p53、EGFR和Ki-67抗原在子宫恶性中胚叶混合瘤中的表达

目的：研究子宫恶性中胚叶混合瘤ｐ５３、ＥＧＦＲ和Ｋｉ－６７抗原的表达及与肿瘤临床分期、组织学分级和预后的关系。方法：用免疫组化Ｓ－Ｐ法对２１例子宫恶性中胚叶混合瘤的存档资料作染色观察。结果：ｐ５３、ＥＧＦＲ和Ｋｉ－６７抗原的阳性表达率分别为６１．９％、６１．９％和７１．４％。临床分期Ⅱ～Ⅳ期肿瘤（１０／１２）的ｐ５３阳性表达率明显高于Ⅰ期肿瘤（３／９）（Ｐ＜０．０５）、肿瘤癌性成分Ⅱ级的ｐ５３阳性表达高于Ⅰ期（Ｐ＜０．０５）。６例在１年内死亡的病例，其中５例ｐ５３阳性染色，而５例生存２年以上的肿瘤ｐ５３免疫染色全部阴性，两组比较（Ｐ＜０．０５）。肉瘤成分Ⅲ级的ＥＧＦＲ阳性率高于Ⅱ级（Ｐ＜０．０５），除此而外，ＥＧＦＲ和Ｋｉ－６７的表达和肿瘤分期、预后均无相关性。结论：肿瘤的ｐ５３表达具有预后意义     

大肠癌表皮生长因子受体和p53蛋白表达与临床病理特征和预后的关系

为了研究大肠癌表皮生长因子受体（ＥＧＦＲ）和ｐ５３蛋白表达与病理特征和预后的关系，应用免疫组化检测ＥＧＦＲ和ｐ５３在６１例大肠癌中的表达。结果提示：正常大肠粘膜未发现ＥＧＦＲ和ｐ５３阳性表达，而两者在大肠癌均有较高表达（７７．０４％和５５．７５％）。ＥＧＦＲ表达与大肠癌Ｄｕｋｅｓ分期有关（Ｐ＜０．０５）。ｐ５３表达与大肠癌分化程度及Ｄｕｋｅｓ分期有关（Ｐ＜０．０５）。大肠癌生存率随ＥＧＦＲ和ｐ５３表达增高而降低，其中两者４年生存率＞６５％表达组均明显低于＜２５％组（Ｐ＜０．０５），ＥＧＦＲ－ＬＩ和ｐ５３－ＬＩ与生存期均有明显负相关。结果表明：ＥＧＦＲ和ｐ５３表达与大肠癌的进展程度有关，该两项指标对大肠癌临床诊治和预后的评估有重要价值。     

大肠癌表皮生长因子受体和p53蛋白表达与临床病理特？…

为了研究大肠癌表皮生长因子受体（ＥＧＦＲ）和ｐ５３蛋白表达与病理特征和预后的关系，应用免疫组化检测ＥＧＦＲ和ｐ５３在６１例大肠癌中的表达，结果提示：正常大肠粘膜未发现ＥＧＦＲ和ｐ５３阳性表达，而两者在大肠癌均有较高表达（７７．０４％和５５．７５％）。ＥＧＦＲ表达与大肠癌Ｄｕｋｅｓ分期有关（Ｐ〈０．０５）。ｐ５３表达与大肠癌分化程度及Ｄｕｋｅｓ分期有关（Ｐ〈０．０５）。大肠癌生存率随ＥＧＦＲ和ｐ５３     

胃癌p53、nm23和EGF-R蛋白表达与临床病理特征的关系

目的：探讨ｐ５３、ｎｍ２３和ＥＧＦ－Ｒ蛋白表达与胃癌临床病理特征的关系。方法：运用免疫组织化学方法研究５７例胃癌、２０例异型增生和２０例肠上皮化生和１０例正常胃粘膜ｐ５３、ｎｍ２３和ＥＧＦ－Ｒ蛋白的表达。结果：正常胃粘膜三种蛋白均阴性，肠上皮化生ｐ５３和ｎｍ２３均未表达，而ＥＧＦ－Ｒ阳性率为５％。异型增生和胃癌组织中ｐ５３阳性率分别为１５％和５４．４％；ｎｍ２３阳性率分别为５％和６３．２％；ＥＧＦ     

甲状腺乳头状腺癌中EGFR、nm23-H1和p53蛋白的表达

目的：探讨 Ｅ Ｇ Ｆ Ｒ、ｎｍ２３ Ｈ１ 及ｐ５３ 蛋白在甲状腺乳头状腺癌中的表达及其与淋巴结转移的关系。方法：应用免疫组化 Ａ Ｂ Ｃ 法检测３６ 例有颈淋巴结转移的甲状腺乳头状腺癌的原发灶与转移灶和４０ 例无转移的甲状腺乳头状腺癌中 Ｅ Ｇ Ｆ Ｒ、ｎｍ２３ Ｈ１ 及ｐ５３ 蛋白的表达。结果：７６ 例甲状腺乳头状腺癌的 Ｅ Ｇ Ｆ Ｒ、ｎｍ２３ Ｈ１ 及ｐ５３ 蛋白的阳性表达率分别为５５３ ％ 、６０５ ％ 和１１８ ％ ;但有转移的甲状腺乳头状腺癌的 Ｅ Ｇ Ｆ Ｒ 阳性表达率高于无转移者（ Ｐ＜ ００５） ,且转移灶的 Ｅ Ｇ Ｆ Ｒ 阳性率明显高于其原发灶（ Ｐ＜ ００５） ;有转移的甲状腺乳头状腺癌的ｎ ｍ２３ Ｈ１ 阳性率低于无转移癌者（ Ｐ＜ ００１） ;甲状腺乳头状腺癌中 Ｅ Ｇ Ｆ Ｒ 的阳性表达与ｎ ｍ２３ Ｈ１ 的表达有负相关（ Ｐ＜ ００１） 。结论：甲状腺乳头状腺癌 Ｅ Ｇ Ｆ Ｒ 的过表达,ｎｍ２３ Ｈ１ 的低表达,二者表达的失平衡是其易于淋巴结转移的原因之一, Ｅ Ｇ Ｆ Ｒ,ｎｍ２３ Ｈ１ 联用可作为甲状腺乳头状腺癌淋巴结转移的评价指标。     

表皮生长因子受体在口腔鳞癌组织中的表达及意义

目的：研究表皮生长因子受体（ＥＧＦＲ）在口腔鳞癌组织中的表达及其临床病理学意义。方法：采用免疫组化Ｓ－Ｐ法对６５例不同分化的口腔鳞癌组织及１０例正常口腔粘膜组织进行ＥＧＦＲ检测。结果：ＥＧＦＲ在鳞癌组织中呈异质性表达,其阳性率（６１．５％）明显高于正常口腔粘膜组织（Ｐ〈０．０１）;ＥＧＦＲ表达状况与鳞癌组织学分级,区域淋巴结转移及患者预后间存在相关关系（Ｐ〈０．０１或０．０５）。结论：ＥＧＦＲ在口     

大肠腺瘤与腺癌P21,P53,P185蛋白表达及ras,p53基因突变的检测

应用免疫组化及ＰＣＲ－ＲＦＬＰ法检测３０例大肠腺瘤、７４例大肠腺癌及癌旁粘膜Ｐ２１、Ｐ５３、Ｐ１８５蛋白表达及ｒａｓ、ｐ５３基因突变。结果表明，大肠腺瘤Ｐ２１、Ｐ５３蛋白阳性率（５３．３％，２７．６％）高于癌旁粘膜（Ｐ＜０．０１），二者过度表达与腺瘤恶性倾向有关。大肠腺癌Ｐ２１、Ｐ５３及Ｐ１８５蛋白阳性率（７２．９％，３７．８％，４７．２％）皆高于腺瘤Ｉ级不典型增生（Ｐ＜０．０１，Ｐ＜０．０５及Ｐ＜０．０５）。９例腺瘤，４０例腺癌存在两种以上蛋白表达，共同表达与腺瘤恶性倾向及腺癌预后有关。大肠腺瘤及腺癌ｒａｓ基因突变率分别为２６．７％及４１．９％，ｒａｓ基因突变与腺瘤恶性倾向有关。大肠腺瘤及腺癌ｐ５３基因２４８位点突变率分别为３．３％及１４．９％。６例腺癌存在两种基因突变，两种基因协同突变与大肠癌预后有关。提示ｒａｓ、ｐ５３及ｃ－ｅｒｂＢ－２基因改变均参与了大肠癌的发生、发展过程。     

p53、p21、p185蛋白表达与横纹肌肉瘤分化及预后的关系

目的研究ｐ５３、ｒａｓ和ｃ－ｅｒｂＢ－２癌基因蛋白产物ｐ２１、ｐ１８５在横纹肌肉瘤（ＲＭＳ）中的表达及其与ＲＭＳ的分型、分级和预后的关系。方法对确诊的５０例中的４１例有随访的ＲＭＳ用免疫组化ＡＢＣ法标记ｐ５３、ｐ２１、ｐ１８５蛋白，结果发现ｐ５３、ｐ２１、ｐ１８５在ＲＭＳ的阳性率分别为７２％、６８％、６０％，其阳性表达与年龄、性别和ＲＭＳ的组织类型差异无显著性（Ｐ＞０．０５）；但与分化程度有关，其中ｐ５３、ｐ２１在低分化ＲＭＳ的阳性率分别为８５％和８０％，显著高于高分化ＲＭＳ的４２．９％和２８．６％（Ｐ＜０．０５）；ｐ５３蛋白在有转移组ＲＭＳ的阳性率为８６．４％，显著高于无转移组６０．７％（Ｐ＜０．０５）；有随访的４１例病例中。存活１年的ｐ５３蛋白阳性率为８６．７％，显著高于３年的４１．７％（Ｐ＜０．０５）。结论ｐ５３、ｐ２１蛋白表达可作为肿瘤分化及恶性程度的评价指标，而ｐ５３更能反映肿瘤预后，是肿瘤预后差的重要指标之一。     

肝细胞癌及癌旁肝组织中bcl—2和p53蛋白表达与？…

目的：探讨ｂｃｌ－２和ｐ５３蛋白的表达与端粒酶活性的相关性及其与ＨＣＣ发生的关系。方法：利用端粒酶原位标记法显示端粒酶活性,采用Ｓ－Ｐ法免疫组化技术的检测ｂｃｌ－２和ｐ５３蛋白。结果：端粒酶在ＨＣＣ中的阳性率（９１．７％）显著高于癌旁肝组织（５８．３％）（Ｐ〈０．０５）,端粒酶活性强度与ＨＣＣ分化程度无关（Ｐ〉０．０５）;癌组织中ｂｃｌ－２和ｐ５３蛋白的阳性率均高于癌旁组织（Ｐ〈０．０１）;ＨＣＣ     

肺癌中MTS1/p16和p53基因产物的表达与细胞增殖的关系

目的：研究肺癌中ＭＴＳ１／ｐ１６和ｐ５３基因产物的表达与细胞增殖的关系。方法：应用Ｓ－Ｐ免疫组织化学方法研究６２例肺癌组织中ｐ１６蛋白和ｐ５３蛋白的表达情况，并进行增殖细胞核抗原（ＰＣＮＡ）检测，计算细胞增殖指数（ｐｒｏｌｉｆｅｒａｔｉｏｎｉｎｄｅｘ，ＰＩ）。结果：６２例肺癌组织中ｐ１６蛋白和ｐ５３蛋白阳性率分别为５８．１％和５９．７％。腺癌ｐ１６蛋白的阳性率明显高于小细胞癌（Ｐ＜０．０５）；淋巴结转移阳性组ｐ１６蛋白的表达显著低于阴性组（Ｐ＜０．０５）；ＰＩ分级为Ⅱ级的ｐ１６蛋白表达显著高于Ⅳ级（Ｐ＜０．０５）。不同组织类型肺癌中ｐ５３蛋白的表达未见明显差异，淋巴结转移阳性组ｐ５３蛋白的表达高于阴性组（Ｐ＜０．０１）；不同ＰＩ分级中ｐ５３蛋白的表达，Ⅳ级明显高于Ⅰ级（Ｐ＜０．０５）和Ⅱ级（Ｐ＜０．０５），Ⅲ级明显高于Ⅰ级（Ｐ＜０．０５）和Ⅱ级（Ｐ＜０．０１）。ｐ１６蛋白低表达和ｐ５３蛋白过表达之间未见明显相关。结论：ｐ１６蛋白低表达和ｐ５３蛋白过表达均有促进肺癌细胞增殖的作用，ｐ１６蛋白的表达与肺癌的细胞分化有关，ｐ５３蛋白过表达对肺癌细胞的转移起重要作用。抑癌基因ｐ５３对ＭＴＳ１／ｐ１６基因无明显调控作     

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.