腔静脉分别用袖套法吻合。移植肝脏动脉重建采用单纯血管套入式吻合或血管缝合的方法,胆总管采用单管内支架胆管端端吻合法。结果：共施行全血供大鼠原位肝脏移植76例（不包括预试验）,手术成功率93．406,1周存活率86．8％。结论：娴熟的显微外科技术、有效改良措施和注重手术细节是手术成功的保障,良好的灌注、受体无肝期的缩短及重建移植肝脏动脉血供能有效提高动物模型的稳定性。     

内源性硫化氢抑制高肺血流大鼠肺动脉弹力蛋白的表达

目的探讨内源性硫化氢(H2S)对高肺血流所致肺血管重构大鼠肺动脉弹力蛋白的调节作用。方法将雄性SD大鼠随机分为4组:分流组、分流 炔丙基甘氨酸(PPG)组、假手术组和假手术 PPG组,每组8只。分流组及分流 PPG组大鼠经腹主动脉-下腔静脉穿刺建立高肺血流动物模型。4周后,测定大鼠肺动脉平均压(mPAP),显微镜下观察肺血管结构变化;用免疫组化方法测定α-平滑肌肌动蛋白(α-SM-actin)、弹力蛋白、转化生长因子-β(TGF-β)和结缔组织生长因子(CTGF)在肺动脉平滑肌细胞的表达。结果分流 PPG组mPAP较分流组和假手术组明显升高(P<0.05);在分流组,小型肺动脉中肌型动脉和部分肌型动脉所占百分比明显高于假手术组(均P<0.05),非肌型动脉所占百分比明显低于假手术组(P<0.01);在分流 PPG组,小型肺动脉中肌型动脉所占百分比明显高于分流组(P<0.01),非肌型动脉所占百分比明显低于分流组(P<0.01)。分流组肺中,小型肺动脉平滑肌细胞α-SM-actin、弹力蛋白、TGF-β和CTGF含量明显高于假手术组(均P<0.01),分流 PPG组上述指标明显高于分流组(均P<0.01)。结论内源性硫化氢可能通过抑制高肺血流大鼠肺动脉弹力蛋白的表达,调节其肺血管结构重构。     

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.