动脉血栓靶向定位的实验研究

目的:研究^99m锝标记DD单抗在动脉血栓靶向定位诊断中的应用。方法:采用外科手术的方法复制家兔股动脉血栓模型, 将^99m锝标记的抗DD单抗体注入动物体内, 以放射免疫显像检测技术观察放射性核素在血栓部位的分布。结果:^99m锝标记单抗注射后5 min, 血栓处放射性核素的分布即显著多于健侧, 10 min和30 min后, 更为明显。而单纯血管钳夹0.5-3 h均未造成^99m锝标记率升高。注射^99m锝标记单抗后, 动物未见不良反应和主要器官的病理改变。结论:^99m锝标记抗DD单抗可对实验性动物动脉血栓作出快速、准确的诊断。     

肺动脉栓塞定位诊断的实验性研究

目的： 评价［99mTc］标记的抗纤维蛋白D-二聚体单抗诊断实验性的兔肺动脉血栓栓塞的敏感性、特异性和最佳显像时间。方法： 新西兰白兔30只，分为血栓栓塞组和正常对照组，血栓栓塞组建立肺动脉血栓栓塞模型。将［99mTc］标记的抗D-二聚体单抗注入实验动物体内，以放射免疫显像技术检测放射性核素在兔双肺的分布，计算血栓栓子影像感兴趣区与对侧感兴趣区的放射性计数比值。盲法阅片并与尸检结果相对比计算诊断的敏感性和特异性。结果： ［99mTc］标记的抗D-二聚体单抗注入实验动物体内10 min和30 min后，血栓栓塞组双肺局部均出现放射性核素的浓集，血栓栓子影像感兴趣区与对侧感兴趣区放射性计数比值如下：叶动脉组为2.84±0.52、2.75±0.67，段动脉组为2.59±0.38、2.61±0.36，亚段动脉组为2.19±0.32、2.20±0.28。两位研究者独立盲法阅片，各自诊断PE的敏感性和特异性分别为76.3%、80.0%和78.9%、72.7%，联合诊断肺栓塞的敏感性和特异性分别为84.2%和80.0%。两位研究者联合阅片诊断各组肺栓塞的敏感性为：叶动脉组91%，段动脉组85.7%，亚段动脉组76.9%。结论： ［99mTc］标记抗D-二聚体单抗可对实验性兔的肺动脉血栓栓塞模型作出诊断，此法具有较高的敏感性和特异性，且具有快速、准确、无创等特点。     

~(99)Tc~m-SZ-21兔动脉血栓模型放射免疫显像研究

目的:探讨99mTc标记抗血小板板膜单克隆抗体SZ-21在兔股动脉血栓模型放免显像中的应用价值。方法:将抗体用2-IT法修饰后进行99Tcm标记;5只血栓模型兔耳缘静脉注射99Tcm-SZ-21后进行SPECT平面显像,观察血栓部位放射性分布并勾划感兴趣区(ROI),计算血栓与周围肌肉(T/M)和血栓与对侧血管(T/B)ROI比值。1只模型兔注射99Tcm-GH,作为阴性对照。结果:注射99Tcm-SZ-21后30分钟,血栓开始显影,至注射后2小时,血栓影像清晰;血栓模型活体显像时T/M和T/B比值分别为2.55±0.72和1.94±0.51,离体显像时T/B比值为4.43±1.5。结论:99Tcm-SZ-21与新鲜血栓具有较好的结合能力,靶与非靶组织比值高,能够对血栓进行早期、快速地成像。     

[125I]-(A14)单碘胰岛素在荷人肝癌裸鼠体内的趋瘤特性研究

目的：观察放射性碘标记胰岛素在荷人肝癌裸鼠体内的趋瘤或亲肿瘤（tumor-seeking）特性。方法：采用荷人肝癌裸鼠模型。用[¹²⁵I]-(A14)单碘胰岛素进行荷人肝癌裸鼠体内分布实验和抑制实验。结果：体内分布实验显示肝癌组织摄取[¹²⁵I]-(A14)单碘胰岛素明显高于本底组织（肌肉）,肿瘤与血和肿瘤与肌肉的放射性比值随时间延长而增高。体内抑制实验发现肿瘤组织于30 min的抑制率为35.0%。结论：[¹²⁵I]-(A14)单碘胰岛素在荷人肝癌裸鼠体内,通过受体介导作用,能被肝细胞癌组织特异性摄取。     

剪切力改变后动脉内皮细胞通透性的变化

目的:研究剪切力改变后内皮通透性及其超微结构。方法:饲以普通或高脂肪食的兔腹主动脉狭窄60.7%,高速摄像微粒子示踪技术血流分析,依万斯蓝和苏丹Ⅳ动脉染色,辣根过氧化物酶法电镜观察。结果:距狭窄近侧1mm的动脉前、后壁剪切力分别为74dyn/cm²和317dyn/cm²,为高剪切力区;狭窄远侧3mm前、后壁分别为-18dyn/cm²和-71dyn/cm²,为返流、涡流、湍流和停滞的低剪切力区。狭窄近、远段内皮通透性均增高,在蓝染或苏丹Ⅳ阳性区,狭窄远段内皮细胞连接部完全开放型的百分率(88.5%或88.1%)明显大于近段(22.7%或30%)(P＜0.01),远段标记HRP小胞的密度(2.57±1.14)×10¹²/m²或(2.72±1.81)×10¹²/m²明显高于近段(1.24±1.06)×10¹²/m²或(1.90±1.47)×10¹²/m² (P＜0.01)。结论:低剪切力更易导致内皮细胞对大分子物质通透性增高和动脉硬化形成。     

抑制大鼠动脉损伤后早期中膜平滑肌细胞增殖可降低内膜肥厚

目的:探讨早期中膜平滑肌细胞增殖与内膜肥厚的关系。方法:球囊导管损伤大鼠动脉后,在不同时期投予血管紧张素转换酶抑制剂(ACEI)(temocapril-HCl,10mg·kg^-1·d^-1),观察平滑肌细胞BrdU(5-溴脱氧尿嘧啶尿苷)标记率和内膜面积。结果:损伤后动脉中膜平滑肌BrdU阳性细胞出现于术后24h,BrdU标记率呈双峰期变化,第1期在1-3d,峰值在2d为5.3%,第2期在3-7d,峰值在5d为2.7%。在第1个增殖期投予temocapril显著抑制第2个增殖期的BrdU标记率(0.05±0.02)%,对照组为(4.50±0.27)%(P＜0.01),同时也显著抑制了术后10d内膜面积的增加(10670.1μm²±7713.3μm²)(P＜0.01)。而仅在第2个增殖期投药,则不能抑制内膜面积的增加(83499.5μm²±31360.0μm²)(P＞0.05),其程度与未投药组相当。结论:球囊导管损伤后动脉中膜平滑肌细胞第1个增殖期是内膜形成所必需的。     

亲和素-生物素系统介导的炎症预定位显像研究

目的：探讨亲和素-生物素系统在小鼠炎症模型中进行预定位炎症显像的实验研究。方法：实验动物均为用肌肉注射松节油所致炎症模型,采用生物素化人免疫球蛋白（B-hIgG）和99mTc标记亲和素（99mTc-Avi-din）进行二步法预定位炎症显像,在注药后3h、6h、12h对小鼠炎症模型进行显像和体内生物学分布测定,并以^99mTc-hIgG和^99mTc-Avidin作为对照组。结果：二步法预定位显像组炎症病灶在3h即可显像,其靶/非靶（T/NT）比值为1.95,6h达3.12,血中放射性清除较快。而^99mTc-hIgG组T/NT在3h仅0.38,由于其分子量较大,血中清除时间较长,血本底较高,6h-12h血中仍保持较高放射性水平,且肝脏积聚放射性较多,图像也不清晰;^99mTc-Avidin组则在肝、肾有较多放射性浓聚。结论：二步法预定位炎症显像的T/NT比值较^99mTc直接标记hIgG法为高,且病灶显像时间提前,并可提高图像的清晰度。     

TMLR对缺血心肌乳酸代谢及线粒体的影响

目的:探讨激光心肌血运重建术(TMLR)对急性心肌缺血(AMI)的作用与机制。方法: 将18条犬随机等分为假手术组、AMI组和TMLR组,采用连续型Nd:YAG激光行TMLR术。测动脉和冠状窦血乳酸含量(A.Lat 和CS.Lat),心肌乳酸代谢速率(MLR)和心肌乳酸吸收分数(MLE);超微电镜结合生物体视学原理定量观察心肌细胞线粒体形态和数量。结果: 结扎左前降支冠状动脉(LAD)后60 min,AMI组和TMLR组CS.Lat分别为(7.63±4.27)mmol/L和(5.78±3.98)mmol/L,P<0.05;MLR分别为(0.03±0.01)mmol·100 g心肌^-1·min^-1和(0.06±0.02)mmol·100 g心肌^-1·min^-1,P<0.05;MLE分别为(12.04±3.04)% 和(21.84±8.49)%,P<0.05。LAD结扎后4 h,AMI组和TMLR组线粒体体密度分别为(27.51±7.93)% 和(31.26±3.85)%,P>0.05;面密度分别为(1.25±0.18)μm^-1和(1.64±0.28)μm^-1,P<0.01;数密度分别为(0.10±0.03)μm^-3和(0.18±0.05)μm^-3,P<0.01;平均体积分别为(5.27±2.85)μm³和(2.80±0.54)μm³,P<0.05;平均外径分别为(2.06±0.36)μm和(1.78±0.12)μm,P<0.05。结论: TMLR可纠正急性心肌缺血犬的心肌乳酸代谢障碍和减轻心肌细胞损伤。     

放射性碘标记L-酪氨酸对小鼠大肠杆菌感染灶的SPECT显像

本文评价131I-L-酪氨酸能否诊断大肠杆菌感染灶和鉴别细菌感染与无菌性炎症。采用N-嗅代丁二酰亚胺法标记125I-L-酪氨酸,研究125I-L-酪氨酸与大肠杆菌的体外结合,在大肠杆菌肌肉感染模型小鼠的体内分布以及药代动力学,观察131I-L-酪氨酸在感染模型小鼠的SPECT显像。结果显示:静脉注射125I-L-酪氨酸后60min,大肠杆菌感染灶与对侧肌肉ID%/g比值是2.46倍;静脉注射131I-L-酪氨酸后1h,SPECT显像可见大肠杆菌感染灶放射性浓聚,感染灶/健康肌肉放射性比值等于2.51。无菌性炎症灶也浓聚131I-L-酪氨酸,无菌性炎症灶/健康肌肉放射性比值等于2.29。我们认为,131I-L-酪氨酸能够诊断大肠杆菌感染,但不能鉴别细菌感染灶与无菌性炎症;131I-L-酪氨酸有潜力成为炎症显像剂。     

^99mTc—HL9l肿瘤乏氧显像的动物实验

目的　用99mTc -HL91乏氧显像剂对肺腺癌小鼠模型进行体内分布和显像实验 ,以探索其对肿瘤显像的适用性 .方法　99mTc -HL91一步法标记 ,放化纯 >95 % .对 15只肺腺癌动物模型腹腔注射99mTc -HL9118 5MBq ,于 1～ 2 4小时处死取血液、肿瘤、脑、肺、心、肝、脾、肾、骨等标本称重 ,测定放射性计数 ,计算ID % /g及肿瘤组织与非肿瘤组织放射性比值 (T/NT) .同时在腹腔注射99mTc-HL91后于不同时间对模型进行静态显像 .结果　肿瘤组织对99mTc-HL91有较早较高的摄取和滞留 ,T/NT比值随时间延长而有增高趋势 .显像示肿瘤组织有较好的放射性浓聚 ,图像清晰 ,对比度良好 .结论　99mTc-HL91标记简单 ,标记率高 ,使用方便 ,在肿瘤组织中有较好的摄取与滞留 ,是一种良好的肿瘤乏氧显像剂 ,但需要进一步研究其机理和改进方法 ,提高T/NT比值 ,以开展临床试验     

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.     

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 case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

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.