川芎嗪对自体移植内皮祖细胞修复兔受损腹主动脉内膜的影响

目的通过在体实验研究川芎嗪对内皮祖细胞（EPCs）修复球囊损伤后的兔腹主动脉的影响,探讨更好的损伤性血管修复的方法。方法密度梯度离心法分离兔外周血单个核细胞,以EBM-2培养基培养7d,获得兔外周血内皮祖细胞,应用2．5F球囊导管造成兔腹主动脉去内皮损伤模型。将实验兔分为三组,每组6只,对照组使用生理盐水,EPCs组只使用EPCs,EPCs＋川芎嗪组注射EPCs及川芎嗪,术后14d处死动物,并测量各组内膜损伤血管再生内皮覆盖率和新生内膜增生程度。结果EPCs＋川芎嗪组新生内膜／中膜厚度明显低于EPCs组,新生内膜面积明显高于EPCs组,两组均与对照组相比差异有统计学意义。结论EPCs可促进受损血管内膜修复,川芎嗪具有增强EPCs修复血管内膜的作用。     

自体内皮细胞移植在损伤动脉再内皮化及抑制新生内膜增生中的作用

目的:观察自体内皮细胞移植在损伤动脉血管再内皮化及抑制新生内膜增生中的作用。方法: 30只健康雄性纯种新西兰兔行双侧髂股动脉球囊损伤,一侧于损伤后立即经球囊导管行自体静脉内皮细胞移植,另一侧行培养基对照。其中10只动物分别于术后4 h、4 d处死,行扫描电镜检查;5只动物,先将细胞用荧光标记物标记后,再移植入体内,4 d后进行荧光示踪检查;5只动物于术后4 d行Evans blue染色,观察内皮损伤血管段再内皮化情况;其余动物于术后28 d处死,行病理学分析。结果:细胞移植术后4 h,对照组见整个内皮层剥脱,暴露出内皮下弹力膜及平滑肌,细胞移植组则见部分移植内皮已粘附在内皮剥脱血管壁,细胞呈圆形,但尚未铺展;细胞移植术后4 d,移植的内皮已变形,在内皮剥脱血管壁铺展成单层,大量荧光标记内皮细胞被覆在损伤动脉血管内膜;对照组损伤血管几乎完全被Evans blue染成蓝色,细胞移植组损伤血管则60%不被Evans blue着染;病理学分析发现细胞移植组新生内膜面积、最大动脉内膜厚度均显著少于对照组。结论: 自体内皮细胞能有效地经球囊导管移植到内皮损伤血管段,并有减轻新生内膜增生的作用。     

小鼠血管内皮损伤/再生伴内膜增生模型的建立

目的： 探讨如何建立稳定的小鼠血管内皮损伤/再生及内膜增生模型。方法： 用改良的空气干燥法造成小鼠颈总动脉内皮剥脱损伤模型。术后活体灌注Evans蓝染料以评估受损内皮再生情况，并取受损部分动脉作纵向切片，行CD31内皮细胞标志抗原检测。术后4周常规组织学检测内膜增生肥厚情况。结果： 内皮损伤术后内皮完全剥脱，Evans蓝染色完全，未见CD31抗原表达，随着术后时间延长，Evans蓝染色部分从损伤边缘开始，逐渐向中心区缩小，CD31抗原表达逐渐增多。术后7 d仍可见部分损伤血管未再内皮化。术后4周可见明显新生内膜增生。结论： 用改良的空气干燥法可以建立稳定的小鼠动脉内皮损伤/再生模型，并且伴有明显的新生内膜增生。     

粒细胞集落刺激因子对大鼠颈动脉球囊损伤后再内皮化和内膜增生过程的影响

目的：探讨重组人粒细胞集落刺激因子对大鼠颈总动脉球囊损伤后再内皮化和内膜增生过程的影响。方法:56只Wistar大鼠随机分为2组,重组人粒细胞集落刺激因子（商品名：瑞白）+损伤组（rhG-CSF预防组）(n=28):皮下注射瑞白30 μg/kg，每日1次，共7 d后，行左颈总动脉球囊拉伤,术后1 h（n=4）、3 d(n=4)、5 d(n=4)、7 d(n=5)、14 d(n=6)取材;生理盐水+损伤组(NS+损伤组)(n=28):皮下注射生理盐水0.5 mL,同上时点取材。应用扫描电镜、伊文氏蓝染色、HE染色、免疫组织化学的方法,观察颈总动脉损伤后再内皮化、新生内膜增厚及细胞增殖的情况。通过RT-PCR检测血管壁内皮型一氧化氮合酶（eNOS）mRNA表达。结果:重组人粒细胞集落刺激因子可明显增加损伤血管内皮的修复面积、抑制新生内膜形成，增加了血管壁eNOS mRNA表达 。结论：重组人粒细胞集落刺激因子对大鼠颈总动脉球囊损伤血管再内皮化和内膜增生过程有血管重塑作用。     

四逆汤对兔髂动脉球囊损伤病变区TGF-β1表达的影响

目的:通过球囊损伤兔髂动脉造成动脉损伤的模型，观察四逆汤对损伤后动脉内膜的保护和修复作用以及对转化生长因子β1（TGF-β₁）的影响。 方法:雄性新西兰兔24只，随机分为对照组、模型组、四逆汤治疗组（四逆汤组），每组8只。对照组给予普通饲料，模型组和四逆汤组给予高脂饮食。饲养2周后模型组、四逆汤组兔行髂动脉内膜剥脱术。术后4周处死各组实验兔，采用ELISA方法检测血清TGF-β₁水平；HE染色观察髂动脉内膜增生情况，通过免疫组化观察TGF-β₁蛋白在血管壁的表达；采用RT-PCR方法检测血管壁TGF-β₁ mRNA的表达。 结果:病理观察可见对照组兔髂动脉管腔和管壁厚度正常，管壁光滑；模型组的管壁明显增厚、管腔明显狭窄，内膜增厚；而治疗组管壁增厚较轻，管腔狭窄较轻，内膜增厚程度减轻。对照组兔血清TGF-β₁水平明显低于模型组和四逆汤组，四逆汤组又明显低于模型组（P<0.05）。免疫组化发现对照组兔髂动脉内膜TGF-β₁的染色灰度和染色阳性面积比明显小于模型组和四逆汤组，而四逆汤组TGF-β₁的染色灰度和染色阳性面积比明显小于模型组（P<0.05）。对照组兔髂动脉TGF-β₁ mRNA表达明显低于四逆汤组和模型组，而四逆汤组TGF-β₁ mRNA的表达少于模型组（P<0.05）。 结论:四逆汤可减轻兔髂动脉剥脱术后的内膜增生和血管的狭窄, 其机制可能与抑制髂动脉损伤后内膜TGF-β₁的基因和蛋白的表达，减少TGF-β₁的产生有关。     

氟伐他汀抑制球囊损伤后兔的血管内膜增殖

目的：探讨兔髂动脉急性损伤后，氟伐他汀对血管内膜增殖的抑制作用及机制。 方法： 给新西兰大耳白兔行右髂动脉球囊导管内膜剥脱术，术后灌胃予氟伐他汀（8 mg·kg-1·d-1）治疗28 d，术前、术后3 h及3 d用放射免疫法测定血清中内皮素-1、血栓素A2和前列环素浓度；28 d后HE染色观察血管内膜增生情况，免疫组织化学方法检测细胞外基质的变化。结果： ① 兔髂动脉急性损伤后血清内皮素-1及血栓素A2浓度即明显增加，前列环素水平则显著下降；氟伐他汀治疗显著抑制内皮素-1和血栓素A2的升高；提高血清前列环素的水平；② 氟伐他汀治疗减轻了内膜TGF-β1的过度表达及细胞外基质（FN、LN）的沉积；③ 氟伐他汀显著抑制了内膜的增殖和肥厚。结论：氟伐他汀治疗抑制血管损伤后血栓的形成，减轻了内膜的增殖及内膜中细胞外基质的沉积。     

兔动脉粥样硬化血管成形术后再狭窄模型的建立与改良*

 目的：探讨建立兔动脉粥样硬化血管成形术后再狭窄模型的有效方法。方法：30只雄性新西兰大白兔,随机分成3组,即空白对照组、下肢动脉切开组及下肢动脉穿刺组,每组10只。空白对照组仅行高脂饲料喂养,另外2组高脂饲料喂养1周后行下肢动脉穿刺或切开行髂动脉内膜剥脱术,继续高脂饲料喂养4周,下肢动脉穿刺组再次穿刺股动脉行髂动脉球囊成形术,下肢动脉切开组经颈动脉切开行髂动脉球囊成形术。3组均普通饲料喂养4周,计算每天进食饲料量,采血化验血脂,取病变段血管行苏木精-伊红染色及图像工作站对血管造影结果行血管狭窄分析。结果：下肢动脉切开组进食饲料量减少,血清总胆固醇和低密度脂蛋白胆固醇显著低于对照组。3组动物均出现下肢动脉粥样硬化,其中下肢动脉穿刺组及下肢动脉切开组内膜显著增厚,管腔狭窄。动脉穿刺组与动脉切开组血管面积狭窄率及直径狭窄率与对照组相比差异显著(P<0.01)。结论：下肢动脉穿刺与球囊损伤、球囊血管成形术结合可成功建立兔动脉粥样硬化血管成形术后再狭窄模型,方法简单,可重复性强,较下肢动脉切开术更适合血管成形术后再狭窄模型的建立。     

中药赤芍对球囊损伤术后血管重构的干预研究

目的 观察中药赤芍防止球囊损伤术后血管重构作用。方法 新西兰白兔随机分为对照组、单纯高脂组、赤芍高剂量组、低剂量组。高脂喂养6周建立动脉粥样硬化模型,行颈动脉球囊损伤术,8周时取材作病理形态学检查。结果(1)与高脂组比较,赤芍高、低剂量组增生内膜面积、中层面积,内膜、中膜、外膜PCNA阳性着色均显著减少(P<0.05或P<0.01)。(2)各组内皮增生成分主要为平滑肌细胞;巨噬细胞阳性着色主要分布在外膜,与高脂组比较,赤芍高、低剂量组阳性着色较少。(3)高脂组动脉损伤侧外膜Ⅰ型胶原增多,赤芍组Ⅰ型胶原增加较少。结论 赤芍对高脂喂养兔颈动脉球囊损伤术后血管重构有显著防止作用。     

转染VEGF165基因抑制兔动脉损伤后内膜增生

目的：观察局部转染血管内皮生长因子165（VEGF165）基因对损伤动脉内膜增生的影响并探讨可能机制。 方法： 采用显微外科手术方法，建立兔右髂外动脉损伤模型。将105只新西兰大白兔随机分为3组，每组35只。A组为生理盐水对照组，B组为脂质体介导的pBudCE4.1转染组，C组为脂质体介导的pBudCE4.1/VEGF165转染组。用微注射器将各种转染液注入损伤的血管壁，每组按实验终点（术后2、3、7、14和28 d）分为5个亚组，每个亚组7只兔。于术后各实验终点，取损伤段的血管用于病理组织学检查、电镜观察、RT-PCR和免疫组化染色检查。 结果： 术后各时点C组血管内膜厚度和内膜面积均显著小于A组和B组（P<0.01），术后28 d时C组管腔狭窄率平均比A组和B组低51.6%和49.8％。术后各时点C组血管壁的VEGF165基因的mRNA表达量和血管壁VEGF165阳性细胞率明显高于A组和B组（P<0.01）。C组血管壁血管内皮细胞（VEC）修复和生长增殖速度明显快于A组和B组。A组和B组间无明显差异。 结论： 局部转染VEGF165基因可抑制血管新生内膜增生及血管再狭窄，为将来血管内膜增生的基因治疗奠定基础。     

全反式维甲酸对大鼠腹主动脉球囊损伤后内膜增生和血管重塑的影响

目的：研究全反式维甲酸（ATRA）对球囊损伤大鼠腹主动脉内膜增生和血管重塑的影响。方法：复制球囊损伤的大鼠腹主动脉剥脱模型，12只Wistar大鼠随机分为①对照组：6只腹腔内注射intralipid（1 mL/d）；②ATRA组：6只腹腔内注射溶解于intralipid的ATRA（4 mg·kg^-1·d^-1）。球囊损伤14 d后，损伤区域的血管段用10%甲醛固定，然后染色，进行组织学观察。结果：ATRA组新生内膜面积（IA）明显小于对照组，管腔面积（LA）和外弹力膜包绕面积（EEL）则大于对照组。结论：ATRA具有抑制损伤血管的内膜增生和促进有益的血管重塑的作用。     

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.