子宫颈鳞状上皮内瘤变及鳞状细胞癌中间质细胞CD34、α-SMA的表达及意义

目的探讨CD34和平滑肌肌动蛋白（α-SMA）在宫颈各种病变间质细胞中的表达及其在宫颈癌早期浸润诊断中的价值。方法应用免疫组化SP法检测78例宫颈各种病变组织（正常10例、低级别CIN15例、高级别CIN16例、宫颈癌伴早期浸润15例、宫颈癌22例）的间质细胞中CD34、α-SMA的表达。结果CD34在所有正常宫颈和低级别CIN间质细胞中均表达,高级别CIN阳性表达率为87．5％（14／16）,而在宫颈癌伴早期浸润和宫颈癌中阳性表达率分别为40％（6／15）和40．9％（9／22）,宫颈癌伴早期浸润和癌组织明显低于正常、低级别和高级别CIN（P〈0．05）。α-SMA在正常宫颈间质细胞中无表达,低级别和高级别CIN阳性表达率分别为13．3％（2／15）和81．3％（13／16）,而所有宫颈癌伴早期浸润和宫颈癌间质细胞中均有α-SMA的表达,高级别CIN、宫颈癌伴早期浸润和宫颈癌高于低级别CIN（P〈0．05）。结论宫颈间质细胞。CD34表达缺失和α-SMA表达获得与宫颈鳞状上皮的恶性转化密切相关。检测宫颈病变中间质细胞CD34和α-SMA的表达有助于在小的活检标本中宫颈早期浸润癌和宫颈癌的诊断。     

胃癌间质中肿瘤相关纤维母细胞CD34和SMA的表达及意义

目的探讨胃癌间质中肿瘤相关纤维母细胞CD34和SMA的表达及与胃癌侵袭性的关系。方法应用免疫组织化学PV6000通用型二步法检测75例胃癌组织及10例正常胃黏膜组织中间质纤维母细胞CD34和SMA的表达,并分析其与胃癌临床病理特征的关系。结果CD34在正常胃黏膜组织纤维母细胞中阳性表达率为80.0%（8/10）,而在胃癌组织纤维母细胞中仅6/75例呈阳性表达（8.0%）,两者比较差异有显著性（P〈0.01）。胃癌组织纤维母细胞中SMA阳性表达率为90.7%（68/75）,显著高于正常胃黏膜组（30.0%）（P〈0.01）。胃癌组织纤维母细胞中SMA表达与胃癌的Lauren分型及组织学分级无关（P〉0.05）,与临床分期和淋巴结转移有关（P〈0.05）,Ⅲ-Ⅳ期强阳性率（75.6%）明显高于Ⅰ-Ⅱ期（26.7%）（P〈0.01）,有淋巴结转移组的强阳性率（78.7%）明显高于无淋巴结转移组（17.9%）（P〈0.01）。结论与正常组织中纤维母细胞相比,胃癌中纤维母细胞表现为CD34（＋）表达的缺失,而转变为SMA（＋）的肌纤维母细胞的特征,两者的联合检测将可能作为肿瘤相关纤维母细胞较特异的标记;肿瘤相关纤维母细胞与胃癌的侵袭转移密切相关。     

结直肠癌CD44V6、E-cadherin和VEGF的表达及其意义

目的：探讨结直肠癌CD44V6、E-cadherin和VEGF的表达及其临床意义。方法：应用免疫组化S－P法检测46例结直肠癌CD44V6、E-cadherin和VEGF的表达，并分析其与结直肠癌临床病理特征的关系。同时检测了23例淋巴结转移灶CD44V6、E-cadherin和VEGF的表达。结果：结直肠癌组织中CD44V6、E-cadherin和VEGF阳性表达率分别为50．0％、56．5％、和50．0％；原发灶CCD4V6和VEGF阳性表达率低于淋巴结转移灶（60．9％和56．％），而原发灶E-cadherin阳性表达率则高于淋巴结转移灶（43．5％）。结直肠癌CDV46和VEGF阳性表达与淋巴结转移，局部浸润深度和Dukes分期等有关。E-cadherin阳性表达与结直肠癌临床病理特征无关。结论：CD44V6和VEGF是结直肠癌发生与发展重要的促进因子，其过度表达与结直肠癌浸润转移，病理分期有关，可作为预测结直肠癌预后的生物学指标之一。     

胸苷磷酸化酶在结直肠癌中的表达及与血管生成的关系

目的：研究结直肠癌组织中胸苷磷酸化酶（thymidine phosphorylase,TP)表达与癌组织分化程度，淋巴结转移及肿瘤内微血管密度（MVD）的关系。方法：对50例结直肠癌标本及21例正常结直肠黏膜组织进行免疫组化S－P法测定癌组织中TP的表达情况；通过CD34免疫组化染色检测癌组织中的MVD。结果：结直肠癌细胞的TP表达阳性率高于正常结直肠黏膜上皮（P＜0．01）；TP阳性组中局部淋巴结转移率高TP阴性组；TP阳性组的MVD高于TP阴性组；它们的差别均具有统计学意义，结直肠癌中高、中、低分化癌组之间的TP阳性率无明显差异。结论：癌细胞中TP的表达与肿瘤的血管生成及淋巴结转移有关。但与结直肠癌的组织化学级别无关。     

整合素连接激酶在梗阻性肾病肾小管上皮细胞转化中的作用

目的观察整合素连接激酶（ILK）在单侧输尿管梗阻小鼠（UUO）肾脏中的表达,并探讨其在肾小管上皮细胞转化中的作用。方法将10周龄健康雄性CD-1小鼠随机分为假手术组（C,n=20）和UUO组（n=40）,分别于术后1、3、7、14d处死小鼠。采用Masson染色观察肾间质纤维化程度;用免疫组织化学（sP法）的方法观察ILK、E-钙黏蛋白（E-cadherin）和α-平滑肌肌动蛋白（α-SMA）的表达;Westernblot半定量分析梗阻侧肾组织ILK的蛋白水平;用即时荧光逆转录聚合酶链反应（RT-PCR）检测ILK、E-cadherin和α-SMA mRNA的表达。结果免疫组织化学显示ILK在假手术组只有微量表达,主要位于肾小球脏层上皮细胞,UUO术后1d ILK蛋白表达显著增多（t=16．5,P＜0．01）,7d达高峰。术后3d肾小管上皮细胞及肾间质α-SMA阳性细胞数显著增多（t=21．0,P＜0．01）,肾小管上皮细胞表达E-cadherin明显减少（t=5．6,P＜0．01）。根据免疫组织化学结果分析,术后1～7d,ILK蛋白表达与α-SMA蛋白表达呈正相关（R=0．88,P＜0．01）,与E-cadherin表达呈负相关（R=-0．87,P＜0．01）。Westernblot结果显示ILK蛋白表达于术后1d明显增加,7d达高峰,14d表达不再增加（P＞0．05）。RT-PCR结果显示术后1d ILK mRNA表达增多（t=141．6,P＜0．01）,E-cadherin mRNA表达于术后3d显著减少（P＜0．01）,α-SMA mRNA表达于术后3d开始增多（P＜0．01）。结论UUO模型早期整合素连接激酶表达增高,可能通过介导肾小管上皮细胞．间充质转化而参与肾脏纤维化的发生发展。     

微淋巴管和微血管密度对结直肠癌的预后意义

目的观察微淋巴管密度（MLD）和微血管密度（MVD）在结直肠癌中的分布特点,探讨其转移与预后意义。方法利用淋巴管和血管特异标记物Podoplanin和CD34行免疫组化EnVision法检测227例结直肠癌及正常黏膜,观察MLD、MVD分布特点,分析其与临床病理参数之间的关系。结果结直肠癌前缘区MLD（19．64±7．21）高于肿瘤中央区MLD（5．64±2．87）和正常黏膜MLD（13．30±3．06）;肿瘤前缘区MVD（40．93±11．71）亦高于肿瘤中央区MVD（21．07±8．38）和癌旁正常黏膜（29．32±11．69）,差异有统计学意义（P〈0．05）。结直肠癌前缘区MLD与肿瘤浸润深度、淋巴管侵犯、淋巴结转移及远处器官转移等临床病理参数相关,差异有统计学意义（P〈0．05）。肿瘤前缘区MLD、MVD增高与结直肠癌的不良预后密切相关（P〈0．05）,但不是独立预后因素。结论结直肠癌微淋巴管和微血管分布以肿瘤前缘区最为密集,且前缘区MLD和MVD增高是评估结直肠癌预后不良的指标。     

环氧化酶-2在结直肠癌组织中的表达及其临床意义

目的：探讨环氧化酶-2（COx-2）在结直肠癌组织中的表达及其临床意义。方法：采用链霉素抗生物素卵白素-过氧化物酶（SP）法进行免疫组化染色，观察43例结直肠癌组织和14例正常大肠组织中COX-2的表达情况。结果：COX-2在83．72％的结直肠癌组织中表达，仅在14．29％的正常大肠组织中表达（P〈0．005）。COX-2表达水平与肿瘤Duke’s分期、大小、淋巴结转移呈正相关（P〈0．05），而与肿瘤分化程度、位置、浸润深度及患者性别无明显相关性（P〉0．05）。结论：COX-2在结直肠癌组织中过表达，可能在结直肠癌的发生发展中起重要作用。     

结直肠癌中TAZ和β-catenin的表达及意义

目的：观察TAZ和β-catenin蛋白在结直肠癌中的表达,探讨二者与结直肠癌发生、发展的关系。方法应用免疫组化EnVision两步法检测168例结直肠癌组织和30例正常肠黏膜组织中TAZ和β-catenin的表达。结果结直肠癌组织中TAZ的阳性率显著高于正常肠黏膜组织(P<0．01),其表达与病理学分级、浸润深度、淋巴结转移、TNM分期相关(P<0．05),TAZ阳性组的5年生存率显著低于TAZ阴性组( P<0．05);结直肠癌组织中β-catenin异常表达率显著高于正常肠黏膜组织( P<0．01),其异常表达与肿瘤浸润深度、淋巴结转移、TNM分期相关(P<0．05);β-catenin异常表达组的5年生存率显著低于β-catenin正常表达组(P<0．05);结直肠癌中TAZ阳性表达和β-catenin异常表达呈正相关(P<0．01)。结论 TAZ表达增高和β-catenin异常表达在结直肠癌发生、发展中具有重要作用,检测TAZ和β-catenin的表达可作为判断结直肠癌的生物学行为和判断预后的指标。     

结直肠癌中TGF-β1表达与肿瘤浸润转移和血管形成的关系

目的　探讨结直肠癌中转化生长因子 β1(TGF β1)的表达与肿瘤浸润转移和血管形成的关系。 方法　免疫组化S P法检测 12 6例结直肠癌中TGF β1和血管内皮生长因子 (VEGF)的表达 ,同时应用CD34标记肿瘤间质中微血管密度 (MVD)。结果　 12 6例结直肠癌中TGF β1和VEGF的阳性表达率分别为 4 2 1%和 6 3 5 %。结直肠癌中TGF β1、VEGF蛋白的表达和MVD与肿瘤的浸润深度、淋巴结转移和Dukes分期呈正相关 (P <0 0 5 ) ;VEGF在TGF β1表达阳性的结直肠癌中的阳性表达率高于TGF β1表达阴性的结直肠癌 (P <0 0 5 ) ,TGF β1表达阳性的结直肠癌MVD高于TGF β1表达阴性的结直肠癌(P <0 0 5 )。结论　TGF β1可能通过间接或直接刺激肿瘤血管形成而促进结直肠癌的浸润转移     

胃癌组织中肝细胞抗原的表达及其临床意义

目的 探讨肝细胞抗原（hepatoeyte antigen,Hep）在胃癌组织中的表达及其临床意义。方法 应用免疫组织化学方法EnVision法检测88例胃癌组织中Hep的表达。结果 胃癌组织中Hep的阳性表达率为54．5％（48／88）。Hep的阳性表达在肠型胃癌中明显高于弥漫型胃癌（P〈0．05）;随着临床分期的增高,Hep的阳性表达率呈下降趋势,差异有显著性（P〈0．05）;胃癌组织中Hep的表达与患者的年龄有关（P〈0．05）,与性别、肿瘤大小、部位、浸润深度、淋巴结转移和血管侵犯均无相关性（P〉0．05）。结论 检测胃癌组织中Hep的表达可一定程度地反映胃癌的组织学分型和患者的预后。     

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.