肺炎衣原体对C57BL/6J小鼠腹膜巨噬细胞泡沫化的影响

目的:探讨肺炎衣原体在C57BL/6J小鼠腹膜巨噬细胞泡沫化过程中的作用。方法:将肺炎衣原体与C57BL/6J小鼠腹膜巨噬细胞培养72h后用油红O方法染色观察细胞的形态变化并测定细胞内胆固醇的含量。结果:肺炎衣原体能使C57BL/6J小鼠腹膜巨噬细胞胞浆内脂质颗粒增多,胆固醇酯占总胆固醇的比例增加。结论:肺炎衣原体能促进C57BL/6J小鼠腹膜巨噬细胞泡沫化。     

Piezo1在不同周龄ApoE-/-小鼠中的表达水平及对血管内皮功能的作用

目的：探明ApoE^-/-小鼠中机械敏感性离子通道Piezo1的表达变化及Piezo1在动脉粥样硬化血管内皮功能中的作用。方法：选用24只SPF级8周龄雄性ApoE^-/-小鼠为模型组，24只SPF级8周龄雄性C57BL/6J小鼠为正常对照组，高脂饲料喂饲，于高脂饲料干预的第12、14、16和18周，每组各处死6只小鼠，检测小鼠主动脉病理情况、血脂水平、血管内皮功能及Piezo1的表达。进一步选用SPF级8周龄Piezo1^flox/flox Cdh5-Cre⁺/ApoE^-/-(以下简称Cre+)小鼠与Piezo1^flox/flox Cdh5-Cre^-/ApoE^-/-(以下简称Cre-)小鼠各10只，采用高脂饲料喂养12周，从小鼠病理染色、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、内皮素1(endothelin-1,ET-1)、前列环素I₂...     

FIZZ1在ApoE基因敲除小鼠动脉粥样硬化斑块内的表达

目的:探讨FIZZ1在ApoE基因敲除小鼠粥样斑块内的表达。方法:C57BL/6JApoE基因敲除鼠及C57BL/6J野生型小鼠各9只,分别喂食高脂饲料及普通饲料,24周后处死,自主动脉根部至腹主动脉离断整支血管,石蜡包埋后作连续切片,行HE染色及FIZZ1免疫组化,检测血管斑块内FIZZ1表达情况,RT-PCR检测斑块内FIZZ1mRNA表达。结果:ApoE基因敲除鼠高脂饲养24周后,主动脉根部动脉粥样硬化明显,斑块体积较大,免疫组化及其RT-PCR可见FIZZ1及其mRNA在粥样硬化斑块内明显表达,同龄野生型C57BL/6J鼠血管壁内未见FIZZ1及其mRNA表达。结论:FIZZ1能在动脉粥样硬化斑块内表达。     

肺炎衣原体感染和高脂血症对心肌细胞NF-kappa B和AP-1的影响

目的：探讨肺炎衣原体感染和高脂血症对心肌细胞炎症的影响。 方法： 用间接免疫荧光的方法检测肺炎衣原体感染或给予高脂饮食的C57BL/6J小鼠，观察NF-κB亚单位P50和c-Fos在小鼠心肌细胞中表达程度。 结果： 肺炎衣原体感染和高脂血症能引起心肌细胞中P50和c-Fos的激活。对照组心肌细胞核中未见P50和c-Fos的表达，而3个实验组心肌细胞核中都有不同程度的P50和c-Fos表达。实验组和对照组比较P<0.01，在3个实验组间无显著差异。 结论： 在肺炎衣原体感染和高脂血症形成的早期，心肌细胞的炎症通路已被激活。     

Api6在高脂高胆固醇饮食引起肺部炎症中所发挥作用的研究*

 目的：研究凋亡抑制因子6（Api6）在高脂高胆固醇饮食所致C57BL/6J小鼠肺部炎症反应中的作用。方法：6～8周龄的C57BL/6J雄性小鼠喂养于SPF环境中,随机分成2组,分别给予普通饮食和高脂高胆固醇饮食喂养。喂养16周后收集肺组织并采用免疫组织化学和ELISA法鉴定肺组织的炎症状态。实时定量PCR和Western blotting鉴定Api6 mRNA与蛋白的表达水平,流式细胞术检测小鼠支气管肺泡灌洗液细胞凋亡情况。体外培养巨噬细胞RAW264.7,流式细胞术检测Api6对氧化型低密度脂蛋白（oxLDL）引起的细胞凋亡的影响。结果：高脂高胆固醇饮食喂养小鼠16周后,C57BL/6J小鼠肺组织出现以巨噬细胞蓄积以及肿瘤坏死因子α和单核细胞趋化蛋白1升高为主的炎症反应。与普通饮食组相比,高脂高胆固醇饮食喂养小鼠肺组织的Api6 mRNA和蛋白表达水平都显著上调（P<0.01）,同时支气管肺泡灌洗液中的巨噬细胞凋亡水平明显下降（P<0.01）。体外实验证实500 μg/L的重组Api6处理RAW264.7细胞可显著抑制oxLDL引起的细胞凋亡（P<0.05）。结论：高脂高胆固醇饮食可致C57BL/6J小鼠肺组织巨噬细胞蓄积,其机制可能与Api6抑制巨噬细胞的凋亡有关。     

奥贝胆酸对高脂喂养的C57BL/6J小鼠糖脂稳态的影响

目的 研究奥贝胆酸(OCA)对高脂喂养C57BL/6J小鼠糖脂代谢的影响。方法 给C57BL/6J小鼠喂高脂饮食(HFD)12周后，将其随机分为模型组(model)和OCA干预组(10 mg/kg,连续灌胃6周),每组10只。喂12周正常饲料的C57BL/6J小鼠作为对照组(control),模型组和对照组灌胃给予0.5%羧甲基纤维素钠(CMC-Na)。实验期间开展口服葡萄糖耐量和胰岛素耐量实验。实验结束后，测定血清中肝功能相关指标，记录肝脏质量，测定肝脏中脂质相关指标，并对肝脏进行苏木精-伊红(HE)染色；RT-qPCR检测肝脏中脂质代谢相关基因表达。结果 糖负荷和注射胰岛素后，模型组各个时间点血糖和曲线下面积(AUC)明显高于对照组(P<0.01),OCA干预组能缓解模型组小鼠糖耐量异常(P<0.05),提高胰岛素敏感性(P<0.05);模型组血清中三酰甘油(TG)、总胆固醇(TC)、游离脂肪酸(FFA)、低密度脂蛋白总胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平明显高于对照组(P<0.01),高密度脂蛋白总胆固醇(HD...     

载脂蛋白E基因敲除小鼠动脉粥样硬化早期血管外膜成纤维细胞增殖活性增强

目的:探讨动脉外膜成纤维细胞增殖与早期动脉粥样硬化病灶形成的关系。方法:选择6周龄载脂蛋白E基因敲除[apoE(-/-)]小鼠和野生型C57BL/6小鼠,高脂喂养2、4和10周后,在各个时点处死动物前24 h经腹腔注射5-溴-2-脱氧尿嘧啶(BrdU),后选取升主动脉制备连续切片,通过HE染色观察组织形态学的变化,用免疫组化方法观察不同时点血管外膜及内膜BrdU的表达变化。体外培养高脂喂养2周的apoE(-/-)小鼠和C57BL/6小鼠动脉外膜成纤维细胞,通过BrdU掺入法测定细胞增殖活性,流式细胞术测定细胞周期。结果:体内实验发现apoE(-/-)小鼠高脂喂养2周后,在无可见内膜病灶形成之前,首先在主动脉外膜发现BrdU标记的阳性细胞,之后才在损伤内膜观察到BrdU标记细胞。而C57BL/6小鼠在任何时点都未检测到BrdU标记的细胞。体外实验观察到apoE(-/-)小鼠血管外膜成纤维细胞BrdU标记的细胞数显著多于C57BL/6小鼠(P0.01),apoE(-/-)小鼠血管外膜成纤维细胞S期及G2/M期所占百分比明显高于对照组(P0.05)。结论:血管外膜成纤维细胞增殖可能参与早期动脉粥样硬化病灶形成。     

糖尿病小鼠胸主动脉环对血管收缩剂和内皮依赖性舒张剂反应的变化

目的：探讨糖尿病（DM）小鼠在不同时期离体胸主动脉环对血管收缩剂和内皮依赖性舒张剂反应的变化。 方法： 用腹腔注射链脲佐菌素（STZ）40 mg/kg诱导C57BL/6J小鼠产生糖尿病，在17、22和28周分批处死糖尿病和同年龄对照（control）组小鼠，测定其离体胸主动脉环对血管收缩剂：苯肾上腺素（PE）、60 mmol/L KCl的反应及对内皮依赖性舒张剂乙酰胆碱（ACh）的反应。 结果： DM组小鼠2周后空腹血糖≥11.1 mol/L并在整个实验过程中维持这一水平，显著高于control组，而体重显著低于control组；17、22和28周DM组胸主动脉环对PE的反应性分别高于、接近、高于control组，各时期对60 mmol/L KCl都表现高于control组；17、22和28周DM组胸主动脉环对ACh的反应性分别高于、接近、低于control组。 结论： DM组小鼠胸主动脉环对血管收缩剂的反应增强，而内皮功能先代偿性增强，然后降低，表现为内皮损伤。     

硫化氢抑制apoE基因敲除小鼠动脉粥样硬化中ICAM-1的表达

目的　探讨硫化氢(H2S)对apoE基因敲除小鼠(apoE-/-小鼠)动脉粥样硬化中细胞间黏附分子-1 (ICAM-1)的调节作用。方法　6周龄雄性C57BL/6J和apoE-/-小鼠分为C57BL/6对照组、apoE-/-组、apoE-/-+硫氢化钠(NaHS)组和apoE-/-+炔丙基甘氨酸(PPG)组,每组各8只,普通饮食饲养10周。硫电极法测定血清中H2S的含量;ELISA法测定血清中ICAM-1的含量;荧光实时定量RT-PCR法测定主动脉组织中ICAM-1 mRNA的表达。油红O染色观察小鼠主动脉根部斑块面积的变化。结果 与C57BL/6J小鼠相比,apoE-/-小鼠血清中H2S的含量明显下降(P 0.01),血清中ICAM-1的含量和主动脉组织中ICAM-1 mRNA的表达明显升高(P 0.01),主动脉根部出现明显斑块;给予NaHS后,apoE-/-小鼠血清中H2S的含量明显升高(P 0.05),血清和主动脉组织中ICAM-1的表达明显降低(P 0.01和P 0.05),动脉粥样斑块明显缩小(P 0.05);给予PPG后,apoE-/-小鼠血清中H2S的含量明显降低(P 0.05),血清和主动脉组织中ICAM-1的表达明显增高(P 0.05和P 0.01),动脉粥样斑块明显增大(P 0.01)。结论　气体信号分子H2S可明显抑制动脉粥样斑块形成过程中ICAM-1的表达与分泌。     

加味二至丸通过抑制铁死亡减轻高脂血症小鼠肝脏脂质沉积

目的:观察加味二至丸对高脂血症模型小鼠肝脏脂质沉积及铁死亡相关蛋白表达的影响.方法:30只ApoE?/?小鼠随机分为模型组、辛伐他汀组和加味二至丸组,每组10只,另取10只相同背景的C57BL/6J小鼠作为正常对照组.模型组及各治疗组均给予高脂饲料喂养,正常对照组给予普通饲料喂养.造模12周后按分组分别给予相应的药物灌...     

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 universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

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.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

'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 genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

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.