碱性成纤维细胞生长因子在膀胱移行细胞癌中的表达

目的　研究碱性成纤维细胞生长因子 (bFGF)在膀胱移行细胞癌 (BTCC)中的表达及其意义。方法　SP法 ,对 5 5例BTCC及 10例正常膀胱组织中bFGF进行检测。结果　在正常移行细胞呈阴性表达 ,在BTCC中呈不同程度的阳性表达 ,且过表达率在不同病理分级、临床分期组间有显著性差异 (P <0 .0 5 ) ,复发组的阳性表达率明显高于初发组 (P <0 .0 5 )。结论　bFGF在BTCC侵润转移过程中起重要作用 ,BFGF表达可成为判断肿瘤预后的一项指标     

VEGF/VEGFR在膀胱癌中表达的研究

目的：探讨血管内皮细胞生长因子（VEGF）和血管内皮细胞生长因子受体（VEGFR）KDR在膀胱移行细胞癌（TCC）患者的组织标本及正常膀胱黏膜组织中的定位及表达情况.方法：分别采用免疫组化SABC法和TUNEL法检测60例膀胱癌组织,并以40例正常膀胱黏膜组织作为对照,比较两种不同组织中VEGF及KDR的阳性表达率和表达强度的差异.结果：在60例膀胱TCC中,VEGF和KDR分别有53例和51例呈阳性表达,平均表达率分别为88%和85%,随肿瘤病理分期和细胞分级的增高其表达水平上调.但在40例正常对照组中无一例表达.两者分别比较,差异均极显著（P＜0.01）.结论：VEGF可能通过膀胱移行细胞上的相应受体而发挥一定的生物学作用.膀胱TCC患者的肿瘤组织中KDR的表达可能直接诱发了肿瘤血管的形成.     

膀胱移行细胞癌中fhit基因和survivin基因的表达和意义

目的探讨fhit基因和survivin基因在膀胱移行细胞癌中的表达和意义。方法用免疫组化S-P法检测62例膀胱移行细胞癌组织及10例正常膀胱粘膜组织中fhit蛋白和survivin蛋白的表达。结果10例正常膀胱粘膜组织中fhit蛋白表达均为阳性，survivin蛋白表达均为阴性；fhit蛋白在膀胱移行细胞癌中阳性表达率为46．77％（29／62），肿瘤不同分级中随恶性程度的增长表达减少，Ⅰ级与Ⅲ级比较，差异有统计学意义（P〈0．05），不同临床分期中随分期的增长表达减少，Tis～T1与T2～T4比较，差异无统计学意义（P〉0．05）；survivin蛋白在膀胱移行细胞癌中阳性表达率为56．5％（35／62），肿瘤不同分级中随恶性程度的增高表达增高（P〈0．05），不同临床分期中随分期的增长表达增高，差异有统计学意义（P〈0．05）；fhit蛋白和survivin蛋白表达相关（P〈0．05）。结论Fhit基因和survivin基因在膀胱移行细胞癌的发生、发展过程中起着重要的作用。Fhit基因可能通过肿瘤凋亡抑制途径发挥作用的。     

P504S在前列腺癌、肾细胞癌和膀胱尿路上皮癌中的表达及临床意义

目的：探讨肿瘤标记物P504S在前列腺癌(prostate cancer,Pca)、肾细胞癌(renal cell carcinoma, RCC)和膀胱尿路上皮癌(bladder transitional cell carcinoma,BTCC)组织中的表达及临床意义。方法：采用免疫组织化学标记菌葡萄聚糖聚合物法(labeled dextran polymer,LDP),检测P504S在前列腺癌、肾细胞癌和膀胱尿路上皮癌组织中的表达情况,探讨其在前列腺增生(benign prostatic hyperplasia,BPH)组织、正常肾组织和正常膀胱组织中的表达并作相应比较。结果：P504S在Pca、RCC和BTCC组织中阳性表达率分别为93.10%、65.28%和46.07%,而在BPH、正常肾组织和正常膀胱组织分别为0%、6.67%和6.25%,各组间差异均有统计学意义(P<0.01);P504S阳性表达水平与Pca、RCC及BTCC病理分级和临床分期均呈正相关(P<0.05),与肿瘤的预后也密切相关。结论：P504S的表达水平可较好地反映前列腺癌、肾细胞癌和膀胱尿路上皮癌生物学行为,可作为判断肿瘤侵袭、病情发展及预后指标之一。     

hTERT、c-myc、Ki-67在肝癌组织中的表达及意义

目的:探讨端粒酶逆转录酶(hTERT)、c-myc、Ki-67与肝癌临床病理特征的关系以及3个因子之间的相互关系.方法:采用免疫组织化学方法检测37例肝癌组织、5例正常肝组织中hTERT和c-myc、Ki-67的表达,并进行对比研究.结果:肝癌组织中hTERT、c-myc、Ki-67阳性表达率明显高于正常肝脏组织,差异均具有统计学意义(P<0.05);hTERT、c-myc、Ki-67在肝癌组织中的表达强度均与年龄、性别、转移及肿瘤体积无关(P＞0.05),而三者表达强度均随肝癌组织学分化程度下降而明显增强;hTERT的表达强度分布与c-myc表达强度分布不相关;hTERT与 Ki-67的表达强度相关,随hTERT表达强度增加,Ki-67强度随之增加;c-myc与Ki-67的表达强度相关,随c-myc表达强度增加,Ki-67表达强度随之递增.结论:hTERT、c-myc、Ki-67的高表达在肝癌的发生发展过程中起重要作用;三者在肝癌组织中的表达关系密切.     

RIN1在膀胱尿路上皮癌中的表达及临床特征

目的探讨膀胱尿路上皮癌中RINl蛋白的表达与临床病理学特征的关系。方法用sP免疫组化法检测手术切除的88例原发性膀胱尿路上皮癌标本和20例癌旁正常组织标本。所有组织用10％福尔马林固定。石蜡包埋,连续切片,厚度4μm。所有上述患者术前均未接受放疗,化疗。通过卡方检验,分析RINl表达与膀胱尿路上皮癌的临床病理学特点。结果免疫组化法发现,88例膀胱尿路上皮癌中有49例RINl表达升高,20例癌旁组织的RINl表达正常。RINl的表达与肿瘤的病理分级（P〈0．05）和临床分期（P〈0．05）呈正相关,与年龄、性别、肿瘤大小、是否多发则无相关性（P〉0．05）。结论RINI在膀胱尿路上皮癌中存在高表达,且在膀胱癌中发挥着重要作用。     

一氧化氮合酶(NOS)在膀胱移行细胞癌中的表达及其意义

目的检测膀胱移行细胞癌中一氧化氮合酶(nitric oxide synthase,NOS)的表达,并分析其表达与肿瘤病理特性的关系.方法采用免疫组织化学技术检测35例膀胱移行细胞癌标本、12例癌旁粘膜标本及8例正常膀胱粘膜标本中一氧化氮合酶三种亚型的表达情况.结果 35例肿瘤标本中nNOS、iNOS、eNOS阳性表达率分别为74.3%、85.7%、42.9%,膀胱移行细胞癌中iNOS表达较正常膀胱粘膜增高.但移行细胞癌、癌旁粘膜、正常粘膜三组间nNOS及eNOS表达无差别.nNOS、iNOS、eNOS表达与膀胱移行细胞癌分期分级可能无相关性.结论 iNOS在膀胱移行细胞癌中表达增高,可能参与膀胱移行细胞癌的发生发展.     

膀胱移行细胞癌中PTEN的表达分析

目的研究PTEN在膀胱移行细胞癌（TCC）中的表达。方法应用免疫组织化学染色方法观察52例TCC标本PTEN的表达情况。结果TCC组中PTEN的阳性表达率为71.2%,而10例正常膀胱粘膜组织PTEN表达均为阳性。PTEN表达与膀胱肿瘤病理分级、临床分期密切相关。结论PTEN的异常表达在TCC的发生、发展过程中起重要作用。该指标的检测有助于预后判断。     

膀胱移行细胞癌中促红细胞生成素及其受体的表达

目的探讨促红细胞生成素（EPO）及其受体（EPOR）在膀胱移行细胞癌（TCC）组织中的表达,并探讨其临床意义。方法应用免疫组织化学方法、RT-PCR方法检测70例膀胱TCC组织、15例癌旁组织、10例正常膀胱组织中EPO和EPOR的蛋白和 mRNA的表达。结果70例膀胱TCC组织有44例（62.9%）EPO蛋白阳性表达,有29例（41.4%）EPOR蛋白阳性表达;15例膀胱TCC癌旁组织及10例正常膀胱组织均未见EPO、EPOR蛋白的表达。EPO蛋白表达强度与膀胱TCC的组织学分级相关（rs=0.329,P〈0.05）,而与临床分期则无明显的相关性。膀胱癌组织中EPO与EPOR表达具有相关性（rs=0.346,P〈0.01）。RT-PCR检测发现膀胱移行细胞癌组织中EPO及其受体 mRNA的表达明显高于正常膀胱组织、癌旁组织中EPO及其受体 mRNA的表达（P〈0.01）。结论EPO、EPOR在膀胱TCC组织中过表达,提示EPO、EPOR在膀胱TCC的发生、发展过程中可能起重要作用;EPO蛋白表达强度与膀胱TCC的组织学分级有明显相关性,可能成为膀胱TCC不良预后的指标之一。     

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.