非小细胞肺癌中S100A2、S100A4及S100P表达及意义

目的研究钙结合蛋白S100家族中S100A2、S100A4及S100P基因在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达,阐明其与肺癌发生及转移的关系。方法以12例正常肺组织为对照,采用半定量RT-PCR技术检测17例腺癌和12例鳞癌及其癌旁组织中S100A2、S100A4及S100P mRNA的表达水平。结果(1)S100A2、S100A4及S100P mRNA在NSCLC中的表达量均高于癌旁和正常组织。(2)肺腺癌中三者mRNA表达量均高于癌旁和正常组织;肺鳞癌中S100A4和S100P mRNA的表达量高于正常组织。(3)根据不同的临床分期,S100A2、S100A4 mRNA在Ⅱ期与Ⅲ期中的表达量均高于Ⅰ期;S100P mRNA在Ⅲ期中的表达量高于Ⅰ期。(4)根据有无淋巴结转移,三者mRNA在有淋巴结转移癌组织中的表达量均高于无淋巴结转移的癌组织。(5)根据有无静脉癌栓,S100A4 mRNA在有静脉癌栓的癌组织中的表达量高于无静脉癌栓的癌组织。结论S100A4、S100A6、S100P在NSCLC中表达增加,尤其是在有淋巴结转移及TMN分期越高的癌组织中表...     

非小细胞肺癌中KLF6-SV1的表达及临床病理学意义

目的观察抑癌基因KLF6的剪切变异体KLF6-SV1在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达特点,探讨其与临床病理学参数的关系。方法应用免疫组化检测42例NSCLC和40例良性肺疾病(肺的炎性肌纤维母细胞瘤、肺脓肿、肺结核、肺的硬化性血管瘤等)中KLF6-SV1蛋白的表达水平,原位杂交检测42例NSCLC和40例良性肺疾病中KLF6-SV1基因mRNA的表达。结果 KLF6-SV1在NSCLC中的蛋白阳性率为71.4%(30/42),表达水平均高于良性肺疾病(P<0.05)。KLF6-SV1基因mRNA的阳性率为69.0%(29/42),表达水平高于良性肺疾病(P<0.05)。KLF6-SV1的蛋白表达水平与其mRNA表达水平之间具有较好的一致性。KLF6-SV1的表达与有无淋巴结转移及肿瘤的分化程度有关,组间差异具有统计学意义(P<0.05),与病理分型、组织大小和临床分期无关,组间差异不具有统计学意义(P>0.05)。结论 KLF6-SV1的过表达可能与NSCLC的发生、发展及早期淋巴结转移密切相关,有望成为今后诊断的参考指标之一,并有可能成为肿瘤基因治疗的新靶点之一。     

The expression and its clinical pathologic significance of KLF6-SV1 in non-small cell lung cancer

目的 观察抑癌基因KLF6的剪切变异体KLF6-SV1在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达特点,探讨其与临床病理学参数的关系.方法 应用免疫组化检测42例NSCLC和40例良性肺疾病(肺的炎性肌纤维母细胞瘤、肺脓肿、肺结核、肺的硬化性血管瘤等)中KLF6-SV1蛋白的表达水平,原位杂交检测42例NSCLC和40例良性肺疾病中KLF6-SV1基因mRNA的表达.结果 KLF6-SV1在NSCLC中的蛋白阳性率为71.4%(30/42),表达水平均高于良性肺疾病(P＜0.05).KLF6-SV1基因mRNA的阳性率为69.0%(29/42),表达水平高于良性肺疾病(P＜0.05).KLF6-SV1的蛋白表达水平与其mRNA表达水平之间具有较好的一致性.KLF6-SV1的表达与有无淋巴结转移及肿瘤的分化程度有关,组间差异具有统计学意义(P＜0.05),与病理分型、组织大小和临床分期无关,组间差异不具有统计学意义(P＞0.05).结论 KLF6-SV1的过表达可能与NSCLC的发生、发展及早期淋巴结转移密切相关,有望成为今后诊断的参考指标之一,并有可能成为肿瘤基因治疗的新靶点之一.     

BCRP、LUNX基因mRNA表达水平与非小细胞肺癌患者的病理类型及分期的相关性

目的探讨乳腺癌耐药蛋白(BCRP)和肺特异性X蛋白(LUNX)基因的mRNA水平与非小细胞肺癌(NSCLC)患者病理类型及分期的相关性及其对于预后的价值。方法选取2015年6月至2018年6月河南大学淮河医院收治的89例患者为NSCLC组, 以同期收治的55例肺良性病变患者为对照, 检测两组患者外周血中BCRP、LUNX的mRNA表达水平, 并分析其与临床病理特征及预后的相关性。结果 NSCLC组外周血中BCRP、LUNX mRNA的阳性表达率显著高于肺良性病变组(P<0.05);NSCLC患者BCRP mRNA的表达与分化程度、TNM分期有关(P<0.05), 与性别、年龄、吸烟、病理类型、淋巴结转移无关(P>0.05);其LUNX mRNA的表达与分化程度、TNM分期、淋巴结转移有关(P<0.05), 与性别、年龄、吸烟、病理类型无关(P>0.05);BCRP mRNA表达组与LUNX mRNA表达组的总体生存率均显著低于无表达组(P<0.05);分化程度、TNM分期、淋巴结转移、BCRP mRNA表达、LUNX mRNA表达均为影响NSCLC患...     

CYFRA21-1联合PTEN检测对非小细胞肺癌诊断价值分析

目的 探讨细胞角蛋白-19片断抗原(CYFRA21-1)和第10染色体同源丢失性磷酸酶-张力蛋白酶基因(phosphatase and tensin homolog deleted on chromosome ten,PTEN)表达在非小细胞肺癌(non-small cell lung cancer,NSCLC)诊断中的作用及其联合检测的临床价值.方法 选取126例NSCLC和同期35例良性肺疾病患者,收集患者年龄、病理类型和淋巴结转移等临床指标,电化学发光法检测血清肿瘤标志物CYFRA21-1水平,实时荧光定量PCR(quantitative real-time PCR,qPCR)法检测PTEN mRNA的表达情况.结果 肿瘤标志物结果显示,NSCLC患者组血清CYFRA21-1阳性率为75.4％,良性肺疾病患者组为54.3％,差异有统计学意义(P ＜0.05);qPCR结果显示,NSCLC组织中PTEN mRNA表达显著低于良性肺疾病患者组,差异有统计学意义(P＜0.01),且PTEN mRNA表达与临床分期和淋巴结转移显著相关(P＜0.01).结论 NSCLC患者血清CYFRA21-1水平及组织中PTEN mRNA低表达,提示CYFRA21-1联合PTEN检测将为未来NSCLC诊断方面提供新思路.     

Ephrin B2上调促进非小细胞肺癌上皮间质转化及转移

目的:探究Ephrin B2上调对非小细胞肺癌(NSCLC)上皮间质转化及转移的影响。方法:选取NSCLC组织和癌旁正常肺组织,免疫组织化学方法检测NSCLC和正常组织中Ephrin B2蛋白阳性表达率。将转染后的细胞分为4组:空白组(Blank组)、阴性对照组(NC组)、Ephrin B2 vector组、sh-Ephrin B2组。qRT-PCR和Western blot检测各组细胞Ephrin B2、Ecadherin、N-cadherin、Vimentin、MMP-2的表达水平。划痕实验检测各组转染后细胞迁移能力。结果:NSCLC组织中Ephrin B2蛋白表达显著高于正常肺组织和癌旁组织(P 0. 05)。与Blank组相比,Ephrin B2 vector组细胞迁移能力上升,Ephrin B2、Ncadherin、Vimentin、MMP-2 mRNA表达上升(P 0. 05),E-cadherin mRNA和蛋白表达水平下降(P 0. 05)。sh-Ephrin B2组细胞迁移能力下降,Ephrin B2、N-cadherin、Vimentin、MMP-2 mRNA和蛋白表达水平下降(P 0. 05),E-cadherin mRNA和蛋白表达水平上升(P 0. 05)。结论:Ephrin B2上调促进非小细胞肺癌上皮间质转化及转移。     

TIMP-3基因甲基化与结直肠癌临床病理的关系

目的：探讨TIMP-3基因甲基化与结直肠癌临床病理指标和转移复发的关系。 方法： 采用巢式甲基化特异性PCR技术（nMSP法）检测100例结直肠癌组织和100例癌旁非癌组织TIMP-3基因甲基化；采用RT-PCR检测100例结直肠癌组织和100例癌旁非癌组织TIMP-3 mRNA的表达。 结果： 肿瘤组织TIMP-3 mRNA的表达阳性率为64%，肿瘤组织TIMP-3 mRNA的表达率明显低于癌旁非癌组织（P＜0.01）；TIMP-3 mRNA的表达率无淋巴结转移组（34/42）高于淋巴结转移组（30/58）（P＜0.01），甲基化阳性率Duke’s C+D期伴淋巴结转移组明显高于Duke’s A+B期不伴淋巴结转移组（P＜0.05）。结肠近端、分化程度差的结直肠癌组织甲基化阳性率明显高于远端直肠和分化程度高者（P＜0.05）。 结论： TIMP-3基因甲基化容易发生在结肠近端、Duke’s C、D期、伴淋巴结转移、细胞分化差和浸润型结直肠癌患者。     

FRAS1蛋白与非小细胞肺癌脑转移的关系

目的:探讨FRAS1蛋白与非小细胞肺癌(NSCLC)脑转移的关系。方法:采用q PCR检测FRAS1的mRNA在NSCLC脑转移组织和同期原发灶组织中的表达水平,采用SP免疫组化法检测FRAS1蛋白在肺癌组织和癌旁非肿瘤组织的表达水平,以及有脑转移和无脑转移NSCLC原发灶组织中FRAS1蛋白的表达水平。结果:FRAS1 mRNA在肺癌脑转移灶中的表达量是肺癌原发灶中的近10倍,差异具有统计学显著性(P0.05);FRAS1蛋白在肺癌组织内表达,但在癌旁非肿瘤组织内未见表达;FRAS1蛋白在有脑转移NSCLC患者的肺癌组织中表达明显高于无脑转移NSCLC患者的肺癌组织,差异具有统计学显著性(P0.01)。结论:NSCLC组织中FRAS1蛋白表达可能与肺癌发生有关,同时肺癌组织中FRAS1蛋白高表达可能与肺癌脑转移密切相关。     

非小细胞肺癌中窖蛋白1和pERK1/2表达与预后相关性研究

目的 探讨非小细胞肺癌(NSCLC)组织窖蛋白1与pERK1/2的表达及其与预后的关系.方法 应用免疫组织化学(sP法)检测160例NSCLC及20例正常肺组织标本中窖蛋白1与pERK1/2的表达.结果 窖蛋白1在NSCLC和正常肺组织阳性率分别为65.6%(105/160)和100%(20120),P=0.002.中-高分化组和低分化组阳性率分别为56.8%(46/81)和75.7%(53/70),P=0.015;Ⅰ-Ⅱ期阳性率为58.2%(53/91),Ⅲ-Ⅳ期阳性率75.4%(52/69),P=0.024;有淋巴结转移组阳性率为77.8%(56/72),无淋巴结转移组阳性率为55.7%(49/88),P=0.003.窖蛋白1阳性患者1、3、5年生存率(71.4%、37.1%、17.1%)低于阴性患者(89.1%、69.1%、43.6%),P=0.000.pERK1/2在NSCLC和正常肺组织阳性率分别为61.3%和0,P=0.000;中-高分化组和低分化组阳性率分别为53.1%(43/81)和71.4%(50/70),P=0.021;Ⅰ-Ⅱ期阳性率为49.5%(45/91),Ⅲ-Ⅳ期阳性率76.8%(53/69),P=0.000;有淋巴结转移组阳性率为80.6%(58/72),无淋巴结转移组阳性率为45.5%(40/88),P=0.000.pEBK1/2阳性患者1、3、5年生存率(74.5%、42.9%、19.4%)低于阴性者(82.3%、56.5%、37.1%),P=0.002.窖蛋白1与pERK1/2负相关,P=0.000.结论 窖蛋白1在NSCLC中低表达,pEBK1/2在NSCLC中高表达.窖蛋白1蛋白阳性表达和pEBK1/2蛋白高表达与NSCLC的发生及侵袭、转移相关.窖蛋白1和pERK1/2可作为NSCLC一个预后预测的指标.     

非小细胞肺癌中KiSS-1、MMP-2和MVD的表达及意义

目的探讨肿瘤转移抑制基因亲吻素-1(Kisspeptin 1,KiSS-1)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和微血管密度(microvessel density,MVD)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及与预后的关系。方法采用免疫组化SP法检测KiSS-1、MMP-2、MVD在NSCLC组织中的表达;应用ELISA法检测MMP-2在血清中的表达;并探讨三者与患者术后5年生存期的关系。结果97例NSCLC组织中KiSS-1在Ⅰ+Ⅱ期、无淋巴结转移组中的表达与Ⅲ+Ⅳ期、有淋巴结转移组相比,差异有统计学意义(P<0.05);MMP-2在肿瘤直径>3 cm、腺癌组、Ⅲ+Ⅳ期、有淋巴结转移组中的表达与肿瘤直径≤3 cm、鳞癌组、Ⅰ+Ⅱ期、无淋巴结转移组相比,差异有统计学意义(P<0.05);MVD在Ⅲ+Ⅳ期、有淋巴结转移组中的表达分别高于Ⅰ+Ⅱ期、无淋巴结转移组(P<0.05)。NSCLC患者5年生存期与KiSS-1的高表达、MMP-2低表达和MVD低表达呈正相关(P<0.05)。结论KiSS-1、MMP-2和CD34在NSCLC的发生、浸润和转移过程中发挥重要作用,三者可作为肿瘤恶性程度的评判指标。     

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.     

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.