原发性中枢神经系统淋巴瘤9例浸润播散方式的临床病理观察

目的 探讨原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)在脑组织内浸润播散的方式.方法 复习9例PCNSL的临床病理资料,重点观察其在脑组织内浸润播散方式.结果 9例PCNSL中,8例为手术标本,1例为尸解标本,病理类型均为非霍奇金淋巴瘤,8例为弥漫大B细胞淋巴瘤,1例为非特异性外周T细胞淋巴瘤,中位年龄57岁,观察到3种基本浸润和播散方式:(1)沿血管周隙浸润,破坏血管周隙在血管周围浸润,侵入血管壁呈血管炎状改变,使血管腔闭塞.(2)沿神经束间浸润,在大脑灰质层和小脑分子层形成单个或数个细胞与脑表面垂直的条索向脑表面软脑膜下浸润.(3)上述两种方式浸润的瘤细胞最终进入脑皮质浅层和蛛网膜下腔.结论 PCNSL沿血管周隙、血管周围、神经纤维间隙等结构浸润至脑皮层浅层和蛛网膜下隙,并进一步播散.     

血管内皮生长因子和微血管密度在食管癌组织中的意义

目的 :探讨血管内皮生长因子 (VEGF)蛋白表达和微血管密度 (MVD)与食管癌临床病理的关系。方法 :应用免疫组织化学SABC法 ,以鼠抗VEGF、兔抗FⅧRAg、UEA 1抗体标记 5 2例食管癌和 5例正常食管黏膜 ,观察其在不同分化程度、浸润深度和有无淋巴结转移食管癌中的表达及MVD情况。结果 :癌组织VEGF阳性 2 8例 (5 3 9% ) ,MVD平均为 5 1 3± 14 8。VEGF蛋白表达和MVD与癌组织分化程度、淋巴结转移有关 (P <0 0 5 ,P <0 0 1) ;与癌组织浸润深度无关 (P >0 0 5 )。结论 :提示VEGF与癌组织血管发生密切相关 ,VEGF蛋白表达和MVD可作为判断食管癌的恶性程度和预后的生物学指标     

原发性中枢神经系统恶性淋巴瘤MR表现及其病理学基础

目的 研究原发性中枢神经系统恶性淋巴瘤(PCNSL)的MR表现及其病理学基础。方法 分析13例手术病理证实的原发性中枢神经系统恶性淋巴瘤的临床病理及MR表现。结果 13例中单发肿瘤4例，多发肿瘤9例，共计36个病灶。13例病变均累及幕上，其中8例病灶位于深部脑白质近脑室旁。肿瘤平均最大径为3．2cm。T1WI略低信号28个，T2WI等信号24个。28个病灶呈均匀强化。肿瘤水肿及占位效应相对较轻。2例PCNSL行MR动态增强扫描，早期强化均不明显，时间-信号强度曲线呈缓慢上升型。病理上肿瘤细胞弥漫分布，瘤细胞大小较一致，细胞质少，细胞核大，染色质颗粒粗，可见瘤细胞围绕血管呈袖套样浸润，少见明显的出血及片状坏死，未见钙化，病理均为非霍奇金淋巴瘤。结论 原发性中枢神经系统恶性淋巴瘤的病理基础决定其MR增强形态、占位程度以及肿瘤发生部位具有一定特征，运用不同的MR影像学检查方法和技术，在多数情况下可以做出术前正确诊断。     

胶质瘤中hTFERT、VEGF表达及其与肿瘤血管形成的关系

目的 探讨胶质瘤中端粒酶逆转录酶(hTERT)、血管内皮生长因子(VEGF)的表达与肿瘤血管形成问的相互关系.方法 分别用原位杂交和免疫组化染色检测106例胶质瘤hTERT和VEGF的表达;用CD34标记瘤组织血管内皮细胞,测定微血管密度(MVD).结果 hTERT、VEGF总阳性表达率分别为53.8%(57/106)、68.0%(72/106);hTERT或VEGF阳性分别定位于肿瘤细胞核内和细胞质内.hTERT阳性或VEGF阳性的瘤组织MVD分别为71.2±18.0和74.4±20.0;而相应的阴性组分别为60.3±21.8和58.4±23.1,两组差异均有显著性(P＜0.01).hTERT、VEGF的表达和MVD均与胶质瘤组织病理分级呈正相关(P＜0.01).结论 hTERT、VEGF的表达及MVD均与胶质瘤的恶性程度有关,前两者阳性表达,其MVD高于两者阴性表达,说明hTERT、VEGF在肿瘤血管形成中可能起促进作用.     

人恶性胶质瘤细胞裸鼠脑原位移植瘤FPR表达与VEGF关系

目的观测甲酰肽受体(formylpeptide receptor,FPR)在人恶性胶质瘤细胞系U87细胞裸鼠脑原位移植瘤组织中的表达,以及与血管内皮生长因子(VEGF)的关系,探讨FPR在恶性胶质瘤血管生成过程中的作用。方法培养U87细胞,以立体定向注射技术制作U87裸鼠脑原位移植瘤模型;采用间接免疫荧光染色在激光共聚焦显微镜下分别观测FPR在U87细胞和移植瘤组织的表达;免疫组化方法检测VEGF在U87细胞裸鼠脑移植瘤上的表达。结果培养的U87细胞及其原位移植瘤组织均可见FPR表达,定位于瘤细胞胞膜,VEGF阳性着色主要位于胞质,两者阳性表达程度呈正相关性。结论人恶性胶质瘤细胞系U87细胞裸鼠脑原位移植瘤组织存在FPR表达,与VEGF的产生密切相关,在胶质瘤血管生成过程中可能起重要作用。     

人脑星形细胞肿瘤IL-8的表达及其与血管生成的关系

目的：探讨IL-8,VEGF在脑胶质瘤中的表达及与血管生成的关系。方法：应用由45例人脑星形细胞肿瘤和6例正常脑组织组成的组织芯片，采用免疫组织化学技术分别进行IL-8，VEGF，CD34标记并进行半定量，观测在不同病理分级胶质瘤中的表达及与微血管密度（MVD）之间的关系。结果：6例正常脑组织中不表达IL-8，VEGF。45例脑胶质瘤中，27例IL-8呈阳性表达，32例VEGF呈阳性表达，Ⅲ，Ⅳ级脑胶质瘤中IL-8，VEGF的表达比Ⅰ级、Ⅱ级明显增强，IL-8，VEGF评分为强阳性的胶质瘤内MVD明显高于评分为阴性和阳性的MVD（P<0.01）。IL-8表达与MVD呈正相关（rs=0.64，P<0.01）。VEGF表达与MVD之间呈正相关（rs=0.44，P<0.01）。IL-8表达与VEGF表达之间亦呈正相关（rs=0.56，P<0.01）。结论：IL-8，VEGF的表达与胶质瘤病理分级、MVD密切相关，二者在胶质瘤的血管生成中可能相互关联、共同调节肿瘤血管生成。     

原发性中枢神经系统弥漫大B细胞性淋巴瘤16例临床病理分析

目的 探讨原发性中枢神经系统弥漫大B细胞淋巴瘤(diffuse large B-cell lymphomas,DLBCL)的临床病理特点和免疫分子亚型及与预后的相关性.方法 回顾性分析16例原发性中枢神经系统DLBCL的临床表现、影像特点,采用HE染色及EliVision法观察其病理组织学特点和免疫表型特征.结果 临床上主要表现为颅内压增高、肢体乏力、视力障碍和神经精神症状,可为单发或多发性病灶;影像学上,CT示肿块多呈稍低密度阴影,MRI示T1WI呈低或等信号,T2WI呈高或等信号,强化明显,病灶周围常见明显水肿带.组织学特点为瘤细胞细胞形态较单一,弥漫浸润,瘤细胞常围绕血管形成袖套状,伴片状坏死及出血.免疫分子分型示9例DLBCL为生发中心型,7例为非生发中心型.结论 原发性中枢神经系统DLBCL是高度侵袭性淋巴瘤,为2008年WHO淋巴造血系统肿瘤分类已新增加的DLBCL亚型,具有较独特的临床病理学特点及生物学行为.好发中老年人,临床表现和影像学缺乏特异性.病理组织形态特点为瘤细胞弥漫或结节分布,以瘤细胞常围绕血管袖套状浸润为其特征性结构,可有坏死、出血;分子亚型主要为生发中心型.     

HIF-1α在结外鼻型NK/T细胞淋巴瘤血管生成中的作用及意义

目的: 研究缺氧诱导因子-1α(HIF-1α)在结外鼻型NK/T细胞淋巴瘤血管生成中的作用及意义。方法: 采用免疫组化法检测50例人结外鼻型NK/T细胞淋巴瘤中HIF-1α、血管内皮生长因子(VEGF)和血管内皮生长因子受体2(VEGFR2)的表达情况,用CD34单克隆抗体标记血管内皮细胞,并计算肿瘤微血管密度(MVD),用SPSS 13.0软件分析HIF-1α与VEGF、VEGFR2及肿瘤MVD的相关性。结果: (1)50例中有39例(78%)肿瘤细胞HIF-1α阳性,27例(54%)VEGFR2阳性,与淋巴结反应性增生组织中淋巴细胞的表达情况比较均有显著差异(P<0.05);(2)HIF-1α蛋白阳性表达组VEGF和VEGFR2的阳性表达率分别为72%和64%,明显高于HIF-1α蛋白阴性表达组(P<0.05);(3)HIF-1α、VEGFR和VEGFR2蛋白表达与肿瘤MVD相关(P<0.01);(4)15例伴有血管中心性浸润的结外鼻型NK/T细胞淋巴瘤病例均表达HIF-1α。结论: HIF-1α可促进结外鼻型NK/T细胞淋巴瘤肿瘤血管生成,其作用机制可能与VEGF/VEGFR2通路有关。     

人脑胶质瘤中COX-2表达及其与血管新生关系

目的 检测COX-2、VEGF和CD34在人脑胶质瘤中的表达,探讨COX-2、VEGF与胶质瘤微血管密度及血管新生之间的关系及意义.方法 用免疫组化SP法检测80例胶质瘤及10例正常脑组织中COX-2、VEGF和CD34的表达.结果COX-2与VEGF阳性细胞在坏死区周围及血管密集的区域分布密集,80例胶质瘤中二者表达的阳性率分别为68.8%和72.5%,正常脑组织中无表达;COX-2、VEGF的表达与MVD之间成正相关(r=0.927,r=0.939,P<0.05),COX-2与VEGF的表达成正相关(r=0.885,P<0.05),胶质瘤病理级别与COX-2、VEGF、MVD之间均成正相关(r=0.894,r=0.927,r=0.865,P<0.05).结论 COX-2和VEGF在胶质瘤的生长和进展过程中发挥重要作用,与其恶性度关系密切;COX-2可能通过上调VEGF的表达促进肿瘤组织血管新生.     

原发性胸膜上皮样血管肉瘤2例临床病理分析

目的探讨原发性胸膜上皮样血管肉瘤(epithelioid angiosarcoma, EAS)的临床病理学特征、鉴别诊断、治疗及预后。方法收集2例原发性胸膜EAS的临床病理资料,并复习相关文献。结果 2例患者男、女性各1例,年龄分别为47、45岁,均以呼吸系统症状就诊。影像学发现左侧胸膜增厚或包块。镜检见异型上皮样细胞及含红细胞的空泡状瘤细胞,胞质嗜伊红色或透明,胞核圆形空泡状或不规则形,核仁增大,局部见梭形瘤细胞,核分裂象5～12/HPF,坏死多少不等。瘤组织排列呈实性巢片状、条索状、窦隙状脉管样及乳头状。免疫表型:肿瘤细胞vimentin、CD31、ERG弥漫阳性,CD34阴性,Ki-67增殖指数为40%～60%。患者未行放、化疗,均于确诊后短期内死亡。结论原发性胸膜EAS十分罕见,其高度恶性、预后差,临床表现缺乏特征性,易误诊,组织病理学检查可确诊,需与转移癌、恶性间皮瘤、上皮样血管内皮瘤、黑色素瘤及大细胞淋巴瘤鉴别。     

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.     

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.     

'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.     

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.