极低频电磁暴露对钙离子跨膜迁移的影响及机理分析

目的:研究极低频（ELF）电磁暴露对细胞钙离子跨膜迁移的影响。 方法:以人体肝癌细胞为对象,激光扫描共聚焦显微镜为检测手段,研究细胞钙离子跨膜迁移对ELF电磁暴露的响应。 结果:在磁场强度为1.78×10-7 T条件下,与对照组对比,各暴露组均对不同频率和电场强度组合的外加电磁暴露环境有响应,其中[f=16 Hz]且[EP=53 Vm]、[f=45 Hz]且[EP=53 Vm]以及[f=16 Hz]且[EP=80 Vm]的电磁暴露可使钙离子跨膜迁移量显著上升,而[f=32 Hz]且[EP=53 Vm]、[f=60 Hz]且[EP=53 Vm]、[f=16 Hz]且[EP=26 Vm]以及[f=16 Hz]且[EP=87 Vm]的电磁暴露未使钙离子跨膜迁移量显著上升。 结论:不同频率和电场强度组合的ELF电磁暴露均会引起钙离子跨膜迁移量产生变化且呈现出明显差异,这可为ELF电磁环境下生物学应用提供实验依据;注重细胞膜离子通道物理、生物特性基础上探讨ELF电磁暴露对钙离子跨膜迁移影响的机理。     

电磁波的生物学窗效应

本文分别以人的肝癌细胞和动物脑组织为生物学对象，以荧光标记和同位素示踪为实验方法，以激光扫描共聚焦显微镜和液体闪烁计数器为检测仪器，以荧光强度和放射性强度为检测Ca^2 量的特征指标，进行了电磁波生物学非热效应的典型代表--电磁波生物学窗效应的实验研究。两种实验均表明了电磁波生物学频率窗效应和强度窗效应的存在且有相同的窗频率。基于本文的实验研究并结合其他文献的结果，可发现电磁波生物学窗效应具有以下基本特征：(1)不同生物组织都会在15—16Hz左右存在一个频率窗；(2)生物学窗效应既可由ELF(极低频)正弦(调制波)振幅调制的高频电磁波(载波)产生，又可由ELF连续波或ELF脉冲波产生，只是前者的频率窗只体现在调制波频率上而不体现在载波频率上，而且，前者的窗效应频率与后者的窗效应频率是相同的；(3)频率窗分布的一般规律为fn＝(2n 1)fc，式中，n＝0，1，2…，fn为第n个窗频率，fc为基频即最低的那个窗频率。实验研究还表明，这-分布规律在0—135Hz范围内是正确的，且基频fc≈15—16Hz；(4)只有特定频率参数与特定强度参数恰当组合的电磁波才能产生生物学窗效应，或者说，窗效应是电磁波频率和强度的二元函数。     

细胞胞浆Ca2+浓度的时-频分析及ELF脉冲电磁波产生的生物学窗效应

本研究以实验为基础，对细胞胞浆Ca^2＋浓度进行时-频分析，进而研究ELF脉冲电磁波在细胞胞浆Ca^2＋浓度时-频域内产生的生物学效应和生物学窗效应。结果表明：细胞胞浆Ca^2＋浓度在时-频域内有其固有的频谱特征，其中包括连续谱和离散谱。有的参数的电磁波可在细胞胞浆Ca^2＋浓度的时-频域内产生生物学效应而有的参数的电磁波却不能。若能够产生生物学效应，则有两个特征：一是使胞浆Ca^2＋浓度在时-频域内的连续谱变窄，具体表现为连续谱中的高能谱分量被抑制；二是使离散谱的分布和离散谱的频率发生了变化。同时，能够在细胞胞浆Ca^2＋浓度的时-频域内产生生物学效应的电磁波脉冲频率和脉冲强度是离散的和间隔的，这意味着，ELF脉冲电磁波能够在细胞胞浆Ca^2＋浓度的时-频域内产生生物学窗效应。本研究使用的脉冲频率范围内有两个频率窗，它们是16Hz和45Hz；使用的脉冲强度范围内有一个强度窗，是53V／m。     

离子跨膜迁移的几率波理论

基于细胞结构、已有的机理分析理论和实验事实,我们提出解释电磁场生物学窗效应的几率波理论。该理论将细胞膜通道看成是周期性分布的势垒,给出了离子跨膜迁移的物理图像;修正了膜通道内离子能量相对于外加电磁场频率的关系;应用波函数的概念,给出了低强度电磁场作用下,离子跨膜迁移的几率。数值仿真结果分析了影响离子跨膜迁移的物理因素。结果显示该理论可解释电磁场生物学窗效应的现象。     

不同频率脉冲电磁场对人卵巢癌SKOV3细胞增殖、凋亡及迁移的影响

研究不同频率的脉冲电磁场(PEMF)对人卵巢癌SKOV3细胞增殖、凋亡和迁移的影响,为PEMF治疗或预防卵巢癌切除术后发生骨质疏松患者的安全性提供实验参考数据。分别对体外培养的人SKOV3细胞施加不同频率(8、16、32和64Hz)、固定强度为1mT的PEMF,2次/d,30min/次,间隔12h,共3d,以未施加PEMF的细胞作为对照组。分别采用EdU荧光法、Annexin V-FITC荧光法和划痕实验检测SKOV3细胞增殖、凋亡及迁移的情况。结果:频率8Hz的PEMF能明显抑制SKOV3细胞的增殖,并诱导其凋亡。频率8Hz和32Hz的PEMF能明显促进人卵巢癌细胞SKOV3的迁移,而频率16Hz的PEMF却明显地抑制SKOV3细胞的迁移。提示不同频率的PEMF对人卵巢癌细胞SKOV3增殖、凋亡及迁移的影响不同。在临床中对于卵巢癌切除术后的骨质疏松患者,应当慎重考虑PEMF治疗的安全性,并严格选择治疗参数。     

极低频磁场对胞内钙振荡影响的机理分析

基于双钙库模型,本文以离子跨过细胞膜、细胞器膜迁移的几率作为细胞对电磁场的响应因子,来调制流过膜通道的离子的速率,进而影响细胞内钙离子的浓度。数值分析表明:在极低频磁场的作用下,一定能量因子下的频率条件或是一定频率因子下的能量条件可引起钙振荡形式的变化;窗效应是频率因子和能量因子共同作用的结果。     

135Hz极低频电磁场对HepG-2细胞内Ca^2＋浓度的影响

目的:研究135 Hz(电场强度为80 V·m-1)极低频电磁场(ELF)暴露对HepG-2细胞内Ca2+浓度的影响.方法:采用荧光探针Fluo-3/AM标记细胞内Ca2+,135 Hz ELF照射HepG-2细胞1 h后,利用激光扫描共聚焦显微镜技术测定细胞内Ca2+浓度,加入L-型Ca2+通道拮抗剂硝苯地平,探讨135 Hz ELF影响HepG-2细胞内Ca2+浓度变化的具体机制.结果:未暴露组细胞荧光强度较弱,ELF暴露组细胞荧光强度增高,与未暴露组有统计学意义(P<0.01);用硝苯地平干预组细胞荧光强度减弱,与未干预组有统计学意义(P<0.01).结论:135 Hz ELF可能通过引起L-型Ca2+通道的开放造成HepG-2细胞发生Ca2+超载.     

不同电刺激信号对大鼠雪旺细胞增殖的影响

目的研究不同的电刺激信号对大鼠雪旺细胞(RSC96)增殖的影响。方法实验使用RSC96细胞系(中国科学院典型培养物保藏委员会细胞库),经过2次传代培养,以1.25×10~4/孔的密度种植于24孔细胞培养板中,次日电刺激信号分别采用不同的电压(10、100、500、1 000、5 000、10 000 m V/cm)、不同的频率(0.1、1.0、100.0、1 000.0、10 000.0、1 000 000.0 Hz)、不同的脉冲占空比(5%、10%、30%、50%、70%、90%)及不同的波形(正脉冲波、矩形波、三角波、正弦波、杂波、直流波)对细胞进行电刺激,每组设置3个平行样,细胞每天刺激30 min,持续刺激4 d。采用四甲基偶氮唑盐(MTT)法检测细胞增殖率。结果当电刺激频率为100.0 Hz、脉冲占空比为50%、波形为矩形波时,电压500 m V/cm时对细胞的增殖具有抑制作用。当电刺激频率为100.0 Hz、脉冲占空比为50%、电压为500 m V/cm时,正脉冲波、正弦波、矩形波和三角波都能够促进细胞的增殖。当电刺激波形为矩形波、脉冲占空比为50%、电压为500 m V/cm时,频率100.0~1 000.0 Hz组细胞增殖率最高。当电刺激波形为矩形波、频率为100.0 Hz、电压为500 m V/cm时,不同的脉冲占空比对细胞增殖的影响不明显。结论不同的电刺激信号条件对细胞增殖的影响较大。电压≤500 m V/cm、有规律的脉冲波形、频率为100.0~1 000.0 Hz电刺激信号能够获得较好的RSC96增殖的效果。实验所获得的优化电刺激参数在外周神经修复中具有非常大的应用前景。     

极低频三角形电磁场对成骨细胞的影响

目的:观察三角形极低频电磁场对新生大鼠颅盖骨成骨细胞增殖与分化的影响.方法:采用频率为15Hz、不同强度、不同形状的三角形电磁场作用于成骨细胞,测量成骨细胞的增殖与碱性磷酸酶活性(ALP).结果:频率为15 Hz, 强度为4 mT～5 mT,三角形电磁场能够显著提高成骨细胞的增殖率和ALP的活性,而强度为8 mT时则显著抑制成骨细胞的增殖与ALP的活性;不同形状的三角形电磁场也明显影响成骨细胞的功能,其中以p为38%、85%对成骨细胞的影响最为明显.结论:电磁场的生物学效应依赖于其参数特征.     

脉冲电磁场防治骨质疏松的动物实验装置研制及实验观察

目的根据脉冲电磁场治疗骨质疏松的原理，设计用于动物实验的脉冲电磁场治疗装置．并用该装置观察在脉冲电磁场作用下实验动物力学特性和骨组织形态的变化。方法设计了强度为11MT．频率12Hz／8Hz自动跳变的脉冲电磁场发生装置和专用的动物实验装置，并将磁场作用于去势大鼠的骨质疏松模型。结果实验装置运行时．对各参数检测表明，实验装置满足设计的要求：经脉冲电磁场装置治疗的大鼠骨形态和力学特性与未经治疗的模型组都有明显改善。结论实验装置满足设计要求，脉冲电磁场可以改善骨的形态和骨骼的力学特性。     

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.