恶性颗粒细胞癌临床病理,免疫组化和超微结构观察

探讨恶性颗粒细胞瘤的病理学诊断和鉴别诊断要点及组织学起源，方法：对３例恶性颗粒细胞瘤进行临床病理，免疫组化及超微结构观察研究。结果：男性２例，女性１例，平均年龄为４９岁。部位分别为颈部１例，右大腿２例，其中２例分别于术后２年半及７年复发，并伴有区域淋巴结转移。     

颗粒细胞瘤15例临床病理分析

目的探讨颗粒细胞瘤的组织起源及临床病理学特征。方法回顾分析15例颗粒细胞瘤的临床资料及组织学形态特征,并采用免疫组化(SP法)观察其免疫表型。结果良性颗粒细胞瘤13例,恶性颗粒细胞瘤2例。男性5例,女性10例,年龄19~69岁,平均年龄41·6岁,2例恶性颗粒细胞瘤年龄分别为67岁和69岁。良性颗粒细胞瘤直径0·4~5·3cm,平均2·3cm,2例恶性颗粒细胞瘤直径分别为6和14cm。均为单发病例,临床上主要表现为真皮、皮下或黏膜下孤立性无痛性结节,分别位于腰部3例、腋下、胸壁各2例,乳腺、上臂、子宫、肛周、声带、食管、结肠、舌部各1例。病理组织学上,良性颗粒细胞瘤的肿瘤细胞通常有比较丰富的嗜酸性颗粒状胞质和小而深染的胞核,而恶性颗粒细胞瘤的肿瘤细胞中可见带有明显核仁的空泡状核,细胞核明显异型及部分细胞呈梭形。免疫组化示神经标记物NSE、S-100蛋白强阳性,表达溶菌酶的标记物CD68也强阳性,而表达平滑肌和横纹肌的标记物SMA、MG均阴性。结论颗粒细胞瘤为来源于雪旺细胞的肿瘤,恶性者少见,大多发生在年龄大的患者,且肿瘤体积比较大。     

肾恶性横纹肌样瘤15例临床病理及免疫组织化学分析

报道１５例肾恶性横纹肌样瘤（ＭＲＴＫ）的临床病理及免疫组化特点。男女之比为２．８：１。年龄４个月至４岁７个月，平均１岁零６个月。随访１０例，８例均于术后半年内死１０亡，２例健在。典型组织学改变为细胞弥漫排列，多边形，胞浆丰富嗜酸性，核仁突出。部分细胞胞浆内有嗜酸性包涵体，部分病例可见上皮样排列，间质硬化及梭形细胞成分。免疫组化显示１５例Ｖｉｍｅｎｔｉｎ（＋），１２例ＥＭＡ（＋），８例Ｃｙｔｏｋｅｒａｔｉｎ（＋）。结果提示，本瘤是一种好发于婴幼儿、预后差、多表现型的恶性肾肿瘤。可能来源于某种具有双向分化能力的多潜能细胞。     

神经垂体少见肿瘤15例临床病理分析

以光镜、电镜、组化和免疫组化等方法，研究了１５例发生于神经垂体（包括漏斗突、漏斗柄和正中隆起）的少见肿瘤：星形细胞瘤１２例（其中３例伴垂体腺瘤、１例伴灶性节细胞增生）；节细胞瘤２例（１例伴侵袭性垂体腺瘤）；颗粒细胞瘤１例。临床均有闭经泌乳等内分泌症状和视力改变及内分泌检验异常等。因瘤体多较小，且质地稀软，临床、手术、放射和病理检查常被忽视。手术疗效佳，术后短期内症状体征消失或明显改善。此外，还探讨了节细胞瘤和颗粒细胞瘤的起源，讨论了临床、手术、放射和病理检查等应注意的问题等。     

恶性颗粒细胞瘤10例临床病理学观察及文献复习

目的 探讨恶性颗粒细胞瘤的临床病理学特征,评价组织学上诊断恶性的标准。方法 对10例恶性颗粒细胞瘤的临床资料和组织学形态进行回顾性分析,并采用免疫组织化学(LSAB法)和电镜检测研究其免疫表型和超微结构。结果男性4例,女性6例,年龄范围为27～73岁(平均46岁)。临床上,9例表现为皮下或深部软组织内无痛性生长的孤立性肿块,其中1例伴有周围神经症状。肿瘤位于下肢3例,乳腺2例,项部2例,胸壁、右颈部和盆腔者各1例。肿瘤直径2～11cm,平均4．8cm。镜下由成巢或成片的多边形细胞组成,胞质呈嗜伊红色颗粒状,与良性性颗粒细胞瘤极为相似,但仔细观察发现,9例显示至少下述形态中的3种：核增大呈空泡状并可见明显的核仁;多形性瘤细胞;核质比增大;瘤细胞趋向梭形;可见核分裂象;凝固性坏死。除经典性形态外,1例尚可见散在的多核性瘤细胞。余1例除局部区域显示核增大呈空泡状并可见明显的核仁外,其余形态均不明显,但临床上却呈恶性经过。9例均强阳性表达S-100蛋白和神经元特异性烯醇化酶(NSE),7例尚表达CD68。电镜观察显示瘤细胞胞质内充满大量退变的复合性溶酶体。随访7例,5例复发,4例转移,2例死于肿瘤。结论 (1)Fangburg-Smith等的组织学恶性标准具有较高的可重复性,但在少数情形下,最终诊断仍需结合肿瘤的生物学行为;(2)提议将核分裂象的标准修订为＞5／50HPF;(3)广泛性局部切除加上必要的区域淋巴结清扫仍是目前最主要的治疗手段,辅助性化疗和(或)放疗并不能明显改善患者的预后;(4)描述一种尚未见报道的多核性瘤细胞形态亚型。     

良、恶性颗粒细胞瘤15例临床病理分析

目的探讨良、恶性颗粒细胞瘤的临床病理学特征及其诊断标准。方法回顾性分析15例颗粒细胞瘤(含1例恶性颗粒细胞瘤)的临床资料、病理学特征及免疫表型,并复习相关文献。结果 15例中女性14例,男性1例,年龄18～66岁,平均42岁。14例为皮下或软组织内无痛性生长的孤立性肿块,1例(组织学诊断为恶性颗粒细胞瘤)表现疼痛及关节活动受限,伴复发、转移。肿瘤位置:四肢4例,乳腺2例,舌部2例,眼眶2例,咽喉部2例,颈枕部、升结肠和外阴各1例。肿瘤直径0. 3～4. 5 cm,平均2. 4 cm。1例镜下见凝固性坏死、核增大呈空泡状并可见明显的核仁、多形性、高核质比、瘤细胞梭形变和核分裂。形态学上,15例采用Fangburg-Smith等提出的6项诊断标准判断,结果显示:良性颗粒细胞瘤11例、不典型颗粒细胞瘤3例、恶性颗粒细胞瘤1例。14例有完整随访资料,13例无复发,1例复发3次并转移。结论颗粒细胞瘤少见,恶性颗粒细胞瘤尤其罕见,在日常工作中应高度警惕是否为恶性,以避免漏诊。Fangburg-Smith等提出的诊断标准在实际工作中有较好的可操作性。且与该肿瘤的生物学行为之间有较好的相关性,有利于临床医师对患者进行合理处置。     

上皮样型恶性周围神经鞘瘤

我们拟探讨上皮样型恶性周围神经鞘瘤形态学特征与预后的关系。１２例经光镜和免疫组化观察，其中７例作了电镜观察。组织学可分为纯上皮样型（５例）；混合型、伴有梭形细胞区（５例）和骨化型（２例）。１２例均呈Ｓ－１００蛋白阳性表达，并显示多种细胞骨架异质性，包括（１）神经细胞分化：表现为ＮＳＥ和神经微丝阳性反应，节细胞分化；（２）上皮性分化：角蛋白阳性反应，电镜见有桥粒和张力微丝束；（３）间叶性分化：波形蛋白阳性、骨化生和横纹肌样表型。该瘤的异质性与侵袭性同步，异质性明显的３例均因肺转移死于就诊后７个月至４年。     

嗅神经母细胞瘤的光镜、电镜和免疫组织化学观察

报道了１１例嗅神经母细胞瘤的光镜、免疫组化及其中２例超微结构观察结果。１１例嗅神经母细胞瘤中１０例可见瘤细胞排列成大小不等的巢状或条索状；８例有Ｈｏｍｅｒ－Ｗｒｉｇｈｔ菊形团，５例见Ｆｌｅｎｅｒ菊形团（其中４例同时伴有Ｈｏｍｅｒ－Ｗｒｉｇｈｔ菊形团）；８例可见瘤细胞之间由细胞突起形成的嗜酸性纤维样背景。电镜下１例瘤细胞内见神经原纤维，２例均有神经内分泌颗粒，并对其颗粒进行了形态测量。多种抗体免疫组化染色：ＮＳＥ１１例均为阳性，Ｖｉｍｅｎｔｉｎ，Ｓ－１００、Ｋｅｒａｔｉｎ各有４例、３例和１例阳性，ＮＦ，ＥＭＡ，ＣＥＡ，ＬＣＡ均为阴性。文中对嗅神经母细胞瘤的病理形态及免疫组化特征在诊断中的意义进行了讨论。     

膀胱炎性假瘤—假肉瘤性肌纤维母细胞增生

目的：探讨膀胱炎性假瘤的病理学特征。方法：描述4例膀胱炎性假瘤的临床病理及免疫组化特征并复习有关文献。结果：男女各2例患者,年龄分别为36,27,36,8岁,肿瘤直径分别为3,4,3及5cm,主要临床症状为肉眼血尿或排尿困难,组织学检查：肿瘤主要成分为梭形细胞,胞质嗜酸性,有大的卵圆形至梭形泡状核,有1－2个明显的核仁,分裂象少见,无不典型核分裂,3例免疫表型,3例Vim呈弥漫阳性;α-SMA（2例）及MSA（1例）局部少数细胞阳性;2例AE1／AE3多数细胞呈阳性,Des,Myo及EMA均阴性。3例术后分别随访40,16,14个月无复发,1例为近期病例,结论：病损为一种良性,非肿瘤性肌纤维母细胞增殖,要避免误诊为恶性。     

混合性节细胞瘤/垂体腺瘤4例临床病理观察

目的探讨混合性节细胞瘤／垂体腺瘤发生机制、临床病理特征、诊断及鉴别诊断。方法复习4例混合性节细胞瘤／垂体腺瘤患者的临床资料，并对其进行组织学观察和免疫组化（EnVision—plus法）标记。结果4例混合性节细胞瘤／垂体腺瘤患者均为女性，年龄10～35岁，平均26．5岁。临床上3例表现内分泌症状，1例有癫痫症状。组织学上肿瘤由两种不同成分组成，一种结构主要由较多神经节细胞组成，节细胞体积大，可见圆形的尼氏小体，核大，核仁突出，免疫组化标记瘤细胞表达CgA、Syn、S-100蛋白，不表达GFAP；另一部分腺瘤细胞大小形态较一致，圆形或卵圆形，胞质丰富，嗜酸性或空淡，间质血窦丰富，瘤细胞表达GH和PRL。结论混合性节细胞瘤／垂体腺瘤是蝶鞍区极少见的肿瘤，好发于青年女性，常合并肢端肥大症。该瘤的诊断主要依靠组织病理学，并辅以免疫组化标记。治疗主要采用单纯手术切除，预后较好。     

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.     

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.     

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.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

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.