急性心肌梗死大鼠趋化因子表达与心功能的关系

目的：探讨急性心肌梗死（AMI）大鼠心肌局部趋化因子的表达与淋巴细胞浸润及心功能的关系。 方法： 结扎冠状动脉左前降支建立AMI大鼠模型，实验动物分为3组：心衰组（MI-HF）、未心衰组(MI-NF)和假手术组(sham)，假手术组只过线不结扎。于术后3 d、1周、2周检测血流动力学，将左室舒张末期压力(LVEDP)≥15 mmHg者归为心衰组。用半定量RT-PCR方法测定心肌梗死区（包括梗死周边区）趋化因子的mRNA表达，包括γ干扰素诱导的单核因子（MIG）、巨噬细胞炎性蛋白-1α（MIP-1α）、正常T细胞表达和分泌、活化时表达下降的因子（RANTES）。HE染色切片进行梗死区淋巴细胞计数分析。 结果： AMI大鼠心肌局部趋化因子的mRNA表达于术后3 d开始升高，1周达峰值，且MI-HF组较MI-NF组表达更高(RANTES, 0.83±0.05 vs 0.51±0.19, P<0.05; MIP-1α, 1.94±0.30 vs 1.48±0.33, P<0.05; MIG, 1.40±0.27 vs 0.93±0.28, P<0.05)。RANTES和MIP-1α的表达与淋巴细胞浸润显著相关(RANTES，r=0.35，P<0.05；MIP-1α，r＝0.40，P<0.05)。 结论： AMI后心肌局部趋化因子RANTES、MIP-1α、MIG表达增高，且趋化因子水平与心功能有相关性，趋化因子可能参与了AMI后心衰的病理生理学发展过程。     

雷藤舒(LLDT-8)对成纤维样滑膜细胞分泌趋化因子的影响

研究(5R)-5-羟基雷公藤内酯醇(雷藤舒,LLDT-8)对TNF-α联合IL-17诱导类风湿关节炎(rheumatoid arthritis,RA)成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)分泌趋化因子GRO-α、ENA-78、MCP-1、MIP-1α和RANTES的影响。ELISA法检测FLS上清液中GRO-α、ENA-78、MCP-1、MIP-1α和RANTES的浓度;RT-PCR法检测FLS中GRO-α、ENA-78、MCP-1、MIP-1α和RANTES mRNA的表达。结果显示LLDT-8可显著抑制TNF-α联合IL-17诱导的FLS上清液中GRO-α、ENA-78、MCP-1、MIP-1α和RANTES的表达;也可有效抑制TNF-α联合IL-17诱导的FLS GRO-α、ENA-78、MCP-1、MIP-1α和RANTES mRNA的表达。该研究提示LLDT-8通过抑制FLS产生GRO-α、ENA-78、MCP-1、MIP-1α和RANTES而在RA的治疗中发挥抗炎作用。     

急性心肌梗死大鼠心肌组织趋化因子及其受体mRNA表达的观察

目的:探讨急性心肌梗死大鼠心肌局部趋化因子和T细胞趋化因子受体的表达,揭示AMI后T细胞浸润心肌组织的机制。方法:结扎冠脉左前降支建立AMI大鼠模型,用半定量RT-PCR方法分析心肌梗死区和非梗死区趋化因子的表达,包括γ干扰素诱导的单核因子(MIG),正常T细胞表达和分泌、活化时表达下降的因子(RANTES),巨噬细胞炎性蛋白-1α(MIP-1α),以及T细胞趋化因子受体的表达(包括CXCR3、CCR3、CCR5)。HE染色切片进行心肌梗死区和非梗死区淋巴细胞计数分析。结果:心肌梗死区和非梗死区趋化因子RANTES、MIP-1α、MIG的mRNA表达于术后3天开始升高,1周达峰值,然后开始下降,8周降至正常,而趋化因子受体的表达没有明显改变。AMI大鼠心脏梗死区和非梗死区均可见淋巴细胞浸润,梗死区1周达高峰(81.0±10.3vs2.6±1.1,P<0.05),非梗死区2周达高峰(19.0±8.0vs3.2±0.8,P<0.05)。RANTES和MIP-1α的表达与淋巴细胞浸润显著相关。结论:AMI后心肌局部趋化因子表达增高,可能是诱导T细胞浸润心肌组织的始动因子。     

重组hIL-10抗家兔皮肤移植反应中CC、IL-8/CXCL8趋化因子的变化

目的:检测家兔皮肤移植经rhIL-10作用后,血清中CC、IL-8/CXCL8趋化因子的变化,探讨CC、IL-8/CXCL8趋化因子在rhIL-10抗免疫排斥机制中的作用。方法:皮肤移植家兔分6组:①rhIL-10低剂量,②rhIL-10高剂量,③CsA低剂量,④CsA高剂量,⑤rhIL-10+CsA低剂量联合和⑥生理盐水组;每只家兔均于术前1天开始肌注给药,连续注射10天;各组分别于术前1天、术后1、4、7、14、21、28天取外周血,分离血清,以ELISA法检测移植家兔血清CC、IL-8/CXCL8趋化因子水平。结果:(1)术后各组IL-8水平均升高,术后4天、7天⑥组IL-8水平高于各组(P<0.05)。(2)术后各组MCP-1水平明显升高,术后1天、4天,⑥组MCP-1水高于各组(P<0.05),术后7天⑥组MCP-1水平高于①组、⑤组(P<0.05);术后7天、14天CsA抑制组高于联合组(P<0.05)。(3)术后各组MIP-1α明显升高,术后4天⑥组MIP-1α水平高于①、③、⑤组,术后7天⑥组MIP-1α水平高于各组(P<0.05);(4)术后各组MIP-1β水平升高,但同时间段组间比较差异无统计学意义(P>0.05)。结论:CC、IL-8/CXCL8趋化因子在皮肤移植后明显升高,表明在急性排斥反应中发挥了重要作用,随排斥反应加重而进一步增高,皮片排斥后下降,可作为观察和诊断移植排斥的合适标志物。     

精神分裂症IL-1β、TNF-α和酪氨酸羟化酶的基因表达水平

目的:检测精神分裂症患者IL-1β、TNF-α和酪氨酸羟化酶(TH)的基因表达水平,探讨精神分裂症的外周神经免疫机制。方法:采用RT-PCR和半定量技术,分别检测39例精神分裂症患者、25例同胞对照和30例正常对照外周血单个核细胞IL-1β、TNF-α和TH的基因表达水平。结果:研究显示IL-1β在病例组、同胞对照组和正常对照组的基因表达水平分别为1·52±1·01、1·18±0·99和0·55±0·33;TNF-α在三组样本的基因表达水平分别为1·52±1·09、1·01±0·87和0·61±0·32;TH在三组样本的基因表达水平分别为0·74±0·38、0·70±0·29和0·28±0·20。其中病例组与同胞对照组IL-1β、TNF-α、TH基因表达水平无显著差异(P>0·05);病例组和同胞对照组的IL-1β、TNF-α、TH基因表达水平均显著高于正常对照组(P<0·05或P<0·01),且对照组IL-1β和TNF-α基因表达水平显著相关(r=0·847,P<0·01);IL-1β和TH基因表达水平显著相关(r=0·666,P<0·01)。病例组只有IL-1β和TNF-α基因表达水平表现为显著相关(r=0·942,P<0·01)。结论:精神分裂症患者可能存在致炎性细胞因子和儿茶酚胺类神经递质的过度表达,且可能受遗传背景影响。儿茶酚胺类神经递质和致炎性细胞因子的基因表达之间可能具有一种交互机制,而精神分裂症患者的这种交互机制发生了紊乱。     

趋化因子MIP-1α在干燥综合征患者唇腺组织中的表达

目的　通过研究趋化因子———巨噬细胞炎症蛋白 1α(macrophageinflammatoryprotein 1alpha ,MIP 1α)在干燥综合征 (SS)患者唇腺组织中表达的情况及其分别与唇腺淋巴细胞浸润灶数、血清γ球蛋白水平的相关性 ,探讨MIP 1α在SS发病机制中的作用及其临床意义。方法　采用逆转录 聚合酶链式反应 (RT PCR)方法检测 2 8例原发性干燥综合征 (pSS)、13例继发性干燥综合征 (sSS)和 12例对照组 (颌面部外伤和唇腺囊肿 )患者唇腺组织中MIP 1α的mRNA表达水平及其分别与唇腺淋巴细胞浸润灶数、血清γ球蛋白水平的相关性。结果　pSS组、sSS组和对照组MIP 1αmRNA的表达量分别为 0 .4 9± 0 .11、0 .4 6± 0 .12、0 .19± 0 .0 8;pSS组和sSS组MIP 1α的mRNA表达水平均较对照组明显升高 (P <0 .0 5 ) ,SS患者唇腺的MIP 1α的mRNA表达量与唇腺浸润淋巴细胞灶数 4mm2 呈正相关 (r=0 .38,P =0 .0 14 )、与血清γ球蛋白 %亦呈正相关 (r=0 .37,P =0 .0 17)。结论　MIP 1α参与了SS的发病机制 ,很可能在介导淋巴细胞从血液循环系统向唇腺组织移行的过程中起重要作用 ,并且其表达程度与SS的病情活动相关。     

T细胞受体库及细胞因子表达与胃癌进展及转移的关系

目的　了解在胃癌的发展过程中 ,肿瘤细胞与机体免疫系统间相互作用的特征。方法采用高敏感的放射性标记半定量RT PCR技术检测胃癌病人癌组织、非癌性粘膜组织及外周血各细胞亚群中细胞因子及T细胞受体亚家族mRNA的表达。结果　进展期胃癌外周血CD8+ T细胞中的增殖性T细胞克隆数低于早期胃癌 (P =0 .0 5 )。有淋巴结转移病例外周血CD8+ T细胞和CD4 + T细胞中的增殖性T细胞克隆数较无转移组明显减少 (P =0 .0 0 0 17、P =0 .0 16 )。有淋巴结转移病例的癌组织 ,其CD8+ T细胞中IL 6、IL 8、TNF α和CD4 + T细胞中IL 4mRNA的水平 (0 .4 3± 0 .17、0 .4 2± 0 .11、0 .18± 0 .0 5、0 .0 8± 0 .0 3)均较非癌性粘膜组织中的 (0 .0 8± 0 .0 2、0 .17± 0 .0 5、0 .0 8± 0 .0 3、0 .0 1± 0 .0 0 )增高 (P =0 .0 4 0、P =0 .0 2 0、P =0 .0 17、P =0 .0 34) ;而无淋巴结转移病例的癌组织与非癌性粘膜组织中各细胞因子的表达均未发现统计学差异。结论　胃癌病人T细胞受体库及细胞因子表达与胃癌进展及转移相关 ,进展期胃癌及发生转移的病例免疫系统受到抑制。     

抑郁症患者血清细胞因子、C-反应蛋白和锌水平的变化及其临床意义

目的:探讨IL-6、IL-1β、TNF-α、CRP、Zn在抑郁症病理生理机制中的作用。方法:抑郁症患者33例,正常对照组23例。采用酶联免疫吸附法(ELISA)测定抑郁症患者和正常对照组的血清IL-6、IL-1β、TNF-α的水平,同时采用散射比浊法测定血清CRP,化学比色法测定血清Zn水平。于治疗前评定汉密尔顿抑郁量表(HAMD)。结果:①抑郁症血清IL-6[(8.90±5.63)pg/ml]、TNF-α[(13.57±7.63)pg/ml]、CRP[(6.18±5.68)mg/L]水平显著高于正常对照组(IL-6:5.95±3.66;TNF-α:12.87±5.34;CRP:2.50±1.44),且血清Zn水平[(11.88±2.37)μmol/L]显著低于正常对照组(13.60±1.90);抑郁症组血清Zn水平女性患者(11.19±2.21)显著低于男性患者(14.04±1.48)。②抑郁症血清IL-6水平与TNF-α有显著的正相关(r=0.470,P<0.01),而血清IL-1β水平与Zn有显著的正相关(r=0.346,P<0.05)。③抑郁症血清Zn与HAMD中迟缓因子分有显著的正相关(r=0.351,P<0.05),与性别有明显的正相关(r=0.576,P<0.01)。结论:①在抑郁症组血清IL-6、TNF-α、CRP水平升高可能是抑郁症的免疫学标志之一;②抑郁症中细胞因子IL-1β表达异常与微量元素锌密切相关,提示可能与抑郁症发病机制有关。     

硫辛酸抑制脂多糖诱导的星形胶质细胞细胞因子及趋化因子的表达

目的探讨硫辛酸(LA)对脂多糖(LPS)激活的星形胶质细胞分泌TNF-α、IL-1β、IL-6和IL-10及相关趋化因子的影响。方法分离并鉴定新生C57BL/6小鼠大脑皮质星形胶质细胞,1μg/mL LPS刺激第2代星形胶质细胞,100μg/mL LA进行干预,Griess法检测NO的分泌,ELISA检测TNF-α、IL-1β、IL-6和IL-10炎性因子的含量,反转录PCR检测炎症趋化因子CC亚族趋化因子配体20(CCL20),单核细胞趋化蛋白1(MCP-1)和巨噬细胞炎性蛋白1α(MIP-1α)mRNA的表达。结果与正常组比较,LPS刺激星形胶质细胞后,NO、TNF-α、IL-1β、IL-6分泌显著升高,IL-10分泌下调(P0.05);LA能抑制LPS诱导的NO、TNF-α、IL-1β、IL-6的分泌,增加IL-10的分泌,与LPS组相比差异有统计学意义(P0.05)。LA能显著下调LPS所致的CCL20、MIP-1α、MCP-1 mRNA的分泌。结论 LA能抑制LPS激活星形胶质细胞所致的炎性反应,其作用与抑制炎性因子及趋化因子的分泌有关。     

老年急性冠状动脉综合征患者CRP与TNF-α、IL-1β相关性研究

目的 :观察老年冠心病不同类型患者中肿瘤坏死因子α(TNF -α)、白细胞介素 1β(IL - 1β)水平变化及其与C反应蛋白 (CRP)之间的关系 ,进一步探讨急性冠状动脉综合征临床识别和预测的炎症指标。方法 :采用放射免疫分析测定血清TNF -α、IL - 1β和CRP的浓度。 结果 :急性冠脉综合征患者 (ACS)TNF -α和IL- 1β水平均显著高于对照组 (p <0 0 5 ;p <0 0 1)和稳定性冠心病患者 (p <0 0 5 ;p <0 0 1)。ACS患者CRP水平(7 99± 11 9)mg L显著高于SCHD组 (2 71± 5 4 5 )mg L ,p <0 0 5和对照组 (0 99± 1 5 )mg L ,p <0 0 1。CRP水平与TNF -α呈显著正相关 (r=0 5 4 5 ,p <0 0 1) ;与IL - 1β亦呈明显正相关 (r=0 31,p <0 0 5 )。 结论 :老年冠心病患者细胞因子表达异常与炎性标志物CRP密切相关 ,提示可能与急性冠脉综合征的发生有关 ,是动脉粥样硬化斑块不稳定的标志     

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.     

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 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.