CD133+胶质瘤干细胞在胶质瘤中的分布

恶性胶质瘤是人类最致命的肿瘤之一,因其血管丰富和弥漫浸润性生长,使得手术不能全部切除并极易复发,患者预后差.因胶质瘤干细胞(GSCs)是胶质瘤发生、发展的源头,因而越来越多的受到关注.干细胞标志物CD133广泛表达于人体多种肿瘤中,同时,它也足研究得最多且应用最广泛的胶质瘤干细胞表面标志物.了解CD133+胶质瘤干细胞在胶质瘤中的分布可为临床靶向治疗恶性胶质瘤提供依据.     

长链非编码RNA CRNDE基因不同转录本在胶质瘤组织中的表达差异分析

目的 探讨长链非编码RNA CRNDE不同转录本在不同级别胶质瘤中的表达情况.方法 利用Real-time PCR方法,检测10种CRNDE转录本(a-j)在非肿瘤脑组织、低恶性程度胶质瘤组织、高恶性程度胶质瘤组织中的表达变化.结果 CRNDE 10个转录本在胶质瘤组织中表达均明显升高.低恶性程度组织中各个转录本之间变化差异不大,变化倍数为非肿瘤组织的3～7倍.高恶性程度胶质瘤组织中,各转录本之间变化差异明显,其中转录本g表达变化最大,为非肿瘤组织的195倍,转录本a、b、c、d、e、i、j表达水平较非肿瘤组织升高50～ 100倍,转录本f、h表达水平较非肿瘤组织升高25～50倍.转录本g△Ct值的ROC曲线表明区别正常样本、低恶性程度和高恶性程度胶质瘤的阈值为12.40和9.29.结论 与低恶性程度组织相比,高恶性程度胶质瘤组织中CRNDE各个转录本之间变化差异明显,其中转录本g表达变化最大,具有作为胶质瘤检测标志物的可能性.     

免疫治疗在脑胶质瘤中的研究进展

脑胶质瘤是神经系统最常见的恶性颅内肿瘤.传统的治疗方式虽然能有效的抑制脑胶质瘤的生长,但是由于其高恶性程度和高复发率,恶性胶质瘤患者的术后生存期没有显著改善.研究证实,免疫治疗不仅发挥肿瘤杀伤作用,还能提升宿主的抗肿瘤免疫反应应答,被认为是难治性肿瘤的重要的辅助治疗策略.     

多模态MRI影像组学在脑胶质瘤中的应用进展

影像组学在肿瘤的诊断、预后评估, 以及评价肿瘤对治疗的反应等方面均发挥着关键作用。多模态磁共振成像(MRI)影像组学可以将肿瘤的影像组学表现与其分子表型联系起来, 在脑胶质瘤的分级和治疗反应的预测和预后方面具有更大的优势。它利用常规和先进技术将脑肿瘤与非肿瘤性病变进行区分, 可用于脑胶质瘤的诊断和脑胶质瘤与脑转移瘤的鉴别;半自动和自动化的肿瘤分割技术也被开发用于评估脑胶质瘤的复发情况。主要对多模态MRI影像组学在预测胶质瘤重要分子生物学标志物、胶质瘤分级诊断、与脑转移瘤的鉴别诊断及评估术后复发方面的研究进展进行综述。     

增强恶性胶质瘤树突状细胞疫苗疗效的策略

恶性胶质瘤是最常见的颅内恶性肿瘤.近年来,树突状细胞(DC)疫苗在治疗恶性胶质瘤方面取得了一定进展.研究证实,DC疫苗能延长恶性胶质瘤患者的生存期.负载胶质瘤抗原的DC疫苗有效克服胶质瘤细胞引起的免疫抑制,激活机体免疫系统清除胶质瘤的同时对正常细胞不造成伤害,故其在恶性胶质瘤治疗上有良好的应用前景.高特异性抗原的选择、对肿瘤微环境中调节性因子及DC表面分子的调节等多种免疫策略的采用可有效提高DC疫苗激活机体免疫系统的能力.     

人脑胶质瘤组织中骨形成蛋白-2的表达及其临床病理学意义

目的:探讨骨形成蛋白-2(BMP-2)在人脑胶质瘤中的表达和临床意义.方法:随机选取脑胶质瘤患者88例, 采用SABC免疫组化方法和RT-PCR技术, 检测脑胶质瘤组织和正常脑组织中BMP-2蛋白及其mRNA的表达.并分析其与脑胶质瘤组织临床分级之间的关系.结果:BMP-2蛋白在脑胶质瘤组织中的阳性表达率为78.40% (69/88), 明显高于(P<0.01)其在正常脑组织中的阳性表达率[3% (6/20)].BMP-2蛋白与mRNA 在脑胶质瘤高级别组(Ⅲ～Ⅳ级) 中的表达均明显高于低级别组(Ⅰ～Ⅱ级), 说明随着肿瘤级别的升高BMP-2表达也增强.结论:BMP-2蛋白及其mRNA的异常表达可能与脑胶质瘤的恶性程度有关, 可以作为一个肿瘤标志物在临床中应用.     

肿瘤标志物检测技术研究进展

肿瘤标志物的联合检测为肿瘤的筛查和早期诊断带来了新的发展机遇.寻找具有较高灵敏度和特异性的肿瘤标志物一直是肿瘤研究领域的热点之一.随着分子生物学、免疫学诊断技术的飞速发展,通过多种检测技术的联合应用,互相补充,以实现对肿瘤的早期诊断和治疗.     

胶质瘤生物学标志的研究进展及其应用前景

胶质瘤是最常见的颅内原发性肿瘤,占原发性脑肿瘤的60%～70%.因多数呈漫润性生长,手术不易全切,复发率高,预后普遍较差,恶性胶质瘤的中位生存期仅13个月.寻求有效治疗手段,改进治疗策略,实施有针对性的个体化治疗,是改善胶质瘤治疗效果和患者预后的必由之路,同时也对病理诊断在指导临床治疗方面的作用提出了更高的要求.     

脑胶质瘤组织中内皮抑素的表达及其与血管形成的关系

目的:探讨内皮抑素在脑胶质瘤组织中的表达和意义及其与血管形成的关系.方法:免疫组化方法检测46例脑胶质瘤组织及5例正常脑组织中内皮抑素的表达水平及CD34标记的微血管密度.结果:内皮抑素在脑胶质瘤组织中高表达,并随着肿瘤恶性程度的增高而增强,且内皮抑素表达强度与肿瘤组织中微血管密度呈正相关.结论:内皮抑素在胶质瘤的发生、发展中起重要作用;且可能成为判断胶质瘤的恶性程度及预后的有效指标.     

胚胎干细胞关键因子Nanog在胶质瘤中的表达及意义

目的 探讨胚胎干细胞关键因子Nanog在人胶质瘤中的表达及意义。方法 通过免疫荧光双标技术,分析40例胶质瘤组织内胚胎干细胞关键因子Nanog与肿瘤干细胞相关基因Nestin、CD133及胚胎干细胞全能性相关基因Oct4 的共表达情况,并通过RT-PCR、Western blotting技术分析胶质瘤组织内Nanog与脑胶质瘤恶性程度之间的关系。结果 Nanog在胶质瘤组织中的表达随着胶质瘤病理级别增高而升高,而且超过50%的Nanog阳性细胞同时表达Nestin和CD133。95%以上的Nanog阳性细胞都同时表达胚胎干细胞全能性相关基因Oct4。结论 胶质瘤组织中Nanog多表达在肿瘤干细胞中,与胶质瘤的恶性程度呈正相关,在胶质瘤的发生、发展过程中起着重要作用,为研究胶质瘤的起源及胶质瘤的诊断和预后判断提供帮助。     

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.