原发性肺隐球菌病的病理诊断和超微结构观察

目的探讨原发性肺隐球菌病(PC)的病理诊断和超微结构特点。方法对27例PC的临床病理资料进行回顾性分析、组织化学染色和光镜观察,12例进行透射电镜观察。结果27例中,2例肺穿刺活检明确诊断,25例开胸探查,胶样病变2例,非干酪性肉芽肿病变25例,均检出新型隐球菌(CN)。黏液卡红(MC)、过碘酸雪夫染色(PAS)、奥尔辛蓝(AB)和Grocott六胺银(GMS)染色隐球菌的检出率分别为87．0％(20／23)、100％(27／27)、66．7％(18／27)和100％(23／23)。透射电镜观察,CN均有荚膜形成,大部分结构简单,细胞器不发达,细胞退变;部分隐球菌有细胞核、核仁、线粒体和空泡;CN的检出率为91．7％(11／12)。结论PC的临床表现和影像学缺乏特征性,穿刺或开胸肺活检仍然是PC诊断的主要手段。光镜结合电镜观察以及MC、GMS和PAS组织化学染色,能对PC做出明确诊断及鉴别诊断。     

肺隐球菌病25例临床病理分析

目的探讨肺隐球菌病(PC)的临床和病理特征及其鉴别诊断。方法对25例PC手术标本进行常规HE染色及淀粉酶消化后过碘酸雪夫(D-PAS)、黏液卡红(MC)和Gorcott六胺银(GMS)特殊染色,观察PC在组织中的形态特点,并结合相关文献进行讨论。结果25例中,男16例,女9例,年龄18～52岁,平均36岁。人类免疫缺陷病毒抗体(HIV-Ab)阳性3例。胸部影像学检查:18例表现为单发或多发肺部结节,7例表现为片状实变影。25例均经胸腔镜活检手术切除,病理检查确诊。HE染色:多核巨细胞内外见大量淡蓝色圆形或卵圆形隐球菌菌体,具有折光性强的胶样荚膜;D-PAS、MC及GMS特殊染色:隐球菌菌体呈紫红色、鲜红色和黑色,更清晰。结论PC多由新型隐球菌引起,其临床及影像学表现缺乏特异性,易误诊和漏诊;组织病理学检查及特殊染色,PC具有典型的形态结构,是确诊本病的重要手段。     

新生隐球菌格鲁比变种表型变异菌株的基因及毒力对比研究

新生隐球菌(Cryptococcus neoformans)属于真菌界担子菌门隐球菌属,是临床上的致病真菌,可致器官移植等免疫抑制患者发生新生隐球菌病,与艾滋病有一定相关.宽大的荚膜是其典型形态学特征及临床分离鉴定的重要依据,我们在实验中对获赠自日本千叶大学医学部真菌研究所的新生隐球菌进行传代培养时发现有2株菌(IFM56803和IFM56743)发生了显著的表型变异,出现光滑型(SM)及黏液型(MC)两种不同的菌落,荚膜形态也出现明显差异,墨汁染色发现MC株的隐球菌荚膜较SM株的厚4～5倍.     

新生隐球菌墨汁染色检查实验的改进

目的为消除生物安全隐患,让学生能安全高效地完成新生隐球菌墨汁染色检查实验。方法分别用10％EP醛或56℃水浴5rain对腹腔液、脑脊液中的新生隐球菌进行灭活处理,使其不再具有活性和致病性,镜下观察其形态的改变。结果用10％甲醛处理过的新生隐球菌,其荚膜形态已不能观察,而经56℃水浴灭活的新生隐球菌,其荚膜形态没有发生变化。结论新生隐球菌腹腔液或脑脊液采用56℃水浴5min即可灭活而不影响其荚膜形态,为学生安全高效地完成新生隐球菌墨汁染色检查实验提供了条件。     

肺隐球菌病37例临床病理分析

目的探讨肺隐球菌病的临床病理特征、诊断及鉴别诊断。方法收集安徽省胸科医院37例确诊为肺隐球菌病组织标本,对其临床病理特征、HE及特殊染色等进行回顾性分析,并复习相关文献。结果37例肺隐球菌病中男性20例,女性17例,年龄12~80岁,中位年龄45岁。常见临床症状有咳嗽、咳痰、胸痛,部分重症患者有慢性病或激素治疗史,另有15例患者无症状。常见胸部影像学表现有结节影18例,团块状、片状影19例,混合病变10例。4例行乳胶凝集试验检测均阳性,37例行六胺银染色均阳性。结论肺隐球菌病好发于青壮年,多数患者无免疫功能受损;临床及影像学表现无特异性;多数病例通过组织病理学确诊,六胺银等特殊染色有助于病理诊断;乳胶凝集试验可作为肺隐球菌病的首选辅助诊断手段。     

黏液卡红复染在诊断艾滋病合并隐球菌脑膜炎中的应用

目的 探讨黏液卡红复染在诊断艾滋病合并隐球菌脑膜炎(cryptococcal meningitis, CM)中的应用价值。方法 采用黏液卡红复染法检测75例艾滋病脑脊液细胞涂片,分析黏液卡红复染法、真菌培养、墨汁染色和隐球菌荚膜抗原检测四种检查方法诊断CM的敏感性和特异性。结果 脑脊液细胞涂片黏液卡红复染背景干净,隐球菌荚膜呈红色,同脱落细胞和其他微生物易鉴别。脑脊液黏液卡红复染法、真菌培养和墨汁染色诊断CM的敏感性分别为94.4%、77.8%和11.1%;特异性均为100%。其中65例的脑脊液隐球菌荚膜抗原检测敏感性为96.2%,特异性为100%。黏液卡红复染法与真菌培养和隐球菌荚膜抗原检测相比,差异无统计学意义(P>0.05);同墨汁染色相比,差异有统计学意义(P<0.005)。结论 脑脊液细胞涂片黏液卡红复染法诊断艾滋病合并CM具有高敏感性和特异性,为临床提供微生物诊断依据。     

肺隐球菌病漏诊原因分析

目的 探讨病理(含术中冷冻切片)漏诊肺隐球菌病(pulmonary cryptococcosis,PC)的原因,以提高病理诊断水平.方法 回顾7例PC的临床、病理资料及其病理诊断过程.结果 7例PC中有5例病理漏诊:(1)3例活检常规石蜡切片分别初诊为"脂质肉芽肿"、"纤维肉芽组织"和"慢性炎症";1例术中冷冻切片"考虑为结核病",冷冻切片检查后相应石蜡切片改诊为"肺隐球菌病";另1例术中冷冻切片诊为"结节病",相应石蜡切片仍误诊为"结节病".(2)病理漏诊的5例PC中,4例皆被及时纠正,得以正确治疗;1例术中冷冻切片及其常规石蜡切片皆被诊为"结节病"并于2个月后继发隐球菌性脑膜炎.结论 病理漏诊PC的原因:①未虑及肉芽肿形态的多样性及其可能的病因相关性;②未将PC列入病理鉴别诊断思路;③观察镜下病变不仔细、忽视微细病变的诊断提示意义.术中冷冻切片可及时诊断PC,有助于避免过度治疗.需重视结节病与结核病、隐球菌病等感染性肉芽肿的病理鉴别诊断,应慎诊结节病.     

新生隐球菌荚膜基因CAP60与荧光蛋白融合表达系统的构建

荚膜是新生隐球菌的主要毒性因子 ,目前Ｃｈａｎｇ等已克隆了 4种荚膜基因 :ＣＡＰ5 9、ＣＡＰ6 4、ＣＡＰ6 0及ＣＡＰ10。已知这 4种基因对新生隐球菌的荚膜形成都是必须的 ,缺失任何一个基因都会使新生隐球菌变成无荚膜表型。搞清荚膜形成的任何一个生理、生化机制都将在新生隐球菌的临床诊断和治疗上带来突破性的进展。我们建立荧光蛋白作为标记与荚膜基因ＣＡＰ6 0融合表达 ,为进一步的研究创造条件。根据已知的ＣＡＰ6 0基因序列设计ＰＣＲ引物 ,上游为 5′ ＡＴＴＧＣＴＡＧＣＴＴＣＧＡ ＣＡＧＡＣＡＴＴＧＡＧＣＣＣＴ 3′ ,下游引…     

肺原发性恶性外周神经鞘瘤的临床病理分析

目的 探讨肺脏原发性恶性外周神经鞘瘤(MPNST)的临床病理学特征及诊断、鉴别诊断要点。方法 对2例肺MPNST进行临床病理学分析及免疫组织化学与超微结构研究。结果 2例光镜下均显示MPNST的形态特点，免疫组织化学显示S-100蛋白、MBP、Vim、NSE肿瘤细胞呈阳性表达，电镜观察1例可见特征性Luse小体。结论 肺原发性MPNST极为罕见，临床诊断较困难。根据其光镜病理形态特征，S-100蛋白、MBP免疫组织化学检测和(或)电镜检查可确诊。结合文献，该肿瘤早期无明显临床症状，一般发现时已属晚期，预后差。病理学上应与肺脏平滑肌肉瘤、纤维肉瘤、单相型滑膜肉瘤、肉瘤样癌鉴别。     

移植肾新型隐球菌感染1例报道及文献复习

目的探讨移植肾新型隐球菌感染的临床病理特征,以便更好地预防该病。方法对1例移植肾新型隐球菌感染病例进行临床病理分析,并复习相关文献。结果该例患者于肾移植术后10天发热,痰、血液、尿培养均提示白色念珠菌感染。肾活检结果示肾组织隐球菌感染性肉芽肿,伴微小脓肿形成;隐球菌荚膜呈IgA和IgM线状弥漫性阳性。结论对于肾移植术后新型隐球菌感染的危险因素及其预防和控制,仍需进一步探索。监控患者手术前后血清抗隐球菌特异性抗体及免疫相关细胞因子的水平可能对于早期发现隐球菌感染有一定帮助。     

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.     

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.