自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌中的表达及意义

目的检测自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌、大肠腺瘤及正常大肠黏膜中的表达情况,探讨其与大肠癌发生、发展的相关性及意义。方法应用组织芯片技术和免疫组化SP法检测12例正常大肠黏膜、29例大肠腺瘤及115例大肠癌组织中LC3、Beclin-1、p53及BCL-2蛋白的表达水平,并结合临床病理因素进行分析。结果 LC3在大肠癌中的阳性率高于大肠腺瘤和正常大肠黏膜(P<0.01),且与大肠癌的组织学分化程度相关(P<0.05)。Beclin-1在大肠癌、大肠腺瘤组织中的表达高于正常大肠黏膜(P<0.01),但与大肠癌的组织学分化程度、Dukes分期及淋巴结转移无关(P均>0.05)。p53及BCL-2在正常大肠黏膜、大肠腺瘤及大肠癌中的表达逐渐增高(P<0.01),且与大肠癌的Dukes分期和淋巴结转移相关(P均<0.05)。经Spearman秩相关检验,Beclin-1蛋白与p53蛋白相关系数为0.224 3,成正相关表达(P<0.05)。结论在大肠癌中,自噬活性的上调与凋亡能力的下调并存;自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌的发生、发展中起协调作用,对其联合检测有助于了解和判断大肠癌的进展程度及患者的预后情况。     

RACK1在大肠癌癌变过程中的表达和意义

目的:研究RACK1蛋白在正常大肠黏膜组织、大肠癌癌前病变组织及大肠癌中的表达,初步探讨其在大肠癌发病中的作用。方法:收集92例大肠癌组织、20例大肠腺瘤组织、20例大肠炎性息肉组织和23例正常大肠黏膜组织。采用免疫组织化学方法检测RACK1在正常大肠黏膜组织、大肠癌癌前病变及大肠癌组织中的表达,统计分析RACK1表达水平与大肠癌临床病理特征之间的关系。结果:随着大肠癌癌变的演进,RACK1的表达水平进行性上调(P<0.05)。RACK1的表达水平与大肠癌患者年龄、性别、淋巴结转移及Duke分期无明显关系(P>0.05),但与大肠癌的分化程度呈正相关(P<0.05)。结论:RACK1在大肠癌癌变过程中进行性上调,其表达上调可能与大肠癌的发病有关。     

大肠癌中Bmi-1的表达及其临床病理意义

目的:研究大肠肿瘤组织中Bmi-1蛋白表达情况及其与大肠癌临床病理特征及预后的关系,并探讨Bmi-1蛋白在大肠癌中的表达与Ki67蛋白表达的关系。方法:采用免疫组织化学方法分别检测Bmi-1蛋白在60例大肠癌、30例大肠腺瘤及20例正常大肠黏膜组织3组中的表达情况及其与大肠癌临床病理特征及患者生存率的关系,并探讨大肠癌中Bmi-1 蛋白表达与Ki67蛋白的相关性。应用SPSS13.0软件包对结果进行统计学分析。结果:Bmi-1蛋白在大肠癌、大肠腺瘤及正常大肠黏膜组织中的表达率分别为25.0％、6.7％、0%, Bmi-1蛋白在大肠癌中表达明显高于腺瘤组及正常组（P＜0.05）,而在腺瘤组及正常组中的表达差异无显著（P＞0.05）;Bmi-1蛋白高表达与有无远处转移及TNM分期密切相关（P＜0.05）,而与患者性别、年龄、肿瘤大小、分布部位、分化程度、组织类型及淋巴结转移等临床病理特征无关（P＞0.05）;Kaplan-Meier生存分析显示Bmi-1蛋白高表达患者生存率明显低于低表达患者（P＜0.05）;大肠癌中Bmi-1蛋白高表达与Ki67蛋白表达无相关关系（P＞0.05）。结论:Bmi-1蛋白表达与大肠癌的发生、转移及预后关系密切,可作为评估患者侵润转移及预后的参考指标。     

stathmin和P27kip1在大肠癌中的表达及意义

目的:探讨stathmin蛋白与p27kip1蛋白在大肠癌组织中的表达及意义.方法:应用免疫组织化学SABC法检测25例正常大肠黏膜组织、25例大肠腺瘤组织、47例大肠癌组织中stathmin蛋白及p27kip1蛋白的表达情况.结果:①stathmin蛋白在正常大肠黏膜组织、大肠腺瘤组织及大肠癌组织中的阳性表达率分别为20％、48％、74.47％;正常大肠黏膜组分别与大肠腺瘤组及大肠癌组比较,差异均有统计学意义(P＜0.05);大肠腺瘤组与大肠癌组比较,差异亦有统计学意义(P＜0.05):stathmin蛋白的表达与肿瘤的分化程度、有无淋巴结转移及TNM分期显著相关(P＜0.05).②p27kap1蛋白在正常大肠黏膜组织、大肠腺瘤组织及大肠癌组织中的阳性表达率分别为92％、80％、31.91％.正常大肠黏膜组与大肠癌组比较,差异有统计学意义(P＜0.05);大肠腺瘤组与大肠癌组比较,差异亦有统计学意义(P＜0.05);正常大肠黏膜组与大肠腺瘤组比较,差异无统计学意义(P＞ 0.05);p27kip1蛋白的表达与肿瘤的分化程度及淋巴结转移有关(P＜0.05).③stathmin蛋白的表达与p27kip1蛋白的表达呈负相关(r=--0.695 3,P＜0.01).结论:stathmin蛋白在大肠癌组织中高表达,其表达程度与肿瘤的分化程度、淋巴结转移及TNM分期显著相关,p27kip1蛋白在大肠癌组织中低表达,其表达程度与肿瘤的分化程度及淋巴结转移显著相关,提示stathmin及p27kip1蛋白共同参与了大肠癌的发生、发展;stathmin蛋白可作为一种判断大肠癌恶性程度及侵袭转移的生物学指标.     

大肠癌中WIF-1和Wnt2b的表达及其临床意义

目的通过检测WIF-1与Wnt2b在正常大肠黏膜、大肠腺瘤、大肠癌中的表达及其与大肠癌生成、侵袭转移之间的关系,探讨WIF-1与Wnt2b之间的关系。方法应用免疫组化SP法检测WIF-1和Wnt2b蛋白在15例癌旁正常组织、18例大肠腺瘤和103例大肠癌组织中的表达。结果 (1)WIF-1蛋白在大肠癌中的阳性率明显低于癌旁正常组织和腺瘤;Wnt2b蛋白在大肠癌中的阳性率高于癌旁正常组织和腺瘤。(2)WIF-1在大肠癌中的表达与患者的年龄、性别、分化程度、浸润程度、淋巴转移和远处转移均无关系(P>0.05);Wnt2b在大肠癌中的表达与大肠癌的分化程度、Dukes分期、淋巴结转移和远处器官转移相关(P<0.05),而与患者的年龄、性别均无关(P>0.05)。(3)大肠癌中WIF-1与Wnt2b的表达呈负相关(r=-0.199,P<0.05)。结论 WIF-1在正常大肠组织中呈阳性表达,在大肠癌的发病机制中可能发挥一定作用;Wnt2b的表达与大肠癌的发生、侵袭转移有关,联合检测WIF-1和Wnt2b有助于大肠癌的诊断、预防和治疗。     

Expression and clinical significance of autophagy-related genes LC3,Beclin-1 and apoptosis-related genes p53,BCL-2 in colorectal carcinoma

目的 检测自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌、大肠腺瘤及正常大肠黏膜中的表达情况,探讨其与大肠癌发生、发展的相关性及意义.方法 应用组织芯片技术和免疫组化SP法检测12例正常大肠黏膜、29例大肠腺瘤及115例大肠癌组织中LC3、Beclin-1、p53及BCL-2蛋白的表达水平,并结合临床病理因素进行分析.结果 LC3在大肠癌中的阳性率高于大肠腺瘤和正常大肠黏膜(P<0.01),且与大肠癌的组织学分化程度相关(P<0.05).Beclin-1在大肠癌、大肠腺瘤组织中的表达高于正常大肠黏膜(P<0.01),但与大肠癌的组织学分化程度、Dukes分期及淋巴结转移无关(P均>0.05).p53及BCL-2在正常大肠黏膜、大肠腺瘤及大肠癌中的表达逐渐增高(P<0.01),且与大肠癌的Dukes分期和淋巴结转移相关(P均<0.05).经Spearman 秩相关检验,Beclin-1蛋白与p53蛋白相关系数为0.224 3,成正相关表达(P<0.05).结论 在大肠癌中,自噬活性的上调与凋亡能力的下调并存;自噬相关基因LC3、Beclin-1与凋亡相关基因p53、BCL-2在大肠癌的发生、发展中起协调作用,对其联合检测有助于了解和判断大肠癌的进展程度及患者的预后情况.     

Expression and clinical significance of WIF-1 and Wnt2b in colorectal carcinoma

目的 过检测WIF-1与Wnt2b在正常大肠黏膜、大肠腺瘤、大肠癌中的表达及其与大肠癌生成、侵袭转移之间的关系,探讨WIF-1与Wnt2b之间的关系.方法 应用免疫组化SP法检测WIF-1和Wnt2b蛋白在15例癌旁正常组织、18例大肠腺瘤和103例大肠癌组织中的表达.结果 (1)WIF-1蛋白在大肠癌中的阳性率明显低于癌旁正常组织和腺瘤;Wnt2b蛋白在大肠癌中的阳性率高于癌旁正常组织和腺瘤.(2)WIF-1在大肠癌中的表达与患者的年龄、性别、分化程度、浸润程度、淋巴转移和远处转移均无关系(P>0.05);Wnt2b在大肠癌中的表达与大肠癌的分化程度、Dukes分期、淋巴结转移和远处器官转移相关(P<0.05),而与患者的年龄、性别均无关(P>0.05).(3)大肠癌中WIF-1与Wnt2b的表达呈负相关(r=-0.199,P<0.05).结论 WIF-1在正常大肠组织中呈阳性表达,在大肠癌的发病机制中可能发挥一定作用;Wnt2b的表达与大肠癌的发生、侵袭转移有关,联合检测WIF-1和Wnt2b有助于大肠癌的诊断、预防和治疗.     

大肠癌相关抗原LEA在大肠癌诊断中的意义

目的:探讨LEA在大肠癌中的表达及意义。方法:采用免疫组织化学S-P法检测140例大肠癌组织和100例大肠非癌组织LEA与CEA的表达。结果:LEA表达与肿瘤分化程度有相关性,对高分化腺癌表现出更高的选择性（P<0.01）,CEA单抗对高、中、低分化腺癌选择性相似（P>0.05）,LEA在腺瘤中表达的阳性率,明显高于癌旁粘膜和正常粘膜;LEA在正常粘膜标记的阳性率明显低于CEA（P<0.05）。结论:LEA的表达与大肠癌组织的分化程度有关,LEA可作为大肠癌早期诊断的辅助指标。     

大肠腺癌和腺瘤AEG-1基因的表达及意义

目的探讨AEG-1在大肠癌中的表达及其临床病理意义。方法采用免疫组化的方法检测60例正常大肠粘膜、22例大肠腺瘤和60例大肠腺癌中AEG-1的表达。结果大肠腺癌和腺瘤中AEG-1的阳性率分别为91.7%和90.9%,明显高于正常大肠粘膜组织的23.3%,两者之间差异有统计学意义（P〈0.001）,其中大肠腺癌的中度阳性率和强阳性率分别为31.7%和60%,而大肠腺瘤分别为63.6%和27.3%,两者差异具有统计学意义（P=0.019）;对大肠腺癌中AEG-1表达与肿瘤临床病理特征做相关性分析,结果表明,AEG-1表达强度与肿瘤T、N分期显著正相关（P〈0.05）。结论 AEG-1在大肠癌和大肠腺瘤中表达增强,在大肠腺瘤恶变、大肠癌发生发展过程中发挥重要作用,可作为诊断大肠癌新的生物标记物。     

大肠腺癌中Sema4D和VEGFR2的表达及意义

目的探讨Sema4D和血管内皮生长因子受体2(VEGFR2)在大肠腺癌组织中的表达及其临床意义。方法运用组织芯片和免疫组化SP法检测115例大肠腺癌组织、19例大肠腺瘤组织和12例正常大肠黏膜组织中Sema4D与VEGFR2的表达,并分析其与临床病理特征的关系。结果 Sema4D在正常大肠黏膜表达阳性率8.33%,在腺瘤和腺癌中阳性表达率为15.79%和39.13%,差异有统计学意义且与淋巴结转移、Dukes临床分期明显相关(P<0.05)。VEGFR2在正常大肠黏膜中阳性率16.67%,在腺瘤和腺癌中表达率为21.05%和51.3%,差异有统计学意义其表达与淋巴结转移、浸润程度、Dukes临床分期明显相关(P<0.05)。结论大肠腺癌中Sema4D与VEGFR2的表达可能在大肠腺癌的发生、发展中发挥重要作用。     

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.