SA-30诱导的小鼠子宫内诱导型一氧化氮合酶的变化

目的　检测精子膜抗原 SA- 30对小鼠子宫内诱导型一氧化氮合酶 (i NOS)含量及分布的影响 ,从而了解 SA - 30的抗生育机制。　方法　 SA- 30免疫雌性昆明小鼠后 ,应用免疫组织化学方法 ,对子宫内的 i NOS进行了检测。结果　 SA - 30免疫后对间情期小鼠子宫内的 i NOS没有明显影响 ,无论是免疫组还是对照组 ,在子宫内膜基质中均有大量阳性细胞分布 ,两者无明显差异 ;在妊娠第 3d时 ,对照组的小鼠子宫中有较多 i NOS表达 ,阳性标记主要集中在内膜上皮及固有膜中的子宫腺上 ,经 SA- 30免疫的小鼠子宫中 ,i NOS表达则显著减少 ,整个内膜标记极弱 ,只在子宫肌层内有少量 i NOS阳性细胞分布。　结论　 SA - 30可能通过使妊娠早期小鼠子宫内 i NOS表达显著减少 ,而影响小鼠胚胎植入及早期胚胎的发育     

阻断交感神经对小鼠胚胎植入和子宫局部免疫的影响

目的探究交感神经对小鼠妊娠早期胚胎发育作用的机制。方法利用组织学、免疫组织化学和酶联免疫吸附（ELISA）方法观察化学阻断剂6．羟多巴胺（6．OHDA）损毁交感神经对小鼠妊娠早期子宫局部免疫水平和早期胚胎发育的影响。结果化学损毁交感神经后，小鼠受孕率下降，胚胎植入数减少约64．4％；妊娠鼠子宫内膜固有层不发达，微血管分布少；子宫CD4^＋T细胞略有增多，而CD8^＋T细胞明显增加，特别在E3和E5，与对照组比较差异极显著（P〈0．01）；细胞因子IL-2含量升高，尤其E5升高最明显，达3．6倍，而IL-4含量仅在E5有明显升高，1L-2，1L-4比值显著升高。结论交感神经对孕小鼠子宫内膜组织学结构和子宫CD4^＋／CD8^＋T细胞与Th1／Th2细胞比值的影响可能是调控胚胎植入和早期发育的机制之一。     

CD57+自然杀伤细胞在妊娠早期小鼠子宫壁内的分布

目的　探索ＣＤ５７＋ 自然杀伤细胞（ＮＫ细胞,ｎａｔｕｒａｌｋｉｌｌｅｒｃｅｌｌｓ）在小鼠妊娠早期子宫壁内的意义。方法　用小鼠抗人ＮＫ细胞ＣＤ５７单克隆抗体,对未经产小鼠妊娠早期子宫壁内ＮＫ细胞进行免疫组织化学标记。结果　孕０ｄ,小鼠子宫壁内见少量ＣＤ５７＋ 细胞,孕２ｄ 时ＮＫ细胞数量剧增,孕４ｄ 时稍下降。孕６ｄ、孕８ｄ 时数量更少（低于０ｄ 值）。孕６ｄ 和８ｄ 均出现妊娠失败个体,其子宫壁内ＮＫ细胞很多,显著高于正常妊娠６ｄ 和８ｄ 小鼠的数量（Ｐ＜ ０．０１）。从分布区域看,胚胎着床（４．５ｄ）前,ＮＫ细胞多位于子宫肌层,胚胎着床后仅存在于着床点以外的子宫内膜和肌层。在妊娠失败个体,ＮＫ细胞广泛存在于子宫内膜和肌层中。　结论　小鼠交配后子宫ＮＫ细胞增多与子宫炎性反应有关。着床期以后子宫ＮＫ 细胞增多与妊娠失败有一定的相关性。     

CD3^—CD4^—CD8^＋小鼠胸腺细胞表型的研究

目的 分析CD3^－CD4^－CD8^＋胸腺细胞的表型特征,阐明其在胸腺发育中所处地位。方法 分离纯化小鼠CD4^－CD8^＋单阳性胸腺细胞,进行CD3与其他表面标志的染色,然后进行FACS分析。结果 CD3^－CD4^－CD8^＋细胞体积较大,对可的松敏感,TGRαβ阴笥,高度表达不成熟标志6C10和HSA,不表达活化标志CD69和成熟标志Qa-2。结论 CD4^－CD8^＋单阳性胸腺细胞可明显分为CD3^＋和CD3^－两个亚群,后者代表了胸腺发育过程中由CD4^－CD8^－双阴性细胞向CD4^＋CD8^＋双阳性细胞转变的过渡状态。     

乙肝病毒核心抗原DNA疫苗诱导小鼠抗原特异性CD8+T细胞动态变化和动态分布

目的：研究乙肝病毒核心抗原(HBcAg)DNA疫苗诱导的细胞免疫应答。方法：用表达乙肝病毒核心抗原N端144个氨基酸的重组质粒DNA(简称pHBc144)100ug免疫C57BL／6小鼠，用细胞内细胞因子染色技术检测小鼠体内抗原特异性CD8^ T细胞的动态变化。结果：pHBc144免疫后抗原特异性CD8^ T细胞逐渐增多，在初次免疫的第14天出现第一个免疫应答高峰，此后抗原特异性CD8^ T细胞数量逐渐下降进入免疫记忆期并在1年内维持在稳定水平。加强免疫后在第10天抗原特异性CD8^ T细胞数量达到高峰，约是初次免疫应答高峰的2倍，此后抗原特异性CD8^ T细胞数量逐渐下降，但下降的速度比初次免疫应答减缓。结论：pHBc144DNA疫苗可诱导有效的细胞免疫应答。     

妊娠早期小鼠子宫巨噬细胞分布和活性的变化

目的:通过研究妊娠早期子宫CD14+巨噬细胞数量、分布及酸性磷酸酶(ACP)活性变化,探讨巨噬细胞与母胎免疫耐受的关系.方法:用免疫组织化学方法和酶细胞化学研究小鼠妊娠早期子宫CD14+巨噬细胞及ACP的变化.结果:对照组CD14+巨噬细胞主要分布在子宫内膜.小鼠妊娠后内膜中数目减少,第3日最少;肌膜和外膜巨噬细胞增加,第2日达到高峰.CD14免疫反应阳性面积变化趋势与此类似.第3～5日期间ACP的活性下降并维持在较低的水平.结论:巨噬细胞在着床期抗原识别和处理能力受到了抑制,参与了妊娠早期母胎免疫耐受的形成.     

交感神经对兔子宫内CD4＋T淋巴细胞分布和早期胚胎发育的影响

目的:手术切断支配兔子宫的交感神经后,观察其对子宫局部免疫状况和早期胚胎发育的影响.方法:使用H-E染色和免疫组织化学的方法观测子官内膜形态及CD4 T淋巴细胞数量及分布.结果:切断交感神经后,兔受孕率下降,胚胎着床数减少约61%,早期胚胎发育迟缓,甚至有死胚现象.组织学观察显示切断交感神经的妊娠兔子官内膜固有层不发达,明显未发育到适应胚泡着床的状态;子宫内CD4 T淋巴细胞发生了重新分布,肌层和非妊娠部位子官内膜的CD4 T淋巴细胞分布增多,而妊娠部位子宫内膜的CD4 T淋巴细胞数量减少.结论:交感神经通过调节子宫内膜组织学变化和子宫内CD4 T淋巴细胞的数量及分布,从而影响胚胎着床和早期发育.     

SARS-CoV S DNA疫苗诱导特异性T细胞及相关细胞因子的特性研究

目的 小鼠经皮下SARS-CoV S DNA疫苗免疫后，研究其特异性T细胞及相关细胞因子的特性。方法SARS-CoV S DNA疫苗免疫BALB／c小鼠后，获取淋巴细胞悬液。经S抗原多肽刺激后，采用ELISA检测细胞培养上清液中IFN-γ／的水平，利用流式细胞仪在单个细胞水平上检测IFN-γ和IL-2的表达及其关系。结果 当S混合多肽刺激后，DNA疫苗免疫小鼠的淋巴细胞产生大量的IFN-γ，与对照鼠相比差异有统计学意义（P〈0．01）。细胞亚群分析的结果表明，IFN-γ^＋和IL-2^＋的CD4^＋T细胞百分率明显高于CD8^＋T细胞。单独产生IL-2的细胞占大多数，其次为IFN-γ和IL-2双阳性细胞，只产生IFN-γ的细胞很少。结论 SARS-CoV S DNA疫苗免疫小鼠后可以诱导抗原特异性CD4^＋和CD8^＋T细胞的产生。     

孕酮拮抗物RU486对妊娠小鼠子宫巨噬细胞的影响及与妊娠相关性的研究

目的　研究孕酮拮抗物RU4 86对妊娠小鼠子宫巨噬细胞的影响及与妊娠的相关性。　方法　取孕4、10d的小鼠 ,皮下注射RU4 86 (每只 15 0mg L) ,对照组以等量生理盐水代替。在注射后 12、2 4、36h密切观察妊娠结果 ,并用免疫组织化学方法检测子宫内的巨噬细胞。　结果　孕 4d ,注射RU4 86可以完全阻止胚泡的着床 ,且注射后 12～ 36h有大量的巨噬细胞涌入子宫内膜、肌层和肌间血管层 ,细胞数量极显著地高于对照组 (P <0 0 0 1)。孕 10d ,RU4 86处理可以导致大多数胚胎吸收 ,并在处理后 4～ 36h子宫巨噬细胞的数量和分布发生急剧的变化 ,尤其是 12～ 36h细胞数量极显著地高于对照组 (P <0 0 0 1)。　结论　RU4 86诱导小鼠妊娠早期的着床失败和妊娠中期的胚胎吸收与大量巨噬细胞侵入子宫有密切的关系 ,拮抗孕酮的免疫抑制功能可能是RU4 86的抗孕机制之一     

妊娠早期小鼠卵巢、输卵管及子宫内诱导型一氧化氮合酶的分布

目的　了解胚泡着床前后妊娠昆明系小鼠卵巢、输卵管及子宫内诱导型一氧化氮合酶 (inducible ni-tric oxide synthase,i NOS)的分布。　方法　免疫细胞化学 L SAB法。　结果　妊娠 2～ 5 d小鼠的卵巢内 ,黄体细胞上有 i NOS的阳性表达 ;输卵管粘膜上有 i NOS的分布 ,肌层则为阴性 ;妊娠 2、3d的小鼠子宫内 ,阳性标记主要出现在子宫内膜上皮以及子宫内膜中的子宫腺上皮 ,内膜基质细胞为阴性 ;妊娠 4d的子宫内 ,子宫腺及蜕膜部分均有 i-NOS的分布 ,妊娠 5 d时 ,在小鼠胚泡的表面也检测到了 i NOS的存在。　结论　小鼠胚泡着床前后 ,在其卵巢、输卵管及子宫内均有 i NOS的存在 ,提示 i NOS在小鼠胚胎早期发育及着床过程中起作用。     

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.