高血压病患者血浆同型半胱氨酸测定的临床意义

目的分析血浆同型半胱氨酸(tHCY)浓度对高血压病患者发生靶器官损害的影响。方法采用荧光偏振免疫法检测84例高血压病患者及96例健康体检者tHCY、叶酸、维生素B12(VB12)并对其相关性进行分析。结果(1)高血压组tHCY水平(22.18±12.34μmol/L)明显高于对照组(14.94±6.98μmol/L,P＜0.05)。高血压组叶酸(4.80±1.76ng/m1),VB12水平(237.0±31.11pg/ml)显著低于对照组(5.58±2.56ng/ml,257.45±60.67pg/ml.P＜0.05)。(2)高血压组中,高tHCY血症组约71.43％合并心脑肾等靶器官损伤,明显高于正常tHCY组42.86％(P＜0.05)。(3)高血压组中血浆tHCY浓度与叶酸、VB12呈负相关(r=-0.6090.r=-0.5577.P＜0.05)。结论高血压病患者中tHCY水平较高,可能是较易发生心、脑、肾等靶器官损害的一个重要因素。并且体内叶酸、VB12水平与HCY呈现负相关提示高血压患者补充叶酸、VB12可能会延缓其靶器官的损害。     

冠心病患者血清同型半胱氨酸水平与冠状动脉病变程度的关系

目的:研究血清同型半胱氨酸(Hcy)含量与冠状动脉病变程度的关系。方法:选择我院心内科2008年10月～2009年10月住院并行冠状动脉造影的病例325例,根据冠状动脉造影结果分为冠心病组(CHD组,284例)和非冠心病组(非CHD组,41例)。比较两组Hcy、叶酸(FA)、维生素B12(VB12)及血脂水平的差异,并分析CHD组中不同程度冠脉病变(单支、双支、多支病变)患者Hcy水平变化,以及CHD危险因素的Logistic回归分析。结果:(1)CHD组患者Hcy水平(24.36±6.62μmol/L)明显高于非CHD组(12.26±4.10μmol/L),且与总胆固醇(TC)、甘油三酯(TG)成正相关,与高密度脂蛋白(HDL)、FA、VB12成负相关。(2)单支、双支、多支冠脉病变CHD患者的Hcy水平随冠脉病变支数的增加而升高,且高于非CHD组。(3)Logistic回归分析显示,高Hcy、TC、TG,低FA、HDL、VB12为CHD的危险因素。结论:血清Hcy水平是反映CHD严重程度的重要指标。     

血清同型半胱氨酸及叶酸、维生素B12与脑血管病的关系

为了探讨血清同型半胱氨酸(homocysteine,Hcy)、叶酸、维生素B12水平与脑血管疾病发病及其并发症之间的关系,采用荧光偏振免疫分析法和化学发光法分析比较了148例脑血管病患者和32名对照组血清Hcy、叶酸、维生素B12水平.结果显示:血清Hcy含量在脑梗死组、脑出血组及椎-基底动脉供血不足组中均明显高于对照组(P＜0.001,P＜0.001,P＜0.01);叶酸和维生素B12的浓度明显低于对照组(P＜0.05);存在高血压、糖尿病、冠心病等并发症患者血清Hcy、叶酸、维生素B12水平与无并发症患者间无显著差异(P＞0.05);脑血管病患者中血清Hcy水平升高与否在不同并发症及无并发症患者间无显著性差异(P＞0.05).表明高Hcy血症是脑血管病发病的独立危险因素之一,与叶酸和维生素B12水平下降有关,与高血压、糖尿病和冠心病等并发症无明显关联.     

血浆同型半胱氨酸水平与血管性痴呆的关系

目的:探讨血浆同型半胱氨酸(Hcy)、血清叶酸和维生素B12水平与血管性痴呆(VD)的关系.方法:应用反相高效液相色谱法(RP-HPLC)测定30例VD患者的血浆Hcy水平,用放射免疫法(RIA)测定其血清叶酸及维生素B12水平,并与58例非痴呆脑梗死患者和30例同龄对照比较.结果:VD组血浆Hcy水平显著高于非痴呆脑梗死组:非痴呆脑梗死组血浆Hcy水平显著高于同龄对照组;VD组血清叶酸水平明显低于非痴呆脑梗死组;非痴呆脑梗死组血清叶酸水平明显低于同龄对照组.结论:Hcy可能是VD发病的一个危险因素.     

同型半胱氨酸、叶酸、维生素B12与阿尔茨海默病精神行为症状的相关性

目的:探讨阿尔茨海默病(AD)患者的精神行为症状(BPSD)与同型半胱氨酸(Hcy)、叶酸、维生素B12的相关性。方法:选取40例伴有BPSD的AD患者和39例不伴BPSD的AD患者,以及39名正常对照者。分别测定所有被试的Hcy、叶酸及维生素B12水平并进行临床评估和认知评估。结果:3组研究对象血浆Hcy、叶酸、维生素B12水平存在差异,且差异有统计学意义(F=14.76,57.53,88.84;P0.01)。两AD组患者血浆Hcy水平较正常对照组高,叶酸、VitB12水平较正常对照组低,差异有统计学意义(t=2.53,5.36,-8.68,-10.91,-13.39,-8.54;P0.01),BPSD组较非BPSD组Hcy水平高,而VitB12水平低,差异有统计学意义(t=2.92,-4.28;P0.01)。在两个患者组中,认知功能与Hcy水平呈负相关(r=-0.602;P0.05),与维生素B12水平呈正相关(r=0.225;P0.05)。结论:Hcy、叶酸、维生素B12水平与AD相关,Hcy、维生素B12可能参与了AD患者BPSD的发病机制。     

血清叶酸及同型半胱氨酸与出生缺陷的关系

目的 探讨血清叶酸及同型半胱氨酸水平与出生缺陷发生的关系及在产前诊断中的价值.方法 选择孕中期产前筛查高风险且产前诊断胎儿有先天性异常的孕妇19例为A组,孕中期产前筛查高风险,但产前诊断胎儿正常的孕妇60例为B组,孕中期产前筛查低风险,经B超检查(部分经彩超检查)未见胎儿有CHD、NTD、CL且产后新生儿检查未见上述畸形的孕妇26例为C组,采用免疫荧光时间分辨法测定血清FA,化学发光法测定血清Hcy.结果 1.A组血清FA平均值为18.90±5.65 nmol/L, B组血清FA平均值为25.40±8.06 nmol/L,C组血清FA平均值为36.46±11.27 nmol/L,三组血清FA水平两两比较,差异有统计学意义(P＜0.01).2.A组血清Hcy平均值为19.62±6.01μmol/L,B组血清Hcy平均值为15.78±2.29μmol/L,C组血清Hcy平均值为13.05±2.10μmol/L,三组间两两比较,差异有统计学意义(P＜0.001).3.统计学分析显示,三组血清FA与Hcy均存在明显负相关(P＜0.05).结论 1.母体内血清FA水平低下、Hcy升高对出生缺陷有着重要的影响;2.FA与Hcy存在明显负相关,提示血清FA异常对Hcy有重要影响;3.母体血清FA浓度<21.55 nmol/L和/或Hcy浓度>19.90 μmol/L有可能作为产前筛查高风险孕的妇产前诊断的新指征.     

同型半胱氨酸对外周血内皮祖细胞数量和功能的影响

目的：观察同型半胱氨酸(Hcy)对外周血内皮祖细胞(EPCs)的影响。方法： 密度梯度离心法获取外周血单个核细胞，将其接种在人纤维连接蛋白包被的培养板，培养7 d后，收集贴壁细胞，加入不同浓度Hcy(10 μmol/L、50 μmol/L、100 μmol/L和200 μmol/L)干预一定时间(6 h、12 h、24 h和48 h)。多波长激光共聚焦显微镜鉴定FITC-UEA-Ⅰ和DiI-acLDL双染色阳性细胞为正在分化的EPCs，流式细胞仪检测其表面标志进一步鉴定EPCs，倒置荧光显微镜下计数。采用MTT比色法、改良的Boyden小室、粘附能力测定实验和体外血管生成试剂盒分别观察EPCs的增殖能力、迁移能力、粘附能力和体外血管生成能力。结果：Hcy呈量效和时效地减少EPCs数量，200 μmol/L Hcy作用24 h后EPCs数量明显少于对照组(35.7±6.7 vs 62.5±10.6，P＜0.01)，并损害EPCs增殖(0.531±0.061 vs 0.328±0.055，P＜0.01)、迁移(26.3±6.4 vs 6.4±3.7，P＜0.01)、贴壁(33.1±8.1 vs 17.4±7.5，P＜0.01)、和体外血管生成(25.4±9.1 vs 10.4±4.7，P＜0.01)。 结论： Hcy不但减少EPCs数量并损害其功能。     

老年性痴呆患者血浆同型半胱氨酸、镁离子水平变化及与年龄的相关性分析

目的:检测分析两类老年性痴呆患者血浆同型半胱氨酸(Hcy)和镁离子(Mg2+)水平变化及与年龄的关系。方法:老年性痴呆患者共99例,其中阿尔茨海默病46例(AD组)、血管性痴呆53例(VD组)、另选65例健康人群作对照组。以循环酶法测定各组血浆Hcy水平,以亚甲蓝显色法测定各组血浆Mg2+水平,并进行组间比较和相关性分析。结果:血浆Hcy浓度,与对照组(11.91±3.77μmol/L)比较,AD组(17.69±3.93μmol/L)和VD组(19.91±4.23μmol/L)均明显升高(P<0.01);血浆Mg2+浓度,与对照组(1.03±0.15mmol/L)比较,AD组(0.69±0.17mmol/L)和VD组(0.71±0.17mmol/L)均明显降低(P<0.01);AD组、VD组血浆Hcy浓度均随着年龄的增长而升高,相关系数r分别为0.551、0.479(P均<0.05)。结论:针对高危人群定期测定血浆Hcy、Mg2+水平,对AD和VD的诊断与预后有积极意义。     

叶酸和维生素B_(12)在同型半胱氨酸诱导人脐静脉内皮细胞凋亡中的作用

目的:探讨叶酸和维生素B_(12)在同型半胱氨酸(Hcy)通过哺乳动物不育系20样激酶1(MST1)诱导人脐静脉内皮细胞(HUVECs)凋亡中的作用及机制。方法:将HUVECs分为3组,分别为对照组(0μmol/L Hcy)、Hcy组(100μmol/L Hcy)和干预组(100μmol/L Hcy+30μmol/L叶酸+30μmol/L维生素B_(12))。细胞处理72 h后,流式细胞术检测HUVECs的凋亡率;荧光倒置显微镜观察DNA甲基转移酶1(DNMT1)过表达腺病毒转染的效率;RT-qPCR和Western blot分别检测MST1及DNMT1的mRNA和蛋白表达水平;巢式甲基化特异性PCR法检测MST1启动子区的甲基化水平。结果:与正常对照组比较,Hcy组HUVECs的凋亡率升高(P0.01),MST1的mRNA(P0.01)与蛋白(P0.05)表达水平明显增加,DNMT1的mRNA水平降低(P0.01);而叶酸和维生素B_(12)干预可明显抑制Hcy引起的HUVECs凋亡、MST1 mRNA水平升高(P0.01)及DNMT1 mRNA水平降低(P0.01),MST1的mRNA水平与HUVECs凋亡率呈正相关(r=0.943 9,P0.001)。转染DNMT1过表达腺病毒后,可见HUVECs中大量绿色荧光蛋白表达;同时,DNMT1的mRNA和蛋白表达(P0.01)以及MST1启动子区的DNA甲基化水平明显增加(P0.01),而MST1的蛋白水平下降(P0.01)。结论:MST1表达增加可以诱导HUVECs凋亡,而叶酸和维生素B_(12)在缓解Hcy介导的HUVECs凋亡中发挥重要作用,其保护机制可能是通过上调MST1启动子区DNA甲基化实现的。这将为进一步研究动脉粥样硬化的发病机制提供理论依据。     

甲基维生素B12对大鼠自身免疫性脑脊髓炎的治疗及溶血磷脂酸水平的影响

研究实验性自身免疫性脑脊髓炎 (EAE)及甲基维生素B12治疗中溶血磷脂酸 (LPA)水平的变化。通过注射豚鼠脊髓匀浆和完全弗氏佐剂诱导大鼠发生EAE。用有机溶剂提取、并进一步分离 ,最终用定磷方法测定甲基维生素B12治疗的EAE大鼠血浆及脑溶血磷脂水平 ,未经治疗的EAE大鼠为对照组。发现甲基维生素B12治疗组EAE大鼠与未经治疗EAE大鼠比较 ,恢复期脑与血浆LPA水平增高 ,分别为 30 2 3± 11 5 9μmol L血浆、2 45 4 5±144 89nmol g脑和 9 2 7± 3 2 5 μmol L血浆、5 6 33± 5 6 6nmol g脑 (P <0 0 5 ) ;急性期血浆的LPA增高 ,分别为 10 0 5± 1 70 μmol L血浆和 1 87± 0 5 9μmol L血浆 (P <0 0 5 )。溶血磷脂酸可能参与自身免疫性脑脊髓炎髓鞘的恢复过程。     

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.